The Cost-Effectiveness of Behavioral Health Interventions

Best Practices in the Behavioral Management of Chronic Disease: Volume IV

Supriya Misra, M.A. and Jodie A. Trafton, Ph.D.

Published by: Institute for Disease Management

A Division of Institute for Brain Potential

Best Practices in the Behavioral Management of Chronic Disease: Volume IV

The Cost-Effectiveness of Behavioral Health Interventions

Supriya Misra, M.A. & Jodie A. Trafton, Ph.D.

Published by: Institute for Disease Management

A Division of Institute for Brain Potential

1 ABOUT THE AUTHORS

Supriya Misra, M.A. is a doctoral candidate at the Harvard T.H. Chan School of Public Health. She received her graduate and undergraduate degrees in Psychology, with a focus in Neuroscience, at Stanford University, and has years of management and research experience in the development and implementation of evidence-based health education and health technology to promote behavior change for both communicable and non-communicable diseases.

Jodie A. Trafton, Ph.D. is Director of the Program Evaluation and Resource Center for the Veterans Health Administration’s National Office of Mental Health Operations. She also trains graduate and post-doctoral researchers and mental health professionals as an affiliated Clinical Associate Professor at Stanford Medical School Department of Psychiatry and Behavioral Sciences and the Center for Health Policy, and is Director of Publications at Institute for Brain Potential.

Dr. Trafton is responsible for development of data-based management systems for mental health programs in the Veterans Health Administrations 141 health care systems, which together constitute one of the largest integrated mental health care systems in the world. These management systems include (1) performance measurement systems, (2) business intelligence systems for strategic capacity planning, productivity management, monitoring staff and patient satisfaction, and ensuring timely local availability of evidence-based clinical programming in alignment with enrollees’ clinical needs, (3) clinical quality management and decision support tools to track alignment of clinical practice patterns with guideline recommended care, and identify patients who might benefit from changes in treatment plan or additional services, (4) technical assistance programs that engage challenged mental health programs in problem- solving and action planning, train program managers and clinicians in data interpretation and use, and foster sharing of best practices, and (5) implementation and evaluation of innovative pilot programs to address emergent health care delivery challenges. The management systems enable decision-making at the patient, provider, clinic manager, and hospital management level to continually improve access to effective, high quality mental health services for Veterans across the United States.

Here, the authors have applied their knowledge and experience to develop this text, concisely but thoroughly presenting the evidence-base for cost-effectiveness of behavioral and mental health interventions to guide health care managers in design of clinical and cost-effective services.

Acknowledgements:

We would like to acknowledge the editorial assistance of Linda Worsley and Austin Frakt, Ph.D.

Supriya Misra, M.A. and Jodie A. Trafton, Ph.D.

This book is not intended as a substitute for the medical recommendation of physicians or other healthcare providers. Neither the authors nor the publisher shall be liable or responsible for any health, welfare or subsequent damage allegedly arising from the use of any information contained in this book.

All guidelines and discussions are presented as examples or generalized information only and should never be used as the basis for a legal document. They are intended as resources that can be selectively used and adapted with the advice of legal, medical and education resources to meet state, local and individual school district and specific departmental needs and requirements.

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Library of Congress Cataloging-in-Publication Data Best Practices in the Behavioral Management of Chronic Disease: Volume IV: The Cost Effectiveness of Behavioral Health Interventions ISBN: 978-0-9832465-4-1 Library of Congress Control Number: 2016953253

Institute for Brain Potential (IBP) is a non-profit organization dedicated to providing advances in Behavioral Medicine through publications and conferences. IBP is a 501(c)(3) organization (tax identification number 77-0026830) founded in 1984 as Institute for Cortext Research and Development. The Institute has trained over one million health professionals in the neurobehavioral sciences and has published books in the fields of Neuropsychology and Behavioral Medicine including the three-volume series, Best Practices in the Behavioral Management of Chronic Disease.

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BEST PRACTICES IN THE BEHAVIORAL MANAGEMENT OF CHRONIC DISEASE: VOLUME IV

THE COST EFFECTIVENESS OF BEHAVIORAL HEALTH INTERVENTIONS

Preface: UNDERSTANDING COST-EFFECTIVENESS RESEARCH 1 Recommendations for the General Reader 12 Glossary of Common Abbreviations in the Tables 19

PART 1: NEUROPSYCHIATRIC CONDITIONS Chapter 1: ANXIETY DISORDERS 22 Chapter 2: DEPRESSIVE DISORDERS 67 Supplement: GENERAL MENTAL HEALTH PROBLEMS 126 Chapter 3: BIPOLAR DISORDERS 136 Chapter 4: SCHIZOPHRENIC SPECTRUM DISORDERS 145 Chapter 5: PERSONALITY DISORDERS 164 Chapter 6: DELIBERATE SELF-HARM 181 Chapter 7: EATING DISORDERS 194 Chapter 8: ALCOHOL USE 208 Chapter 9: TOBACCO USE 233 Chapter 10: ILLICIT DRUG USE 250 Chapter 11: DISRUPTIVE BEHAVIOR DISORDERS IN YOUTH 267

PART 2: BEHAVIORAL MEDICINE Chapter 12: LIFESTYLE INTERVENTIONS FOR HEALTHY WEIGHT 287 Chapter 13: LIFESTYLE INTERVENTIONS FOR METABOLIC SYNDROME 309 Chapter 14: SLEEP DISORDERS 326 Chapter 15: CHRONIC SOMATIC SYMPTOMS 337 Chapter 16: CHRONIC PAIN 357 Chapter 17: DEMENTIA 388 Chapter 18: END-OF-LIFE CARE 402 Chapter 19: OTHER SELECTED MEDICAL DISORDERS 421

Epilogue: PROMISING HEALTHCARE DELIVERY SYSTEMS 436

Preface

PREFACE: UNDERSTANDING COST-EFFECTIVENESS RESEARCH

INTRODUCTION This unique text is designed as a practical guide for health care professionals and decision-makers who develop, implement or evaluate treatments that incorporate behavioral health interventions. This information can appear dense at first, but we hope this introduction will convince you why cost-effectiveness is so vital, and provide a comprehensible guide for how to interpret the findings summarized in this book. We strongly encourage all readers to read the section, “Recommendations for the General Reader” for handy tips on how to prioritize and digest the most relevant information for your specific needs.

In the last decade, a revolution has occurred in the understanding and application of behavioral health for a wide spectrum of chronic conditions. Yet the majority of health care providers have not yet integrated behavioral interventions into their health care delivery systems. This text summarizes current knowledge from cost-effectiveness trials to reveal which behavioral health interventions can reduce costs and improve quality of life. To our knowledge, this text is the first of its kind to provide a systematic and detailed review of the economic benefits of behavioral health interventions.

Increased life expectancy coupled with finite health care spending has made the cost-effective prevention and management of chronic conditions an urgent need. Individuals with one chronic condition incur double the health care costs of those with none. Multiple chronic conditions are increasingly common, exceeding 65% in the growing elderly population (65 years and older; Lehnert et al., 2011). In addition to significantly worse health outcomes, multiple chronic conditions also skyrocket costs: patients with multiple conditions cost up to seven times as much as those with only one chronic condition (Stanton et al., 2005).

U.S. Health Care Spending The United States has the highest health care spending per capita of any developed country, without better health outcomes. Health care spending has risen from 9% of the U.S. economy in 1980 to 17.4% in 2013, now totaling almost $3 trillion. Some of this increased spending is due to aging of the population and a shift in medical focus from infectious to chronic disease. However, some is due to increased demand for and use of advanced technologies and newer prescription medications, where lower cost solutions could be similarly effective. Projections estimate that health care spending will continue to increase by an average of 5.7% per year, outpacing the estimated growth in GDP at 4.6%. At these rates, health care will total 19.3% of the U.S. economy by 2023 (Centers for Medicare and Medicaid Services, 2013).

Almost 50% of the population has at least one chronic condition, contributing to 84% of U.S. health care spending (Anderson, 2010). While only about 25% of the population is over the age of 55, those over 55 account for over 50% of U.S. health care spending. As we will discuss in further detail, these estimates only account for the direct costs on the health care system and not the equally significant

1 Preface indirect or intangible costs experienced by patients, their families, and society at large. As one example, beyond health care costs, serious mental illnesses were estimated to contribute to a loss of $193.2 billion in personal earnings as of 2002, most notably due to the impaired functioning that results from such disorders (Kessler et al., 2008).

Remarkably, 1% of the population accounts for 23% of health care spending and 5% of the population accounts for 49% of spending. These findings, illustrated in Figure 1, highlight the immediate need for targeted behavioral interventions. For example, patients at risk for multiple chronic conditions, such as metabolic syndrome disorders, will incur high treatment costs without effective prevention and management.

97% 100%

90% 82% 80% 76% 70% 66% 60% 50% 50% 40%

30% 23% 20%

10% 3% 0% Top 1% of Top 5% Top 10% Top 15% Top 20% Top 50% Lower health 50% spenders *Peterson-Kaiser Health System Tracker (2016).

The five most expensive disorders in 2002 were heart conditions (8.3% of total health care spending), trauma (6.9%), cancer (6.0%), neuropsychiatric disorders (5.9%), and pulmonary conditions (5.6%), accounting for almost a third of total health care spending. Meanwhile, a quarter of the population had one or more of the five most common disorders (mood disorders, diabetes, heart disease, asthma, and hypertension), for which treatment costs were $62.3 billion in 1996. More notably, total costs for people with one or more of these disorders were much higher, at $270 billion or 49% of total health care costs (Stanton et al., 2005).

Currently, low-to-moderate severity mood disorders, somatic symptoms such as pain, fatigue, dizziness or intestinal discomfort, and important behavioral risk factors such as diet, exercise, sleep, substance use, and treatment adherence, are commonly addressed and treated in primary care. Generally only patients with severe or persistently unmanaged problems are referred for specialist care. As

2 Preface cognitive, behavioral, educational and supported self-management interventions are first-line treatments for most of these problems, health care models that incorporate these interventions into primary care practice or referral patterns are needed to ensure optimal accessibility and implementation of these treatments and, ultimately, maximize the cost-effective delivery of finite services.

KEY OBJECTIVES It is evident that mechanisms to decrease national health care costs are of vital and urgent importance. Cost-effectiveness is key to maximizing use of the most impactful interventions within limited resources. If behavioral health interventions show greater long-term benefits, this could justify higher costs up front since the overall savings would be greater.

In Volumes I-III of the Best Practices series published by the Institute for Brain Potential, we review the evidence base for the clinical effectiveness of behavioral health interventions for a range of neuropsychiatric and medical conditions. In this volume, we present a brief review of clinical effectiveness, but focus on the cost benefits of these behavioral health interventions.

Cost-effectiveness measures vary widely. Given the low number of trials to date, we have used broad criteria to provide as much data as possible about current behavioral health interventions, including from comparable developed nations. In some cases, costs and effects are provided separately. It may be valuable to consider the cost offsets of an intervention, specifically whether intervention costs are compensated for by cost-savings in later health care use.

Prior reviews of cost-effectiveness data for specific interventions typically refuse to draw overarching conclusions, given the low number of studies, immense heterogeneity, and poor quality of findings. What we have compiled here is only the starting point; the generalizability of many findings is untested and many questions remain unanswered.

KEY CONCEPTS For those seeking a deep understanding of cost-effectiveness methodology, many comprehensive and comprehensible resources already exist (e.g., Drummond et al., 2015; Gray & Clarke, 2011; Levin & McEwan, 2001). Below, we provide a high-level summary of the key concepts needed to understand and interpret the compiled findings presented in this book.

Clinical Effectiveness Ideally, interventions would be selected solely for their clinical effectiveness, or their ability to improve health-related outcomes (e.g., a decrease in depressive symptoms or a reduction in blood pressure). However, real-world health care decisions are constrained by limited resources, requiring a trade off of selecting between different treatment options within a fixed budget. Clinicians, patients, health care systems, and third-party insurers must all consider both clinical effectiveness and associated costs when recommending treatment options. This is particularly important when deciding between multiple treatment options.

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Cost-Effectiveness Cost-effectiveness creates a combined measure for both clinical effectiveness and associated costs by calculating the cost per unit of health outcome (i.e. incremental cost per incremental clinical improvement). For example, one intervention may cost $4 per one-point improvement on a depression scale, while another may cost $20 per one-point improvement on the same depression scale. By standardizing the cost per unit of health outcome, the two interventions can be directly compared. In this example, the first intervention is clearly more cost- effective than the second since it costs $16 less per each 1-point improvement.

These comparisons are only meaningful if the clinical outcomes and intervention costs are measured in the same way. For instance, outcomes could be measured using a 10-question depression scale in one study and a 100-question depression scale in another study. This means a one-point improvement is equivalent to a 10% improvement on the first scale but only a 1% improvement on the second one. Likewise, cost measurements could be limited to the direct implementation costs in one study and include the indirect costs of missing work in another study. Unfortunately, measurement variations like these are common, often making comparisons difficult and inappropriate altogether.

Cost-effectiveness analyses can also identify interventions that may have been ruled out previously. For example, interventions without significant clinical or cost differences separately may still be cost-effective overall. In other cases, even if an intervention is not cost-effective on its own it may still show cost offsets. In this case, costs spent on the intervention may offset future medical costs for the person being treated.

Quality-Adjusted Life Year (QALY) As mentioned earlier, using a standard metric for clinical outcomes makes comparisons more feasible. The most common standardized measure for cost- effectiveness is the quality-adjusted life year (QALY). The QALY measures the number of additional years of life gained by treatment, adjusting for the quality of those years. This adjustment accounts for the variability in the individual’s health status (e.g., bed-ridden to fully functional) during those additional years of life on a scale of zero (dead) to one (perfect health).

One limitation of the QALY is that it still requires a researcher to assign the value from zero to one, to decide how a disorder impacts a person’s quality of life. If this weight is not the same between studies, it can also impact comparisons. To avoid this problem, most researchers reference previous studies and assign similar values for a given illness.

Using QALYs facilitates comparison across different interventions and across different types of illnesses. For example, a behavioral intervention for anxiety might cost $20,000 per QALY while a pharmacological intervention for hypertension might cost $30,000 per QALY. If forced to select only one option, the treatment for anxiety may be recommended over the one for hypertension as it costs less while leading to the same overall improvement in quality of life and

4 Preface life expectancy. A more interesting example is interventions that tackle multiple outcomes. For instance, a stress management intervention might improve anxiety and hypertension outcomes. Since QALYs reflect the overall health of the person, they can capture the combined benefits of improving both anxiety and hypertension simultaneously. This becomes more relevant as efforts move toward greater integration of physical and mental health care.

Cost-effectiveness studies that use QALYs as the measure of clinical improvement are technically known as cost-utility analyses.

Payer Perspective Whose costs are measured also matters. One way to measure costs is from the payer perspective (PP). In other words, which costs are included in a study depend on who is paying. In the United States, most clinical trials take a third- party insurance or health care system payer perspective. This means the costs typically considered are the direct costs covered by the insurance. This may be limited to the specific treatment costs (e.g., therapist salary, medication prescription) or include other health care costs beyond the specific treatment (e.g., other doctor appointments). Sometimes it can also include other non-health care costs incurred by the patients and their families (e.g., transportation). Less commonly, the payer perspective can also be limited to the specific provider or to the patient.

Societal Perspective The gold standard is to conduct the analysis from the societal perspective and assess the change in all costs related to the disorder, beyond merely those that impact the health care payer or patient directly. For example, persons with substance use disorder may commit crimes as part of their drug-seeking behaviors. Costs accrued by the victims of these crimes and the criminal justice system would be included in an assessment of the impact of a substance use disorder treatment from a societal perspective, but not from a health care payer perspective. Likewise, persons with depression may have greater absenteeism and lower productivity at work. Depression-related costs accrued by an employer or a disability benefit provider would be included from a societal perspective, but not from a health care payer perspective. With behavioral interventions, a societal perspective can better capture the full effects that the intervention may have beyond the immediate health target at that time.

However, it is difficult to measure societal costs. Most studies do not include costs related to medical complications, other health consequences of the disorder, or the non-health adverse effects of the disorder on the patient, family, employers, government, and other members of society. Assessing the national economic impact of an intervention requires extensive measurement of outcomes across domains and over time. This is rarely feasible in a clinical trial. Societal costs include lost productivity (e.g., partial or complete absence from work), impaired social functioning, premature death, reduced occupational or educational attainment, as well as intangible costs related to experience of life (e.g., pain, suffering) and quality of life for other members of society. Understandably, assigning value to these societal costs is complex and may not

5 Preface be measured in the same way across different studies. Thus, comparison of studies is difficult not only because costs differ between health care systems and societies, but also because of the wide variety of perspectives taken and methodologies used in different studies.

Incremental Cost-Effectiveness Ratio (ICER) The most common cost-effectiveness measure is the incremental cost effectiveness ratio (ICER). The ICER measures the added cost per unit of health outcome (e.g., one-point improvement in depression score or QALY). To measure how much a treatment costs and how much it improves clinical outcomes, it needs to be compared to another treatment or control group. This helps account for the costs or improvements that might occur over time in the absence of the intervention.

To calculate the incremental cost-effectiveness ratio, take the difference between the cost of intervention and the cost of the control and divide by the difference between improvements in the intervention group and the control group:

Costintervention – Costcontrol ______

Improvementintervention – Improvementcontrol

This measures the additional costs of the intervention in terms of additional improvements produced by the intervention (e.g. $ per QALY gained). For example, consider a trial comparing a course of psychotherapy plus medication versus medication alone in terms of QALY after 12 months. The ICER would be calculated as the difference in costs per patient for those receiving psychotherapy and medication versus those receiving medication alone divided by the difference in QALY scores between those receiving psychotherapy and medication versus those receiving medication alone. This would provide an ICER indicating the additional cost per additional QALY gained by adding psychotherapy to the medication compared to the medication alone. So, if psychotherapy plus medication cost $2000 per patient and caused a improvement of 2 QALY after 12 months, and medication alone cost $1000 per patient and caused an improvement of 1 QALY after 12 months, then the ICER would be $2000-$1000=$1000 divided by 2 QALY - 1 QALY=1 QALY, or $1000/QALY. This ICER indicates that it would cost $1000 to gain each additional QALY by adding psychotherapy to medication in this example.

Incremental Net Benefit (INB) Cost-benefit analysis is another standardized comparison, but it does not rely on the QALY. Instead, a monetary value is assigned to the incremental clinical improvement (e.g., a one-point improvement in a depression scale is worth $10 or a one-QALY improvement is worth $50,000). This means both the costs and benefits are measured in terms of money. Thus, the incremental net benefit (INB) is the difference between the actual cost of intervention and the assigned cost of the benefit. For example, an intervention may cost $40,000 but lead to a one-QALY improvement worth $50,000, so that overall incremental net benefit is $10,000. A positive INB indicates the clinical benefit exceeds the costs, while a negative INB indicates the costs exceed the clinical benefits.

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Willingness to Pay Threshold As must be evident by now, cost-effectiveness is not the same as cost-saving. Improving health costs money, but cost-effectiveness helps decide what might be a reasonable amount to pay for that improvement. Incremental cost-effectiveness ratios make it easier to compare two options, as in the earlier examples where it cost $4 or $20 per one-point improvement in a depression measure or where it cost $20,000 or $30,000 per QALY for an anxiety intervention compared to a hypertension one. However, even after selecting the more cost-effective of the two options, the decision-maker would still need to decide whether $4 per one- point improvement or $20,000 per QALY are reasonable amounts to pay for the value being gained.

The willingness to pay threshold provides a ceiling value on a reasonable cost to generate the associated improvement (e.g., $10 for a one-point improvement on a depression scale). Ideally, standard thresholds would be established to facilitate comparison across trials and improve decision-making within large health care systems. This would also be vital for maintaining rigorous ethical standards when assigning monetary value to people’s health. However, willingness to pay thresholds can vary immensely depending on the clinical measures used. A payer might be willing to pay only $10 per one-point improvement on a depression scale but $5,000 per one-year abstinence for a person with substance use disorder or $50,000 per QALY.

The QALY again allows for meaningful comparisons. The most commonly used benchmark in the United States is $50,000 per QALY (Gold et al., 1996; Ubel et al., 2003; Braithwaite et al., 2008; Weinstein 2008). In the United Kingdom, the official guidelines suggest £20,000 to £30,000 per QALY. On an international level, the World Health Organization (WHO) recommends the maximum cost per QALY should be three times the gross domestic product (GDP) per capita. Unfortunately, most other clinical measures do not have established ceilings yet.

Cost-Effectiveness Acceptability Curves (CEAC) A cost-effectiveness acceptability curve (CEAC) uses observed data to estimate the probability that an intervention is cost-effective compared with the alternative across a range of possible willingness to pay thresholds. An ICER is an estimate that can have a small or large amount of variation. The findings generated by these curves help compensate for this variation by providing the probability of cost-effectiveness at different thresholds. For example, while the point estimate of an ICER (e.g., $20,000 per QALY) may appear to be within a willingness to pay threshold, it may have a wide range (e.g., 95% confidence interval from $2,000 to $70,000). Thus, the probability the intervention is cost-effective must be estimated based on the willingness to pay threshold. For instance, if an intervention may have 50% probability of being cost-effective if the willingness to pay threshold is $20,000 per QALY, and a 64% probability of being cost- effective if the threshold is $30,000 per QALY.

Clinical Effectiveness Versus Cost-Effectiveness Clinical effectiveness or cost-effectiveness may take priority depending on the

7 Preface decision being made. For example, a wealthy individual may be willing to pay whatever it takes and only care about clinical effectiveness in making treatment decisions regarding care for a loved one. Alternatively, a public health organization seeking to produce the largest population benefit out of a limited budget might instead look only at cost-effectiveness to choose the interventions likely to generate the greatest overall benefit for health across the population. In this text, we compiled data based on current practices and recommendations. Ultimately, each decision-maker will need to decide on their own willingness to pay thresholds.

Notably, the most cost-effective interventions are not always the most clinically effective. For example, an Internet-based therapy program may be provided at minimal cost but it may also only produce a modest improvement in symptoms. Although the intervention may not produce large clinical gains, the incremental gains per incremental cost may still be large if the costs are very low (e.g., one point of clinical improvement for $1). While an in-person therapy program may produce more robust clinical improvements, the greater improvements may cost much more to generate (e.g., four points of clinical improvement for $100). In this example, although the in-person treatment produces four times the clinical effect of the Internet-based treatment, the Internet-based treatment produces a unit of improvement at 25 times less cost. Thus, while the in-person treatment is more clinically effective, the Internet-based treatment is more cost-effective.

Interpreting Cost-Effectiveness The easiest decision occurs when an intervention is both more clinically effective and less expensive than the alternative option (i.e. the intervention is dominant). Similarly, it is an easy decision to not select an intervention when it is both less clinically effective and more expensive than the alternative option (i.e. the intervention is dominated). Dominant interventions will always be chosen over dominated ones. However, difficulties arise for the other two scenarios: when interventions are either more costly but more clinically effective, or less costly but also less clinically effective. In these cases, the willingness to pay threshold will help determine the appropriate choice between the intervention options. These clinical and cost comparisons can be represented as four quadrants:

Costs

↑ Costs Dominated ↑ Effects

Effects

↓ Costs Dominant ↓ Effects

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INCLUSION CRITERIA FOR RESEARCH REVIEWED IN THIS TEXT This review included randomized controlled trials (RCTs) with cost-effectiveness outcomes or some estimates of intervention-related costs. The core components of RCTs are the comparison of the intervention group to a control group not receiving the intervention, and random assignment of participants into the different groups. The associated costs may be measured directly during the implementation of the study or approximated using established cost systems (e.g., Medicare) to provide more representative data.

The majority of studies reviewed were identified via a 2014 PubMed search limited to randomized controlled trials and using the search terms “cost- effectiveness” and “psychotherapy” to identify cost-effectiveness related data for behavioral interventions for the prevention, treatment, and management of neuropsychiatric and medical chronic conditions. Additional studies identified through references or other sources that meet our inclusion criteria have also been reviewed. A few studies found to be of less robust methodology (e.g., pilot studies, small sample sizes) have been excluded. While we focused on behavioral interventions, we also included relevant studies of interventions to improve care delivery or comparisons to medical interventions (e.g., psychotherapy versus pharmacotherapy), as that data will also be of value to decision-makers.

Given the limited number of cost-effectiveness studies currently available and different metrics utilized to assess both costs and cost-effectiveness, it is almost impossible to compare across all trials in a reliable way. In most cases, we cannot extrapolate findings beyond what has been tested in trials; we are only able to present the available data. When possible, we draw conclusions from across existing trials to provide key recommendations.

CHAPTER FORMAT The book is subdivided into two main sections, one focused on neuropsychiatric disorders, that is mental health-related disorders, and one focused on behavioral medicine for other medical conditions. We include a final epilogue on health care delivery systems with promise for improving cost-effectiveness across conditions (e.g., collaborative care, Internet-based treatments, brief therapies). In the two main sections, each chapter focuses on a specific behavior or disorder and includes the following format:

• Background on Disorder: For each health target, we include the current prevalence (i.e. percentage of the population with the disorder) in the United States and current diagnostic guidelines. For neuropsychiatric disorders, we use the recently released fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); however, most studies reviewed use diagnostic criteria from the DSM-3 or DSM-4. In such cases, we report the authors’ original diagnostic classifications. In cases where diagnostic criteria have changed, we report the authors’ original diagnostic classifications.

• Prevalence of Disorder: The frequency with which a disorder occurs in a

9 Preface

population is relevant not only to its importance for clinical treatment but also to its contribution to the overall societal costs of the disorder. We include the most recent estimates available for the prevalence of each disorder in the United States. If data are unavailable, we attempt to provide estimates from comparable industrialized nations.

• Economic Burden of Disorder: Disease takes a significant economic toll on any nation, incurring significant direct (e.g., treatment) and indirect (e.g., lost productivity) costs for both the health care system and society at large. We include the most recent estimates available for the total annual costs of each disorder in the United States. If data are unavailable, we attempt to provide estimates from comparable developed nations.

• Clinically Effective Interventions: We provide a brief overview of current guideline-recommended interventions for each disorder, with a focus on psychosocial interventions that are included in available cost-effectiveness analyses. This includes the basic structure of the intervention, delivery format, and rationale for the treatment. For a comprehensive review of trials of the long-term clinical effectiveness of behavioral interventions, please refer to Best Practices in the Behavioral Management of Chronic Disease, Volumes I-III.

• Cost-Effectiveness of Interventions: We provide a comprehensive review of all currently available cost-effectiveness trials using the inclusion criteria enumerated earlier. When enough data are available, we organize the findings into categories both by specific demographic (e.g., age, sub-types, comorbidities) and type of intervention (e.g., psychotherapy, collaborative care, telehealth). In some cases, the limited number of existing trials precludes this organization. We also provide summary tables of all included trials, with the following columns:

o Study: Study reference (authors and year) and a brief description of trial. In cases where clinical and cost outcomes were reported in separately, we have included both references.

o Participants: Total number of participants who completed the cost- effectiveness trial, age range, diagnostic criteria, country, other relevant factors (e.g., gender, ethnicity), and number of participants per condition.

o Method and Intervention: Brief description of all study conditions, separated into Interventions (I) and Controls (C). In cases where no Control condition was included, the section is left blank. If more than one Intervention or Control condition was included, each option is numbered (e.g., I1, I2, C1, C2). Measurement time point is also included. Cost- effectiveness outcomes indicate the cost for producing the clinical improvement at that specific time point; the findings may be different at other time points, depending, for example, on the stability of the clinical gain and the additional cost of the intervention over time. For studies with measurements at multiple time points, only the last time point is included

10 Preface

unless there are notable reasons to include data from other time points.

o Clinical Outcomes: Clinical findings measure the intervention’s efficacy on the primary outcome measures. When possible, we calculate effect size in terms of Cohen’s d (abbreviated in the tables as “d”) to indicate the strength of the findings and to allow for better comparison across studies. Effect size is a standard measure of the size of the clinical effect compared to a control condition in units of standard deviation (SD). It is typically calculated as the difference between the means for clinical outcome in the intervention and control condition divided by the average of the standard deviations of the outcomes for the intervention and control condition:

Mean Outcomeintervention – Mean Outcomecontrol ______

[SDintervention + SDcontrol]/2

• Effect sizes of less than 0.4 are generally considered small effects, those from 0.4 to 0.8 are considered medium effects, and those of greater than 0.8 are considered large effects. It is important to note that effect size values only describe the strength of the effect, not the clinical significance. A small effect on a key clinical outcome may be more important than a larger effect on a less important clinical outcome. When effect size cannot be calculated from the published data, d is labeled non-calculable (NC).

o Cost-Effectiveness: Here we present the payer’s perspective (PP), incremental cost-effectiveness ratio (ICER) in terms of QALYs or other variables, incremental net benefit (INB), or just the associated total costs, depending on availability. For ICER, we use the terms dominant and dominated when appropriate. A negative ICER indicates the intervention was cost-saving (i.e. the intervention costs less than it saves). When possible, we include the assigned willingness to pay threshold(s) and the associated probability the intervention will be cost-effective at different thresholds. Values are bolded when they are within typical willingness to pay thresholds. This is only applicable to cases with established thresholds, which is primarily for QALYs.

• Limitations and Future Directions: In almost all cases, the biggest limitation is the paucity of cost-effectiveness trials. When possible, we suggest potential studies to address gaps in the literature. We consider factors unique to the given disorder; however, similar themes emerge across chapters.

• Key Points: We provide a review of the main takeaways from each of the sections. Given the current limitations in data and variation in methodologies, we are unable to provide a rank-ordered list from the most to least cost- effective intervention options for any given disorder. However, we highlight the broad conclusions both to summarize the current findings and inform the decision-making process to the best extent possible with the available data. It may be helpful to review the key points before reviewing the tables that describe the underlying trials.

11 Preface

RECOMMENDATIONS FOR THE GENERAL READER The chapter structure, as outlined above, was designed to provide an engaged reader with a concise overview of the disorder being considered, including symptoms, economic burden of disease, and clinically effective treatments, before providing an in depth review of all relevant cost-effectiveness trials available to date. We understand, however, that many health care managers and decision-makers may not have time or interest to attend to the entirety and details of cost-effectiveness trials in a domain, nor sufficient understanding of clinical trials design and interpretation to understand the nuances of findings displayed in the tables. Below we provide tips for getting the most out of this book with limited time or incoming knowledge of health economics.

A Bottom Line Up Front Approach: The literature on cost-effectiveness of behavioral health interventions is still in its infancy and there are many gaps in available knowledge. Given these gaps, findings may or may not be available to guide specific decisions. Thus, to get a sense of whether there is data to suggest a change in clinical practice or health care delivery system in a domain, we recommend first reading the Abstract and then skipping to the Key Points. These will provide an overview of the topic and the literature, and then a summary of conclusions from all included trials. If a health care decision-maker finds that the Abstract and Key Points do not suggest any changes in their current practices, then they may not need to read further.

Digging Deeper: If one finds that the Key Points suggest consideration of a different practice, then it is important to review the studies more closely to understand the details, strengths and limitations of the findings. Here, the next step is to read the text in the Cost-Effectiveness of Interventions section. In this text, we describe each of the studies and point out key details of the study population, intervention and comparison condition, and/or analysis or study design that limit or strengthen the main conclusions of the trial. For example, a trial might conclude that medication is more cost-effective than psychotherapy, but might have only looked at outcomes in the first 12 weeks after treatment initiation. Because psychotherapy may have long-term beneficial effects on health behaviors while medication may only be effective while it is taken, this conclusion may not hold at later times beyond those examined in the trial. Thus, this limitation might change clinical decision-making based on the trial. While at first pass medication might seem to be the superior option, lack of long-term data on cost-effectiveness might encourage a more balanced approach in real-world clinical practice; health care decision-makers might decide to either offer patients a choice of medication versus psychotherapy, or offer medication with psychotherapy for those with no or incomplete treatment response, rather than solely offering medication per the short-term cost-effectiveness outcomes. These sorts of key limitations are described in the text, and should help the reader make more informed and nuanced interpretation of the trials, and avoid over- reaction to what are often very preliminary or incomplete conclusions.

If these trials still suggest a change, expansion, or elimination of a clinical practice, it is often important to understand the findings in depth, including the

12 Preface expected clinical and cost impact of a specific intervention. Here, the tables are designed to provide you with an overview of all of the key elements of the trial including specific outcomes. To keep the tables concise, we provide a large amount of data in a tight structure. Once you learn to unpack it, you can pull the core elements of each trial from the table at a glance. To aid in this process, we provide several examples to walk you through interpretation. We provide a glossary of common abbreviations used in the tables at the end of this chapter.

We begin with a walk-through of the first table in Chapter 1:

Table 1. Behavioral Interventions for Anxiety Disorders in Children and Adolescents Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Bodden et al. 116 children Interventions: Percent PP: Societal (2008) (age 8-17 (1) Family Anxiety-Free years) with Cognitive Children ICER (per Family or anxiety Behavioral (AFC): QALY): individual disorders in Therapy I1: 53% €200514,950 Cognitive the (CBT) for 12 I2: 68% Behavioral Netherlands. sessions. (NS) Willingness to Therapy for 57 in (2) Individual pay threshold: clinically intervention Cognitive If value is anxious #1, 59 in Behavioral €2,500/QALY, children intervention Therapy 36% #2. (CBT) for 12 probability sessions. family CBT is more cost- Measures: effective than 1-year follow- individual up CBT. If value is €37,500, 19% probability more cost- effective.

ICER (per AFC):

€20051,993.33

The point estimates of both ICERs indicate dominance of individual over family CBT.

13 Preface

As described in the Table title, this table summarizes the randomized cost- effectiveness trials of behavioral interventions for anxiety disorders in children and adolescents. The single entry in the table means there has only been one trial to date. The “Study” column lists the first author and year of the study, so that you can quickly find the full reference in the references section at the end of the chapter if you want to read the full article. We then provide a quick summary of the interventions tested in the trial. In this case, the trial compared cognitive behavioral therapy delivered in sessions with the whole family versus in sessions with individual anxious children alone. This allows you to quickly scan for trials that address specific interventions in which you are interested.

The “Participants” column provides a brief description of the number and types of patients included in the study. There are a few key things to pay attention to in this section. First, consider the description of the study participants; in this case, children age 8 to 17 with anxiety disorders. Is this population comparable to the population you are interested in? For example, if you were interested in developing a treatment program for preschool children with anxiety, then these findings among older children may not be relevant. Next, this section provides information about the setting of the study; in this case, the Netherlands. Here, you must consider whether there are differences between your setting and the study setting that might affect your ability to translate the work. In this case, different types of cognitive behavioral therapy are likely to be consistent across countries and health care systems, and so this is probably not a big factor in interpreting outcomes. In many cases, however, the control condition is “treatment as usual.” Treatment as usual may differ substantially from health care system to health care system, from one country to another or over time. Lastly, look at the number of participants included in the trial. Trials with low numbers of participants often find no difference between conditions simply because they did not include enough people to detect differences. Trials with low numbers of people can also be impacted disproportionately by one or two strange occurrences (e.g., a participant who gets in a car accident and incurs unexpected and likely unrelated medical costs and health problems). Generally, you should be more confident drawing conclusions from trials with large numbers of participants than those with low numbers of participants.

The “Method and Intervention” column provides a very brief description of the intervention(s) and the comparison condition. Here, it is extremely important to understand to what the intervention is being compared. The cost-effectiveness findings will typically be expressed in terms of the cost per benefit gained, where benefit ‘gained’ is in comparison to something else. This is key to understanding findings, as often decision-makers will frame their question as “what is the cost- effectiveness of an intervention?” An absolute answer to this is almost never available, as it is rarely ethically or logistically possible to have a control condition that offers no treatment at all. In other words, you will usually have trials that compare the cost-effectiveness of one intervention to another existing treatment option. If the comparison option is not similar to options in your health care system, it can be challenging to apply the findings to your setting. Understanding the intervention and its control condition can help with

14 Preface translation. If a control condition is already a clinically effective intervention, then the added benefit of the new intervention being tested is likely to be relatively small. In this section, it is also useful to consider the time frame of the study in relationship to the timing of the expected costs and benefits of the intervention. In this example, the costs and outcomes were measured in the first year after starting treatment. Is this long enough? If measurement is too soon, you may incur all the costs of the intervention but not yet see the full benefits. If measurement is too late, then effects of the intervention may be washed out by later, unrelated events.

The reader is now ready to consider the clinical effectiveness of the intervention. The Clinical Outcomes column contains the main clinical effects observed in the trial. In this example, a majority of children in both groups were anxiety-free one year after the start of the study (53% in the family group, and 68% in the individual group). While that 15% difference looks like it could be meaningful, there was no statistical difference between groups, as designated by the “(NS)” for not significant. This tells us that there was no statistically reliable difference between the two treatments. In other words, if you are only considering clinical effectiveness then either treatment would be an acceptable choice. The clinical findings will often be followed by two statistics that summarize the size and statistical difference between the two groups, although neither are available for this example study. The symbol “d” indicates the effect size of the intervention compared to the control, specifically the difference in the outcome between the two groups in units of standard deviation. This gives you a sense of how big of a difference there was between the two groups, and since it is in standard units that it also allows you can to compare clinical effectiveness across trials. This can be helpful when comparing unfamiliar or different clinical outcomes (for example, number of anxiety-free days versus change in a standardized anxiety symptom assessment scales). Putting results in comparable units can help you compare effects across interventions and measures. In this example study, the needed data to calculate effect size was not reported. The P statistic tells you how likely it is that the two groups have the same effect, ranging from 0 for very unlikely they have the same effect to 1 for very likely they do have the same effect. Generally, a p-value of less than 0.05 is considered evidence that the two groups have statistically different outcomes for participants since it indicates a less than 5% chance that the groups have the same effect. A p-value more than 0.05 (e.g., 0.54, indicating a 54% chance that the outcomes for the groups are the same) is generally taken to mean that either the groups do not have different outcomes, or the trial was too small to observe reliable differences between groups. When p is greater than 0.05, the comparison may sometimes be reported simply as “not significant” or “NS” in the table.

The last column includes the main findings of interest. The Cost-Effectiveness column provides information about the comparative cost-effectiveness of the interventions; in this case, family versus individual cognitive behavioral therapy. At the top, we provide information about the Payer Perspective (PP) of this study. In other words, this indicates how costs were measured depending on who would be paying for the costs. Most frequently, studies are done from a “health care” perspective, considering the costs and savings of the intervention

15 Preface from the perspective of the health care provider or insurance company. In this case, the “PP: Societal” indicates that the study was done from a “societal” perspective, suggesting it included costs and benefits not only to the health care provider, but also to others, such as family, taxpayers, employers, and others. Next, we provide the main findings from the cost-effectiveness analysis. In this example, this is the Incremental Cost-Effectiveness Ratio (ICER), or the cost per each additional quality adjusted life year for doing family versus individual therapy. Here, the study estimated that it would cost about 15,000 euros for each additional quality adjusted life year gained or about 2,000 euros for every additional anxiety-free child by doing individual instead of family therapy. To judge whether that is an acceptable cost, you can compare to existing standards or to your own valuation of the outcome. For example, 15,000 euros is less than the recommended ceiling for a QALY per existing guidelines, suggesting the intervention is reasonably cost-effective. We then present a summary of findings from the study’s estimation of Cost-Effectiveness Acceptability Curves. This is listed under “Willingness to pay threshold.” Here it shows that at increasing valuation of quality adjusted life years, the family therapy treatment becomes progressively less likely to be cost-effective, and the individual therapy is always more likely to be cost-effective. Based on an overall finding that individual therapy fared better on clinical outcomes, and cost less, individual therapy was found to be the dominant intervention, providing better outcomes for less money. This conclusion is included in italics in the table.

Next, we walk through a somewhat more complicated trial, with 3 interventions plus a control condition tested (excerpt from Table 1, Chapter 2): Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Domino et al. 369 patients Interventions: Children’s PP: Societal (2008 & 2009) (age 12-18 (1) Selective Depression & March et al. years) with serotonin Rating Scale ICER (per (2004) depression reuptake (CADS): QALY):

across 13 sites inhibitor I1: 36.30 (8.18) (1) $200323,737 Treatment of in U.S. 57% (SSRI; I2: 42.06 (9.18) (2)

Adolescents female. fluoxetine) I3: 33.79 (8.24) $20039,210,622 with alone for 12 C: 41.77 (7.99) (3) $2003123,143

Depression 94 in inter- weeks. (4) $2003458,818 Study (TADS) vention #1, (2) Cognitive d1: .677 comparing Behavioral d2: -.034 Willingness to Cognitive 89 in inter- Therapy d3: .983 pay threshold: Behavioral vention #2, (CBT) alone d4 (I3 vs. I1): If value is Therapy, for 12 weeks. .306 $200K/QALY, selective 92 in inter- (3) SSRI plus both SSRI serotonin vention #3, CBT for 12 alone and reuptake weeks. SSRI plus CBT inhibitor, and 94 in control. are ≥95% both Control: probability combined Placebo for 12 more cost- weeks. effective than

16 Preface

placebo. Measures: 12 weeks

In the “Study” column, we see that the findings from this clinical trial, named TADS, were published in three manuscripts, with the authors and dates provided so these can be quickly identified in the references. This section also indicates that the clinical trial examined three interventions: a psychotherapy intervention, a medication, and both combined.

In the “Participants” column, we learn that the trial recruited children of mixed gender between the ages of 12 and 18 who had been diagnosed with depression. The trial was fairly large with 369 children included. This increases the likelihood that the trial can distinguish differences in outcomes and costs between the interventions. There were 13 separate trial sites included, which increases generalizability of the study findings. With the interventions provided at that many sites, it is less likely that differences between groups were due to special conditions at one site (e.g. an exceptionally good or bad psychotherapist delivering the therapy).

In the “Methods and Intervention” column, we learn more details about the interventions and control conditions. The first intervention was 12 weeks of medication; specifically, the drug fluoxetine. The second intervention was 12 weeks of cognitive behavioral therapy with no medication. The third intervention was 12 weeks of medication and cognitive behavioral therapy. All three interventions were compared to a placebo condition, where participants got an inactive pill. The “Measures” section indicates that clinical and cost outcomes were assessed at 12 weeks. This time point is reasonable for seeing the early effects of depression treatment, but may ignore longer-term benefits of this treatment, and longer-term costs associated with maintaining gains achieved with these treatments over time.

The “Clinical Outcomes” column summarizes the clinical benefits of the four interventions. The authors used a standardized depression assessment for children, the Children’s Depression Rating Scale (CADS), where lower scores indicate fewer depression symptoms. Participant’s average scores on these measures at 12 weeks are provided, along with the standard deviation within the group in parentheses, for participants within each intervention group. Participants who received the placebo scored about 42 on the CADS assessment at 12 weeks. Participants who got psychotherapy alone scored about the same. The participants who received the medication had somewhat lower CADS scores at about 36, while those who received both medication and psychotherapy scored even lower, at about 34. The effect size statistic (d) summarizes the size of these effects, which allows for comparisons to studies that use different measures. d1 through d3 show effect sizes in comparison to the placebo control. These show that the psychotherapy intervention (#2) had almost no effect, with a d close to zero. Medication (#1) had a medium-sized effect with d=.67. Medication plus psychotherapy had a large size effect with d=.98. d4 compares the two effective interventions, medication alone to medication plus

17 Preface psychotherapy and shows that adding psychotherapy to medication has a small additional benefit, with d=0.3. Altogether, these clinical findings suggest that costs being equal, medication plus psychotherapy is the best choice, with medication alone being the second best choice.

The “Cost-Effectiveness” column will help determine which treatment is the best value per unit of improvement. It first provides information about the Payer Perspective. In this case, the study took a societal perspective, including costs beyond the health care payer. The section labeled “ICER (per QALY)” indicates that cost-effectiveness data were calculated using the standard cost-effectiveness units in terms of quality adjusted life years. Because of the placebo condition, this trial provides relatively rare data on the cost-effectiveness of the interventions in comparison to no active treatment. In this section, we can see that the medication intervention produces an improvement of 1 QALY at a cost of $23,737 in 2003 dollars. This is within virtually all standard willingness to pay thresholds for considering an intervention cost-effective. Conversely, the psychotherapy intervention produces an improvement of 1 QALY at a cost of over $9.2 million dollars. This is well above virtually all standard willingness to pay ranges for considering an intervention cost-effective, suggesting this is not a cost-effective option. The ICER for medication plus psychotherapy is a bit harder to interpret at an improvement of 1 QALY at a cost of $123,143. This is at the high range of recommended standard willingness to pay ranges for a QALY. Here, decisions about whether the combined intervention is worth providing will really depend on how much an organization values the quality of life improvements gained. To help further with this decision-making, the study also provide an ICER comparing the medication alone intervention with the medication plus psychotherapy intervention. This result indicates that adding psychotherapy to the medication intervention adds to clinical benefit at the cost of over $450,000 per QALY. As $450,000 per QALY is well above recommended standard willingness to pay thresholds for QALYs, this suggest that based on cost- effectiveness findings, the medication alone intervention is the favored option. However, if one highly values clinical benefits, using a willingness to pay threshold of $200,000 per QALY, both the medication only and the medication plus psychotherapy have a 95% chance of producing the a gain of 1 QALY for under $200,000. This is described in the section under “Willingness to pay threshold”.

With experience, the reader will learn to quickly interpret data in the tables, making these a useful resource for understanding the key findings of a given clinical trial. We hope that the detailed review provided in this book will help guide improvements in behavioral health care delivery for health care systems across the globe.

18 Preface

Glossary of Common Abbreviations in the Tables QALY: Quality Adjusted Life Year, the gold standard measure for cost- effectiveness analyses, a measure that considers both improvement in quality of life and life years gained.

PP: Payer Perspective, the perspective from which costs are measured.

ICER: Incremental Cost-Effectiveness Ratio, the cost per unit benefit gained in receiving the intervention versus the control. For reporting of ICER, a negative sign before a currency value indicates currency saved. Positive currency values indicate currency spent.

INB: Incremental Net Benefit, the difference between the cost of the intervention and the monetary value assigned to the benefit gained. For reporting of INB, a positive sign indicates net savings.

NS: Not significant, indicating lack of statistical difference between groups.

NC: Not calculable, indicating that required data was not reported in the trial. d: Effect size, indicating the difference between the group means in units of standard deviation. This should not be confused with clinical importance of the effect.

P: P-value, indicates the probability that the two groups are indistinguishable.

I: Intervention, the treatment being tested.

C: Control, the comparison condition.

95% CI: 95% Confidence Interval, indicating the range of values between which the investigator is 95% confident that the true mean lies.

Common Currency Abbreviations: $: United States dollar AU$: Australian dollar CN$: Canadian dollar £: British pound €: Euro

The number in subscript after the currency symbol (e.g. 2000) indicates the year in which the costs were calculated. For older studies, costs may need to be adjusted for inflation before they can be compared to more recent findings.

19 Preface

REFERENCES

Altarum Institute. Insights from Monthly National Health Spending Data through December 2015. Center for Sustainable Health Spending. February 12, 2015.

Anderson, G. (2010). Chronic Care: Making the Case for Ongoing Care. Retrieved May 7, 2015, from http://www.rwjf.org/files/research/50968chronic.care.chartbook.pdf

Braithwaite RS, Meltzer DO, King JT Jr, Leslie D, Roberts MS. What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule? Med Care 2008;46 (4) 349- 356.

Centers for Medicare and Medicaid Services. National Health Expenditures 2013 Highlights. Retrieved May 7, 2015, from http://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends- and-Reports/NationalHealthExpendData/downloads/highlights.pdf

Claxton G, Kamal R, Cox C. (2014). How health spending patterns vary by demographics in the U.S. Peterson-Kaiser Health System Tracker. Kaiser Family Foundation. Published December 17, 2014. Retrieved May 21, 2015, from http://www.healthsystemtracker.org/2014/12/how-health-spending-patterns- vary-by-demographics-in-the-u-s/

Drummond MF, Sculpher MJ, Claxton K, Stoddart GL, Torrance GW. Methods for the Economic Evaluation of Health Care Programmes. 4th Edition. New York, NY. Oxford Medical Publications : 2015.

Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-Effectiveness in Health and Medicine. New York, NY. Oxford Press University: 1996.

Gray AM, Clarke PM, Wolstenholme JL, Wordsworth S. Applied Methods of Cost-effectiveness Analysis in Health Care. New York, NY. Oxford University Press: 2011.

Kessler RC, Heeringa S, Lakoma MD, Petukhova M, Rupp AE, Schoenbaum M, Wang PS, Zaslavsky AM. Individual and societal effects of mental disorders on earnings in the United States: results from the national comorbidity survey replication. Am J Psychiatry. 2008 Jun;165(6):703-11.

Levin HM, McEwan PJ. Cost Effectiveness Analyses: Methods and Applications, second edition. Thousand Oaks, CA. Sage Publications: 2001.

Peterson-Kaiser Health System Tracker. Contributions to Total Health Care Expenditures by Individuals, 2012. Retrieved on July 17, 2016, from: http://www.healthsystemtracker.org/chart-collection/how-do-health- expenditures-vary-across-the-population/?slide=1.

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Lehnert T, Heider D, Leicht H, Heinrich S, Corrieri S, Luppa M, Riedel-Heller S, König HH. Review: health care utilization and costs of elderly persons with multiple chronic conditions. Med Care Res Rev. 2011 Aug;68(4):387-420.

Stanton MW, Rutherford MK. The high concentration of U.S. health care expenditures. Rockville (MD): Agency for Health care Research and Quality; 2005. Research in Action Issue 19. AHRQ Pub. No. 06-0060.

Ubel PA, Hirth RA, Chernew ME, Fendrick AM. What is the price of life and why doesn't it increase at the rate of inflation? Arch Intern Med 2003;163 (14) 1637- 1641.

Weinstein MC. How much are Americans willing to pay for a quality-adjusted life year? Med Care 2008; 46 (4) 343- 345.

21 Anxiety Disorders

CHAPTER 1: ANXIETY DISORDERS

ABSTRACT Anxiety disorders are the most common class of neuropsychiatric disorders. These include Generalized Anxiety Disorder (GAD), Panic Disorder (PD), Obsessive-Compulsive Disorder (OCD), Post-Traumatic Stress Disorder (PTSD), Social Anxiety Disorder (SAD), and Specific Phobia. It is estimated that 28.8% of the U.S. population will experience an anxiety disorder during their lifetime, with national direct and indirect costs totaling $42.3-$46.6 billion annually. These costs are likely underestimates due to the early age of onset, high chronicity, and frequent multimorbidity of anxiety disorders.

Most cost-effectiveness analyses of behavioral interventions for anxiety disorders include Cognitive Behavioral Therapy (CBT)-based treatments. In children and adolescents, individual CBT appeared to dominate family CBT but lacked comparisons to medication or usual care. For PD, in-person CBT alone or combined with antidepressants was more cost-effective than antidepressants alone or usual care. However, antidepressants alone could be more cost-effective for short-term benefits. Cost-effectiveness between CBT alone and CBT combined with antidepressants varied depending on the willingness to pay threshold. Different delivery formats of CBT (e.g., brief, group, Internet-based) were more cost-effective than standard CBT. Group CBT also had the potential to be cost- effective for preventing PD in those with subclinical symptoms.

For OCD, Exposure and Response Prevention (ERP) was more cost-effective in stepped care or computer-guided formats—the latter only for lower willingness to pay thresholds—than in its standard format, but was not compared to medication or other treatments. For PTSD, Prolonged Exposure Therapy (PE) dominated antidepressants and treatment choice dominated no treatment choice. For SAD, cost-effectiveness of CBT or Psychodynamic Therapy (PDT) depended on the willingness to pay threshold, but Internet-based CBT was cost-saving over group CBT up to four years later. For Health Anxiety, standard, brief, and Internet-based CBT all appear promising as cost-effective or cost-saving. For anxious patients in emergency departments, a stepped care program was cost- saving, but cost-effectiveness of brief CBT or medication depended on the willingness to pay threshold.

For co-occurring medical conditions, cost-effectiveness varied widely depending on the specific condition (e.g., asthma, cancer). In general, non-standard care delivery systems were more cost-effective than standard individualized, in- person care. Both Internet-based CBT (with and without minimal therapist support) and regular or stepped Collaborative Care Management in primary care (often including CBT and/or medication) were cost-effective across multiple anxiety disorders. Further, Internet-delivered CBT was cost-effective for older adults. Stepped care programs for preventing onset of depressive and anxiety disorders in high-risk older adults had conflicting findings. Overall, evidence supports cost-effective CBT-based solutions—especially non-standard delivery systems (e.g., group, telehealth, collaborative, stepped) in primary care—for

22 Anxiety Disorders

most types of anxiety disorders, but further research is warranted for prevention and in specific populations (e.g., children, older adults, medical conditions).

BACKGROUND Anxiety disorders consist of magnified or extended versions of otherwise normal responses to stressful or fear-inducing occurrences, which negatively impact life functioning. Common symptoms including overwhelming feelings of panic and fear; painful, intrusive memories; recurring nightmares; uncontrollable, obsessive thoughts; and physical symptoms such as startling easily, tense muscles, pounding heart, and feeling sick in the stomach.

Additionally, each subtype has its own unique symptoms, behavioral patterns, and treatment recommendations:

• Generalized Anxiety Disorder (GAD) is characterized by uncontrollable anxiety and excessive worry about multiple things for at least six months. Physical symptoms include fatigue, sleeping difficulties, irritability, impaired concentration, and muscle tension, typically interfering with life and work. To date, no cost-effectiveness trials are limited exclusively to GAD.

• Panic Disorder (PD) is characterized by recurrent and unexpected panic attacks, as well as chronic fear about having another attack. Physical symptoms include racing heart, trembling or shaking, shortness of breath, and sweating. People with panic disorder often change their behavior substantially because of the attacks. In some cases, they may shut themselves away at home and avoid going out in public (i.e. Agoraphobia). Studies based on former diagnostic criteria often specify PD with or without Agoraphobia.

• Obsessive-Compulsive Disorder (OCD) is characterized by recurrent anxiety- provoking thoughts, images, or impulses (obsessions) or repetitive behaviors or thoughts to prevent anxiety or distress (compulsions) that interfere with functioning. Common obsessions include thoughts that something might be contaminated (e.g., by disease) or not completed (e.g., door not locked). Common compulsions include washing, checking, praying, or counting.

• Post-Traumatic Stress Disorder (PTSD) is characterized by a prolonged period of severe anxiety following a terrifying experience. Symptoms may include nightmares, flashbacks, and recurrent, unwanted memories of the experience. People with PTSD often avoid reminders of the experience, and remain on guard in fear of additional threats.

• Social Anxiety Disorder (SAD; formerly Social Phobia) is characterized by persistent fear of social situations in which persons worry about embarrassing or humiliating themselves. Persons may experience anxiety symptoms and/or avoid social situations.

• Specific Phobia is characterized by extreme or persistent fear of specific objects or situations (e.g., fear of falling), causing significant distress or

23 Anxiety Disorders

interfering with life. Persons go out of their way to avoid these fears or endure them with extreme dread.

The most recent version of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) no longer classifies Obsessive-Compulsive and Related Disorders (e.g., OCD) and Trauma- and Stressor-Related Disorders (e.g., PTSD) under Anxiety Disorders. However, all current data are based on earlier diagnostic criteria of DSM-3 or DSM-4, and we continue to include these disorders together. Due to a lack of available studies utilizing the new DSM-5 categorizations, Separation Anxiety Disorder, Selective Mutism, Agoraphobia, or Panic Attack are not included at this time.

Of particular relevance for medical populations is Health Anxiety or Hypochondriasis, which is characterized by excessive worry about one’s health to the point that it negatively impacts life functioning. This diagnosis technically falls under Somatic Symptom and Related Disorders since it can include unexplained somatic symptoms, although it can also occur without them. This distinction around somatic symptoms has been added to the new DSM-5, with Health Anxiety replaced by two separate disorders: Somatic Symptom Disorder (high health anxiety with somatic symptoms) and Illness Anxiety Disorder (high health anxiety without somatic symptoms). As before, the studies reviewed here use diagnostic criteria of DSM-3 or DSM-4 and we continue to refer to these disorders as Health Anxiety or Hypochondriasis. Crucially, this Health Anxiety may drive healthcare utilization and thus healthcare costs, as the person seeks excessive reassurance about concerns, symptoms, or fears.

PREVALENCE OF DISORDER Anxiety disorders have the highest lifetime prevalence of any neuropsychiatric disorder at more than a fourth (28.8%) of the U.S. population (CDC, 2013; Kessler, 2005). In the United States, approximately 40 million adults (18.1%) suffer from an anxiety disorder every year, of which 9 million adults (4.1%) are classified as severe (NIMH, 2014). Within the different disorder subtypes, the lifetime prevalence are as follow: Generalized Anxiety Disorder (6.2%), Specific Phobia (4.9%), Agoraphobia (3.1%), Social Anxiety Disorder (2.5%), Post- Traumatic Stress Disorder (2.1%), and Panic Disorder (1.2%; Somers et al., 2006).

Both the prevalence of anxiety disorders and their co-occurrence with other neuropsychiatric disorders are higher in women than men. In fact, women are 60% more likely than men to experience an anxiety disorder in their lifetime (McLean et al., 2011; NIMH, 2014). Compared to other neuropsychiatric disorders, it is possible that anxiety disorders have higher rates of co-occurrence with other disorders, with up to 50% of persons with an anxiety disorder having two or more anxiety disorders and up to 80% of those persons also having a depressive disorder (Kessler & Greenberg 2002; Katon et al., 2007).

Anxiety disorders are also correlated with higher prevalence for several broad categories of medical conditions, including cancer, diabetes, hypertension, cardiovascular disease, acute myocardial infarction, asthma, irritable bowel syndrome, dermatitis, and chronic pain (Roy-Byrne et al., 2008; Marciniak et al.,

24 Anxiety Disorders

2005). Significantly, persons with anxiety and/or depressive disorders experience more severe somatic symptoms from medical disorders than persons with the medical disorder alone (Katon et al., 2007).

ECONOMIC BURDEN OF DISORDER In the United States, anxiety disorders were estimated to cost approximately $42.3 to $46.6 billion in both direct costs (e.g., medical) and indirect costs (e.g., productivity losses) annually as of 1990, an increase of 38.3% from 1985 (Greenberg et al., 1999; DuPont et al., 1996). By one estimate, indirect costs were only 10% of total costs (Greenberg et al., 1999). But by another, they were more than 75% of total costs (DuPont et al., 1996). Moreover, neither of these account for additional indirect costs that may be incurred due to the adverse effects of relatively early onset of anxiety disorders (median age 15 years) compared to other chronic medical conditions or the highly increased risk for co-occurring disorders. Thus, it is believed that the costs of anxiety and stress disorders have routinely been underestimated (Kessler & Greenberg, 2002; Kessler et al., 2010).

Current data are inconsistent regarding the relative cost differences between the disorder subtypes. A retroactive database analysis limited to healthcare costs found Post-Traumatic Stress Disorder (PTSD) to be the most expensive anxiety disorder (Marciniak et al., 2005). Another review of cost-of-illness and cost- effectiveness studies concluded that Panic Disorder was the most expensive, and Generalized Anxiety Disorder (GAD) the least expensive in terms of total societal costs (Konnopka et al., 2009). Meanwhile, a review of 90 pharmacological studies focused exclusively on GAD across the United States, Europe, and Australia asserted GAD had a higher mean annual medical cost compared to other anxiety disorders (Revicki et al., 2012). Thus, it is not possible to conclude the relative economic burden of the different anxiety disorder subtypes at this time.

CLINICALLY EFFECTIVE INTERVENTIONS Since both pharmacotherapy and psychotherapy have demonstrated efficacy for anxiety disorders, selecting between the two is usually based on availability and patient preference. However, optimal treatment can also vary depending on specific clinical factors such as co-occurrence with other neuropsychiatric or medical disorders. First-line medication treatment includes selective serotonin reuptake inhibitors (SSRIs) for all disorders, serotonin-norepinephrine reuptake inhibitors (SNRIs) for some disorders, and pregablin for Generalized Anxiety Disorder. It is also recommended that all patients should receive supportive therapy. For behavioral treatment, Cognitive Therapy, Cognitive Behavioral Therapy, and Exposure Therapy are clinically effective (Baldwin et al., 2005). Finally, combined pharmacological and psychotherapeutic treatment may be recommended as the most effective option for some disorder subtypes (Bandelow et al., 2012).

Cognitive Behavioral Therapy (CBT) is designed to identify and target maladaptive thoughts and behaviors. For anxiety disorders, this includes learning how to transform thinking patterns that support fears and how to modify reactions to anxiety-provoking situations. Cognitive Therapies are similar but focus more on changing maladaptive thoughts than behavioral skills

25 Anxiety Disorders

training. Exposure Therapy is a specific form of CBT that involves gradual exposure to the feared situation or object in a controlled environment. It is effective for Agoraphobia, Obsessive-Compulsive Disorder, Post-Traumatic Stress Disorder, Social Anxiety Disorder and Specific Phobia (Bandelow et al., 2012; Powers et al., 2010). A specific version, Exposure Response Prevention (ERP), is commonly used to treat Obsessive-Compulsive Disorder. In addition to gradual exposure, the patient must inhibit their compulsive behaviors in response to cues. Another specific version, Prolonged Exposure Therapy (PE), is highly effective for Post-Traumatic Stress Disorder. It incorporates patient education, retraining breathing, exposure practice with real-world situations, and talking through the trauma.

The delivery of these CBT-based treatments can also be adapted for different needs. A therapy may include family members, be presented in a group format, be provided by peers as self-therapy, or be administered via a computer. Additionally, Collaborative Care Management is an effective care delivery model to improve clinical outcomes. This model provides additional support by utilizing case managers. They can help manage and monitor care and treatment progress. They may serve as a liaison with primary care doctors and any mental health providers. This role may include patient education, support for treatment adherence, and promotion of self-care to improve clinical care and health outcomes.

COST-EFFECTIVENESS OF INTERVENTIONS Cost-effectiveness of anxiety interventions is measured using multiple outcomes including QALYs, number of anxiety-free days (AFDs), number of improved or recovered patients, and incremental improvements on specific anxiety measures (e.g., Panic Disorder Severity Scale). Other than the standard cost-effectiveness metric of $50,000 per QALY, no willingness to pay thresholds have been established to compare treatment options for anxiety disorders.

A prior review of all randomized controlled trial (RCT)- and modeling-based cost-effectiveness studies of anxiety disorders through 2008 found significant methodological differences. This not only limited comparability across trials but also led to significant variation in cost estimates. The reviewers observed an emphasis on Panic Disorder and Generalized Anxiety Disorder due to their perceived higher medical costs, with a corresponding lack of studies on Agoraphobia, Social Anxiety Disorder, and Specific Phobia. In fact, the higher prevalence of these latter disorders could lead to higher societal costs. Overall, while both pharmacotherapy and psychotherapy have demonstrated clinical efficacy for anxiety disorders, no conclusive evidence exists for advantages of one over the other. However, some research indicates CBT may be more cost- effective than medication (Konnopka et al., 2009).

Anxiety Disorders in Children and Adolescents To date, only one RCT has investigated cost-effectiveness of behavioral interventions for anxiety disorders in children and adolescents. A comparison of individual CBT and family CBT for clinically anxious children found no significant differences in the proportion of anxiety-free children, quality of life, or

26 Anxiety Disorders

societal costs after a year. However, family CBT cost €299 more than individual CBT, and the data suggest individual CBT may be dominant (Bodden et al., 2008). More studies are needed both to investigate the different disorder subtypes and to compare CBT options to pharmacotherapy and usual care, to ascertain the most cost-effective strategies for each disorder type in this population.

ICER (per AFC):

€20051,993.33

The point estimates of both ICERs indicate dominance of individual over family CBT.

Panic Disorder (PD) in Adults Behavioral interventions for Panic Disorder (PD) emphasize CBT, with one trial on prevention and the remainder on treatment.

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Prevention Interventions For adults with sub-clinical Panic Disorder symptoms in the Netherlands, a time- limited CBT group intervention cost €6,198 more per prevented disorder than waiting list control after three months. This intervention had a greater than 75% likelihood of being cost-effective if a prevented disorder were valued at €10,000 (Smit et al., 2009). Data from extended time intervals would help inform how long the onset of Panic Disorder may be delayed and/or prevented by this intervention. Until then, it is up to the decision-maker to determine the willingness to pay threshold.

Treatment Interventions The first set of studies compared CBT delivery formats. One trial in Canada compared standard, group, and brief CBT for patients with moderate to severe PD with Agoraphobia. It found that all three formats were clinically effective at improving global functioning after 3 months. Additionally, the group and brief therapies incurred lower treatment costs than standard therapy. Between group and brief therapy, group CBT was more effective and somewhat less costly than standard CBT, while brief CBT appeared to be less costly and slightly less effective than standard CBT. Based on incremental cost-effectiveness ratios, brief CBT was the most cost-effective option, but based on the cost-effectiveness plane, group CBT dominated as the most cost-effective option due to its significant clinical improvement over standard CBT (Roberge et al., 2008).

Another trial compared Internet-based and group CBT for patients with PD in a psychiatric setting in Sweden. It found similar clinical outcomes for both treatment formats but lower costs for the Internet-based version, with a 75% likelihood Internet-based CBT was more cost-effective than group CBT per treatment responder (i.e. per person with 40% decrease in Panic Disorder Severity Scale score) after 6 months (Bergström et al., 2010). In general, it appears that CBT delivered in non-standard formats (e.g., brief, group, Internet-based) can be more cost-effective than the standard individualized, in-person format for PD.

The next set of studies compared CBT and antidepressant medications. A combination of CBT and selective serotonin reuptake inhibitors (SSRIs) delivered by a mental health therapist in primary care was more cost-effective than usual primary care after 12 months at $14,158 to $24,776 per QALY, well within standard willingness to pay thresholds. By another metric, this collaborative care intervention cost $8.40 per anxiety-free day (AFD). Both estimates were based on outpatient costs. In secondary analyses, including inpatient costs appeared to make the intervention cost-saving, but the precision of those estimates was lower (Katon et al., 2006).

Meanwhile, a combination of CBT and SSRIs compared to either CBT or SSRI alone in the Netherlands found that both interventions that included CBT dominated SSRI alone, but that cost-effectiveness between the two CBT versions

28 Anxiety Disorders

varied depending on the willingness to pay threshold: CBT alone was more likely to be cost-effective if the value were less than €700 per incremental improvement on an anxiety scale (Hamilton Anxiety Rating Scale). CBT plus SSRI was more likely to be cost-effective if the value were more than €700 per incremental improvement after two years (van Apeldoorn et al., 2014). Together, these studies suggest that combining CBT and SSRI appears to be more cost- effective than SSRI alone or usual care, but that whether it is more cost-effective than CBT alone will depend on the willingness to pay threshold.

Conversely, a combination of CBT and tricyclic antidepressants (imipramine) compared to either CBT or imipramine alone found either intervention alone was more cost-effective than the combined intervention in terms of incremental improvement on a panic scale (Panic Disorder Severity Scale). Further, imipramine was more cost-effective than CBT during the first 3 months of acute treatment, while CBT was more cost-effective than imipramine during both the following 6 months of maintenance treatment and the following 6 months of no treatment (McHugh et al., 2007; Barlow et al., 2000). This suggests that while antidepressants may have immediate short-term benefits, including cost- effectiveness, CBT appears to have the longer-term advantages.

For patients with PD who visit the emergency room with non-cardiac chest pain in Canada, three interventions—brief CBT limited to panic management, brief CBT, and SSRI (paroxetine)—were all more clinically effective than usual care after six months. However, between the three interventions, there were no significant differences in incremental cost-effectiveness based on an anxiety scale (Anxiety Disorder Interview Scale). Thus, whether any of them are cost-effective will depend on the decision-maker’s willingness to pay: CN$124.05 for brief CBT limited to panic management, CN$213.90 for paroxetine, and CN$309.31 for brief CBT (Poirier-Bisson et al., 2013; Lessard et al., 2012; Pelland et al., 2011).

Lastly, a Collaborative Care Management program in primary care, including SSRI (paroxetine), patient education, a consulting psychiatrist, and follow-up phone calls, was found to be cost-effective at $3 per anxiety-free day (AFD) limited to outpatient mental health costs, and cost-saving at $4 per AFD including all outpatient costs, after 12 months (Katon et al., 2002). This paralleled findings from regular and stepped Collaborative Care Management programs for anxiety disorders more generally (Joesch et al., 2012; Goorden et al., 2014). It also demonstrated similarities to the earlier intervention for Panic Disorder in primary care that combined CBT and SSRI, which cost $8 per AFD and had the potential to save costs from a broader payer perspective (Katon et al., 2006).

Table 2. Behavioral Interventions for Panic Disorder (PD) in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Prevention Interventions Smit et al. 117 persons Intervention: Probability of PP: Societal (2009) with sub- “Don’t Panic” remaining clinical Panic time-limited Panic ICER (per

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness “Don’t Panic” Disorder Cognitive Disorder-Free additional 3 preventing symptoms in Behavioral I: 86% months Panic Panic the Therapy C: 74% Disorder- Disorder via Netherlands. (CBT) group Free): time-limited 58 in therapy (9-12 €20036,198 (95% group intervention, people) for CI, 2,435 to Cognitive 59 in control. eight 2-hour 60,731) Behavioral sessions and Therapy one 2-hour Willingness to booster pay threshold: session after 3 If value is months. €10K/additio Average cost nal 3 months €750/particip free from ant. Panic Control: Disorder- Waiting list. symptoms, 75.2% Measures: probability 3 months time-limited group CBT more cost- effective than waiting list control. Treatment Interventions van 91 persons Interventions: Improvement PP: Societal Apeldoorn et (age 18-61 (1) Cognitive in Hamilton al. (2013) years) with Behavioral Anxiety Total Costs:

Panic Therapy Rating Scale I1: €20052,224 Cognitive Disorder with (CBT) for up (HAM-A): I2: €20053,118 Behavioral or without to twenty-one I1: 14.5 I3: €20053,590 Therapy, Agoraphobia 50-minute I2: 10.6 (NS) pharmacother in the sessions over I3: 16.2 apy, or the Netherlands. 12 months. (NS) I1 vs. I2: combination 52% (2) Dominant of both for experience Pharmacother d: NC 70% of time. Panic moderate or apy (SSRI) Disorder with severe with nine 20- I3 vs. I2: or without Agoraphobia. minute Dominant Agoraphobia 32 in therapist 40% of time. intervention visits over 12 #1, 27 in months plus 3 I3 vs. I1: intervention additional Better health #2, 32 in sessions outcomes and intervention during higher costs, so

30 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness #3. medication depends on tapering threshold. (weeks 40-52). (3) Willingness to Combination pay threshold: of CBT and If value SSRI for 12 <€700/increm months, in ental parallel as (1) improvement and (2). in HAM-A, CBT alone Measures: more likely to 24 months be cost- effective. If value >€700, combination of CBT and SSRI more likely to be cost-effective.

Poirier-Bisson 69 patients Interventions: Difference in PP: Societal et al. (2013), (age 19-81 (1) Brief Anxiety Lessard et al. years) with Cognitive Disorders ICER (per 1- (2012) & Panic Behavioral Interview point Pelland et al. Disorder who Therapy Schedule improvement (2011) visited the limited to (ADIS-IV): in ADIS emergency panic I1: 2.29 (2.29) score): Pharmacother department management I2: 1.95 (2.55) I1: CN$124.05 apy vs. brief for non- for one 2-hour I3: 2.00 (2.35) I2: CN$309.31 Cognitive cardiac chest session. C: 2.73 (2.34) I3: CN$213.90 Behavioral pain in Average cost (NS) (NS) Therapy for Canada. 24 in CN$174.50/p Panic intervention atient. d1: .190 I (combined): Disorder and #1, 19 in (2) Brief d2: .319 CN$187.67 non-cardiac intervention Cognitive d3: .311 chest pain in #2, 11 in Behavioral the intervention Therapy for emergency #3, 15 in seven 1-hour department control. sessions. Average costs CN$558.03/ patient. (3) Pharmacother apy

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness prescription of SSRI (paroxetine) for 6 months. Average costs CN$510.41/ patient.

Control: Usual care.

Measures: 6-month follow-up Bergström et 104 patients Intervention: Panic PP: al. (2010) with Panic Internet-based Disorder Intervention Disorder with Cognitive Severity Scale Internet-based or without Behavioral (PDSS): ICER (per vs. group Agoraphobia Therapy with I: 4.1 (4.2) treatment Cognitive within a 10 self-help C: 5.0 (5.3) responder): Behavioral psychiatric modules for I: €121 Therapy for setting in 10 weeks, d: .189 C: €500 Panic Sweden. 53 in with option to Disorder intervention, contact Percent 60 in control. therapist Treatment online and/or Responders Willingness to participate in (≥40% pay threshold: online decrease in 75% discussion PDSS scores): probability forum. I: 71% Internet-based Average cost C: 65% Cognitive €86/ Behavioral patient. Therapy (CBT) most Control: cost-effective Group than group Cognitive CBT. Behavioral Therapy for weekly 2- hours sessions for 10 weeks. Average cost €325/patient.

Measures:

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness 6-month follow-up Roberge et al. 84 patients Interventions: Panic and PP: Mental (2008) (age 19-65 (1) Standard Agoraphobia Health Care years) with Cognitive Scale (PAS): Cognitive moderate to Behavioral I1: 10.5 (11.3) Total Costs: Behavioral severe Panic Therapy for I2: 9.3 (10.3) I1:

Therapy for Disorder with 14 weekly 1- I3: 8.5 (8.7) CN$20001,411.5 Panic Agoraphobia hour sessions. 3 Disorder with in Canada. Cost d (I1 vs. I2): I2:

Agoraphobia 79% women. CN$20001,374. .111 CN$20001,262.7 30 in (2) Group d (I1 vs. I3): 5 intervention Cognitive .200 I3:

#1, 30 in Behavioral d (I2 vs. I3): CN$2000691.10 intervention Therapy .084 #2, 24 in (approx. 8 ICER (per 1- intervention people) for 14 Global point #3. weekly 1-hour Functioning improvement sessions. Cost Index (GFI) in GFI):

CN$20001,206. A composite I1: (3) Brief measure for CN$2000376.41 Cognitive clinical I2:

Behavioral significance for CN$2000248.57 Therapy for treatment I3:

seven 1-hour completers CN$2000153.58 sessions, first (n=70) across 6 5 biweekly symptom Brief and and last 2 measures. Group CBT triweekly. both have lower Cost Group CBT treatment costs was CN$2000666. and better cost- significantly effectiveness Measures: better than ratios than 3-month standard CBT standard CBT. follow-up at follow-up (p<.006). No significant differences for brief CBT. McHugh et al. 225 patients Interventions: Panic PP: (2007) & with Panic (1) Cognitive Disorder Healthcare Barlow et al. Disorder. 77 Behavioral Severity Scale (2000) in Therapy (PDSS) ICER (per 1- intervention (CBT) for Average Item unit Cognitive #1, 83 in eleven 50- Score: improvement Behavioral intervention minute 3-month acute in PDSS): Therapy, #2, 65 in sessions over phase 3-month acute

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness pharmacother intervention 12 weeks, I1: .95 (.65) phase apy, or the #3. switching to I2: .75 (.65) I1: $1,369 combination monthly I3: .60 (.61) I2: $972 of both for sessions in I3: $1,856 Panic maintenance. 6-month Disorder (2) maintenance 6-month Pharmacother phase maintenance apy with I1: .76 (.77) phase tricyclic I2: .54 (.72) I1: $1,449 antidepressan I3: .29 (.60) I2: $1,475 t (imipramine) I3: $2,634 with eleven 6-month follow- 30-minute up phase 6-month no sessions of I1: .56 (.72) treatment medication I2: .81 (.90) follow-up phase management I3: 1.11 (1.02) I1: $1,227 over 12 I2: $1,596 weeks, I3: $3,751 switching to monthly Monotherapies sessions in were always maintenance. more cost- (3) CBT plus effective than imipramine combined with 11 therapy. sessions over Pharmacothera 12 weeks (50- py more cost- minute CBT, effective in first 30-minute 3 months medication during acute management), phase, but switching to psychotherapy monthly was more cost- sessions in effective in all maintenance. longer-term phases. Measures: 3-month acute phase, 6- month maintenance phase, 6- month no- treatment follow-up phase

34 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Katon et al. 232 patients Intervention: Anxiety-Free PP: (2006) (age 18-65 Combined Days (AFDs): Healthcare years) with Cognitive I: 222.5 (95% Combined Panic Behavioral CI, 212.2 to ICER (per Cognitive Disorder in Therapy and 232.7) QALY):

Behavioral primary care pharmacother C: 162 (95% $200414,158- Therapy and across 6 apy (SSRI) CI, 149.4 to $200424,776 pharmacother clinics in U.S. delivered by a 174.5) apy for Panic 119 in mental health ICER (per Disorder intervention, therapist in d: NC AFD):

113 in control. primary care $20048.40 for up to 6 sessions in In terms of first 3 months, AFD, 94.3% and up to 6 probability the phone follow- combination of ups over next CBT and SSRI 9 months. was more costly and more Control: effective than Usual care. usual care, and 5.7% Measures: probability it 12 months was dominant.

Katon et al. 115 patients Intervention: Anxiety-Free PP: (2002) (age 18- 65 Collaborative Days (AFDs): Healthcare years) with Care model I: 230.6 (95% Collaborative Panic with SSRI CI, 193.5 to ICER (per Care for Panic Disorder in (paroxetine), 267.7) AFD): Disorder primary care increased C: 150.8 (95% Total in U.S. 58 in patient CI, 113.0 to outpatient costs

intervention, education, 188.6) -$19984 57 in control. and Total integrated on- d: NC outpatient site consulting mental health psychiatrist costs

into primary $19983 care with approx. 2 70% visits in first 3 probability months, then Collaborative brief follow- Care up phone calls Management every 3 was dominant.

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness months.

Control: Usual care.

Measures: 12 months

Obsessive-Compulsive Disorder (OCD) in Adults To date, only two trials have assessed the cost-effectiveness of behavioral interventions for OCD. Both compared alternative delivery to standard delivery of Exposure and Response Prevention (ERP), but lacked comparisons to pharmacotherapy or other alternative treatments.

Stepped care ERP, starting with low-intensity counseling and only shifting to standard intensity care if ineffective, had similar clinical outcomes to standard ERP but was less costly after 3 months. Given the similar clinical outcomes, cost- effectiveness was not calculated. However, significant differences in total costs were found both in terms of fixed dose (i.e. treatment ends when patient reaches a certain number of sessions) and the more naturalistic flexible dose (i.e. treatment ends once patient reaches predetermined criterion of clinically significant change), suggesting cost-effectiveness (Tolin et al., 2011).

Both computer-guided ERP (“BTSteps”) and standard clinician-guided ERP were more clinically effective than a relaxation placebo immediately post-treatment. Computerized ERP was significantly less effective than standard ERP. Whether computer-guided or standard ERP was more cost-effective per incremental improvement on an OCD scale (Yale-Brown Obsessive-Compulsive Scale) depended on the willingness to pay threshold: computerized ERP was more cost- effective for willingness to pay values between €58 to €192, after which standard ERP was more cost-effective (McCrone et al., 2007; Greist et al., 2002).

Table 3. Behavioral Interventions for Obsessive-Compulsive Disorder (OCD) in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Tolin et al. 30 adults with Intervention: Yale-Brown PP: Societal (2011) Obsessive- Stepped care Obsessive- Compulsive Exposure and Compulsive Total Costs Stepped care Disorder in Response Scale (Y- Fixed dose vs. standard U.S. 18 in Prevention. BOCS): (i.e. treatment Exposure and intervention, Start with I: 13.87 (6.26) ends when Response 12 in control. low-intensity C: 15.75 (6.40) patient reaches Prevention for counseling (NS) a certain Obsessive- and number of Compulsive bibliotherapy d: .297 sessions) Disorder for 3 sessions I: $3,121.65

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness over 6 weeks. Percent C: $5,222.80 If insufficient, Meeting (p<.05) shift to Criteria for traditional Significant Flexible dose intensity for Change Post- (exploratory seventeen 90- Treatment: analysis; i.e. 120 minute I: 67% treatment ends sessions twice C: 50% once patient weekly. (NS) reaches predetermined Control: criterion of Standard clinically therapist- significant administered change) Exposure and I: $2,479.62 Response C: $4,279.84 Prevention. (p<.05)

Measures: 3-month follow-up McCrone et al. 176 patients Interventions: Yale-Brown PP: (2007) & with (1) ‘BTSteps’ Obsessive- Intervention Greist et al. Obsessive- computer- Compulsive (2002) Compulsive guided Scale (Y- ICER (per 1- Disorder in Exposure and BOCS): point ‘BTSteps’ U.S. and Response I1: 19.0 (7.2) improvement computer- Canada. 55 in Prevention I2: 17.6 (6.2) on Y-BOCS): guided intervention (ERP) with C: 24.1 (6.7) I1: £64 (€92) Exposure and #1, 55 in nine steps. I2: £90 (€130) Response intervention Estimated cost d1: .734 I2 vs. I1: £133 Prevention for #2, 66 in £249 (€359) d2: 1.008 (€192) Obsessive- control. per patient. d3 (I2 vs. I1): Compulsive (2) Traditional .209 Willingness to Disorder clinician- pay threshold: guided Both For values Exposure and interventions between £40- Response were £133 (€58- Prevention significantly €192) per 1- (ERP) for 11 more effective point hour-long than relaxation improvement sessions. control on Y-BOCS, Estimated cost (p<.001), but computer- £569 (€819) computer- guided ERP per patient, guided ERP more cost- assuming was effective than

37 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness patients significantly standard ERP. attend less effective For values average 75% than clinician- above £133 of sessions. guided ERP (€192), (p=.035). standard ERP Control: more cost- Manual and effective. audiotape guidance for muscle relaxation.

Measures: Post- treatment

Post-Traumatic Stress Disorder (PTSD) in Adults To date, only one trial has assessed the cost-effectiveness of behavioral interventions for PTSD, comparing Prolonged Exposure Therapy and pharmacotherapy (sertraline) and comparing treatment preference versus no preference after one year. Prolonged Exposure Therapy dominated sertraline. Additionally, allowing choice of treatment dominated a lack of choice. Overall, providing patients their preferred choice between psychotherapy and pharmacotherapy is optimal. When choice is not possible, then Prolonged Exposure Therapy is the more cost-effective option for PTSD (Le et al., 2014).

Table 4. Behavioral Interventions for Posttraumatic Stress Disorder (PTSD) in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Le et al. (2014) 200 patients Interventions: QALY (per PP: Societal (age 18-65 (1) Prolonged patient per Optimizing years) with Exposure year): ICER (per Post- Post- Therapy for By intervention QALY): Traumatic Traumatic 10 weekly 90- I1: 0.823 I1 vs. I2 Stress Stress 120-minute I2: 0.726 Dominant Disorder Disorder. 97 sessions. Total treatment in received their cost approx. By preference Willingness to terms of treatment of $20127,033. I1 pI1: .803 pay threshold: Prolonged choice (61 in (2) I1 pI2: .844 At value of Exposure intervention Pharmacother I2 pI1: .717 $100K/QALY, Therapy vs. #1, 36 in apy I2 pI2: .744 93.2% pharmacother intervention (sertraline) probability PE apy and #2), 103 with up to 10 more cost- patient’s randomly weekly effective. treatment assigned to medication preference treatment (48 management Treatment

38 Anxiety Disorders

in sessions. Total Choice vs. No intervention cost approx. Choice

#1, 55 in $20128,653. Dominant intervention #2). Measures: Willingness to 12 months pay threshold: At value of $100K/QALY, 87.0% probability choice more cost-effective.

Social Anxiety Disorder (SAD) in Adults To date, only two trials have assessed the cost-effectiveness of behavioral interventions for Social Anxiety Disorder (SAD). Both short-term CBT and Psychodynamic Therapy (PDT) were more clinically effective with higher remission and treatment response rates than a waiting list control after 6 months. Cost-effectiveness between the two depended on the willingness to pay threshold, with CBT costing €3,615 per treatment responder and €4,958 per remitted patient and PDT costing €4,958 per treatment responder and €10,733 per remitted patient (Egger et al., 2015).

Meanwhile, an Internet-based CBT program was cost-saving compared to group CBT in terms of both QALYs ($17,823 saved per QALY) and clinically significant improvement on a social anxiety scale (Liebowitz Social Anxiety Scale; $7,046 saved per incremental improvement) after 6 months (Hedman et al., 2011). A four-year follow-up found both CBT interventions remained effective at reducing anxiety over the long term. Additionally, the Internet-based CBT remained cost- saving in terms of QALYs ($7,345 saved per QALY) although it cost $10,100 per additional person with clinically significant improvement. Overall, the willingness to pay threshold probabilities suggest the two interventions are similar in terms of cost-effectiveness (Hedman et al., 2014).

Table 5. Behavioral Interventions for Social Anxiety Disorder (SAD) in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Egger et al. 495 patients Interventions: Liebowitz PP: Societal (2015) with Social (1) Cognitive Social Anxiety Anxiety Behavioral Scale (LSAS) ICER (per Psychodynam Disorder in Therapy treatment ic Therapy Germany. 209 (CBT) for up Percent responder): and Cognitive in to thirty 50- Treatment I: €3,615 Behavioral intervention minute Responders C: €4,958 Therapy in #1, 207 in sessions. (reduction of Social Anxiety intervention Average cost ≥31% on Willingness to Disorder #2, 79 in €1,711/patient LSAS): pay threshold: control. (2) I1: 60% If value is

39 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Psychodynam I2: 52% €10K/treatme ic Therapy C: 15% nt responder, (PDT) for up CBT has to thirty 50- Percent 91.5% minute Remitted probability sessions. Patients (score and PDT has Average cost ≤30 on the 80.8% €1,666/patient LSAS): probability of I1: 36% being more Control: I2: 26% cost-effective Waiting list. C: 9% than control. If value is Measures: €16,100 for 6 months CBT and €27,290 for PDT, 97.5% probability more cost- effective.

ICER (per remitted patient): I: €5,788 C: €10,733

Willingness to pay threshold: If value is €10K/remitte d patient, CBT has 69.9% probability and PDT has 33.6% probability of being more cost-effective than control. If value is €26,605, CBT has 97.5% probability. Probability for PDT never exceeds 96%.

40 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Hedman et al. 126 Interventions: Liebowitz PP: Societal (2011) & participants (1) Internet- Social Anxiety Hedman et al. with Social based Scale (LSAS): ICER (per (2014) Anxiety Cognitive 6 months QALY): Disorder in Behavioral I1: 32.1 (23.1) 6 months

Internet-based Sweden. 64 in Therapy with I2: 40.7 (23.7) -$200917,823 vs. group intervention gradual access Cognitive #1, 62 in to 15 text d: .368 4 years Behavioral intervention modules plus -$7,345 Therapy for #2. 82% online 4 years Social Anxiety completed 4- message I1: 34.9 Willingness to Disorder year follow- access to (21.1) pay threshold: up. therapist over I2: 40.7 6 months 15 weeks. (23.6) If value is Average cost $0/QALY,

$2009464/partic d: .260 81% ipant. probability (2) Group Percent Internet-based Cognitive Clinically CBT more Behavioral Significant cost-effective Therapy for Improvement than group one (score ≤43.3 CBT. If value individual on LSAS at 6 is $40K, 79% session plus months; probability fourteen 2.5- reduction of more cost- hour group ≥14 and score effective. sessions (6-7 ≤44 on LSAS people) over at 4 years): 4 years 15 weeks. 6 months If value is $0/ Average cost I1: 64% QALY, 62%

$20092,687/part I2: 45% probability icipant. (NS) Internet-based CBT more Measures: 4 years cost-effective 6-month I1: 56% than group follow-up & I2: 65% CBT. If value 4-year follow- (NS) is $100K, 64% up probability more cost- effective.

ICER (per person with clinically significant improvement)

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness : 6 months

-$20097,046

4 years $10,100

Willingness to pay threshold: 6 months If value is $0/ additional improved patient, 81% probability Internet-based CBT more cost-effective than group CBT. If value is $3K, 89% probability more cost- effective.

4 years If value is $0/additional improved patient, 62% probability Internet-based CBT more cost-effective than group CBT. If value is $100K, 22% probability more cost- effective.

Multiple Types of Anxiety Disorders in Adults As reviewed thus far, most studies of anxiety disorders in adults focus on specific disorder subtypes. However, some studies combine multiple subtypes, look at clinical anxiety more generally, or include anxiety and depression

42 Anxiety Disorders

populations together. As a note, while no studies focused exclusively on Generalized Anxiety Disorder, it is included in some of these mixed studies.

In these studies a major focus is to improve cost-effectiveness of care delivery, often in primary care, for proven treatment options. Successful techniques include Collaborative Care Management, stepped care models, and telehealth programs. However, a more general intervention in Germany to optimize care for clinical anxiety by training general practitioners on diagnosis and treatment and providing a psychiatric consultant-liaison in primary care was dominated by usual care with no significant improvement on anxiety levels, associated costs, or quality of life after nine months (König et al., 2009).

Both regular and stepped Collaborative Care Management in primary care were cost-effective. The CALM (Coordinated Anxiety and Learning Management) Collaborative Care program included a choice of CBT, anti-anxiety medication, or both, along with care managers to monitor outcomes, adherence, and optimization. CALM was cost-effective for patients with Generalized Anxiety Disorder, Panic Disorder, Post-Traumatic Stress Disorder, and/or Social Anxiety Disorder with or without Major Depression in both English- and Spanish- speaking populations, at $4,900 per QALY or about $4.29 per additional anxiety- free day (AFD) after 18 months (Joesch et al., 2012; Roy-Byrne et al., 2010).

Similarly, stepped Collaborative Care Management for Generalized Anxiety Disorder and Panic Disorder in primary care in the Netherlands, starting with guided self-help, then CBT, then antidepressants if needed, was clearly dominant as cost-saving after one year. Moreover, it remained cost-effective at only €6,965 per QALY, within standard willingness to pay thresholds, even when excluding lost productivity costs (Goorden et al., 2014).

For patients with anxiety disorders in primary care in Sweden, Internet-delivered CBT, with online therapist support tailored to address any psychiatric comorbidities and patient preferences, remained significantly more clinically effective than a waiting list control after a year, and was cost-saving in terms of health-related quality of life ($7,523 saved per QALY) and clinical improvements ($1,824 saved per improved patient) at post-treatment (Nordgren et al., 2014).

For patients who visit the emergency department and are discharged with anxiety disorder diagnoses, a stepped care program first mailed a letter with more information about anxiety and treatment options. If the patient visited the emergency department again, a case manager provided an outreach call as well as follow-up calls as needed. After six months, the intervention was cost-saving over usual care at $7.01 saved per person per month (Kolbasovsky et al., 2007). These cost findings are better than for CBT and medication, as shown in a similar study described earlier for patients with Panic Disorder who visited the emergency department for non-cardiac chest pain (Poirier-Bisson et al., 2013).

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Table 6. Behavioral Interventions for Multiple Types of Anxiety Disorders in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Nordgren et 100 patients Intervention: Clinical PP: Societal al. (2014) with primary Internet- Outcomes in diagnosis of delivered Routine ICER (per Individually- an anxiety Cognitive Evaluation- QALY): tailored disorder with Behavioral Outcome -$7,523 Internet- or without Therapy Measure delivered psychiatric tailored to (CORE-OM): Cognitive comorbidities address I: 10.97 (SE Willingness to Behavioral in primary comorbidities 0.75) pay threshold: Therapy for care in and C: 17.65 (SE If value is anxiety Sweden. 50 in preferences of 0.63) $0/QALY, disorders in intervention, patient for 7- 90% primary care 50 in control. 10 weekly d: 1.369 probability with or individually Internet- without assigned Beck Anxiety delivered comorbidities modules Inventory Cognitive guided by (BAI): Behavioral online I: 11.81(SE Therapy more therapists. 1.10) cost-effective Average cost C: 16.30(SE than waiting $507/particip 1.10) list. If value is ant. $3K, 95% d: .577 probability. Control: Waiting list. Percent ICER (per Average cost Clinically additional $68/participa Significant improved nt. Improvement patient): (based on -$1,824 Measures: CORE-OM): Post- I: 46% Willingness to treatment C: 12% pay threshold: If value is $0/ No moderating improved effect of patient, 95% comorbidities probability on outcomes. Internet- Effects Cognitive persisted at 1- Behavioral year follow-up Therapy more for primary and cost-effective secondary than waiting outcome list. If value is measures. $1K, 99% probability.

44 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Goorden et al. 180 patients Intervention: Quality of Life PP: Societal (2014) with Stepped Utility Score Generalized Collaborative (EuroQOL): ICER (per Stepped Anxiety Care I: .80 (.19) QALY): Collaborative Disorder or Management C: .73 (.29) With Care Panic with productivity Management Disorder evidence- d: .292 costs for across 43 based steps: 1) Dominant Generalized primary care Guided self- Anxiety practices in help, 2) Without Disorder and the Cognitive productivity Panic Netherlands. Behavioral costs Disorder in 114 in Therapy, 3) €6,965 primary care intervention, antidepressan 66 in control. ts via Willingness to medication pay threshold: algorithm and If value is medication €10K/QALY, optimization. 100% probability Control: stepped Usual care. Collaborative Care Measures: Management 12 months more cost- effective than usual care if including productivity costs, and >90% probability more cost- effective if not including productivity costs. Joesch et al. 692 patients Intervention: Brief PP: (2012) & Roy- (age 18-75 CALM Symptom Healthcare Byrne et al. years) with Collaborative Inventory (2010) Generalized Care (BSI-12): ICER (per Anxiety Management I: 8.21 (95% QALY):

Coordinated Disorder, program with CI, 7.43 to $20094,900 Anxiety Panic choice of 8.98) Learning and Disorder, Cognitive C: 9.84 (95% Willingness to Management Post- Behavioral CI, 9.05 to pay threshold:

45 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness (CALM) in Traumatic Therapy 10.62) If value is primary care Stress (CBT), anti- (p=.05) ≥$2.5K-$5K/ Disorder, anxiety QALY, INB and/or Social medication, or d: NC can be Anxiety both; real- positive. If Disorder with time outcomes Highly value is or without monitoring; significant at 6 $35K/ Major computerized and 12 months QALY based Depression CBT (p<.001). on the SF-6D across 17 assistance; or $90K/ primary care care managers Anxiety-Free QALY based clinics in U.S. for medication Days (AFDs): on the EQ-5D, English- and adherence I: 409.2 (95% 95% Spanish- and CI, 392.3 to probability speakers. 351 medication 426.1) positive. in optimization. C: 352.1 (95% intervention, Length 3-12 CI, 332.2 to ICER (per 341 in control. months. 371.9) AFD):

Average $20094.29 additional d: NC cost Willingness to $245/patient. pay threshold: If value is Control: ≥$4/AFD, Usual care. INB can be positive. If Measures: value is 18 months ≥$30/AFD, INB is always positive. König et al. 327 patients Intervention: Beck Anxiety PP: Societal (2009) with clinical Optimized Inventory anxiety across Care model in (BAI): ICER (per Optimized 46 primary primary care, I: 18.18 (12.17) QALY): Care model care practices includes 10- C: 16.72 Dominated for anxiety in Germany. hour training (10.34) (€2006347,381) disorders in 169 in for general (NS) primary care intervention, practitioners Willingness to 158 in control. on diagnosis d: .130 pay threshold: and treatment If value is plus <€50K/QALY psychiatric , only 2% consultant- probability liaison service Optimized for 6 months. Care model is Average cost more cost-

46 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness €11.75/partici effective than pant. usual care.

Control: Usual care.

Measures: 9-month follow-up Kolbasovsky 607 adults Intervention: Frequency of PP: et al. (2007) discharged Stepped care ED Visits: Healthcare from the intervention I: 41% Reducing the emergency with letter C: 63% Average ED number of department after initial Cost Per emergency (ED) with ED visit of Average Person: department anxiety educational Number of I: $70.63 visits diagnoses in information Additional ED (246.50) associated U.S. 307 in about anxiety Visits Per C: $118.15 with anxiety intervention, and treatment Person: (326.67) 300 in control. options. If I: .26 (.90) another visit C: .39 (1.02) Average to ED, Psychiatric outreach d: .135 Outpatient phone call Cost Per with case Average Person: manager, with Number of I: $214.75 follow-up Additional (460.99) calls as Psychiatric C: $209.24 needed. Visits Per (474.65) Person: Control: I: 2.60 (5.50) Average Cost Usual care. C: 2.67 (6.07) Savings Per Person Per Measures: d: .012 Month: 6-month $7.01 follow-up The intervention had lower costs for ED visits. The psychiatric outpatient costs were not significantly different.

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Anxiety Disorders in Older Adults To date, there have been four trials for the cost-effectiveness of behavioral interventions for anxiety disorders in older adults (age 60 years and older). Two were focused on prevention in high-risk older adults, one for treatment of anxiety disorder more generally, and one for a specific phobia of falling.

Prevention Interventions For prevention in older adults with subclinical symptoms of anxiety or depression in the Netherlands, two stepped care programs to prevent the onset of diagnosable anxiety and depressive disorders demonstrated conflicting results. In the first, a nurse-provided stepped care program with four steps (watchful waiting, bibliotherapy, problem-solving, antidepressant medication) led to half as many anxiety or depressive disorder diagnoses as routine care after one year (11.6% versus 23.8%). This could be cost-effective at €4,367 per anxiety- or depression-free year, depending on the willingness to pay threshold (van’t Veer-Tazelaar et al., 2010; van’t Veer-Tazelaar et al., 2009).

The second focused on older adults in residential homes and was provided by the residential staff. Here, a stepped care program (watchful waiting, bibliotherapy, life review, and general practitioner consult to consider antidepressants or referral to a mental health specialist) did not produce any significant differences in clinical outcomes or associated costs as compared to usual care. The differences in incidence of anxiety and depressive disorders combined were also almost identical to usual care (20% versus 19%), and the intervention was not cost-effective in terms of QALYs, reduced incidence, or improved symptoms (Bosmans et al., 2014). The biggest difference between the two studies was that the former was conducted in the community and the latter in residential homes, but it is unclear how this would explain the conflicting findings.

Treatment Interventions For older adults with stress and anxiety symptoms in Australia, therapist-guided Internet-delivered Cognitive Behavioral Therapy was significantly more clinically- and cost-effective than a waiting list for all patients at post-treatment and up to a year later. This was true for patients who did and did not meet clinical threshold at baseline. The intervention cost $8,806 per QALY, which had a greater than 95% likelihood of being cost-effective at the standard willingness to pay threshold of $50,000 (Dear et al., 2015).

For a Specific Phobia (fear of falling) in older adults in the Netherlands, a multicomponent nurse-led cognitive behavioral group program was significantly more effective than usual care at reducing both fear of falling and activity avoidance. This program could be cost-effective at €1,070 per person who no longer feared falling or €683 per person who no longer avoided activities, depending on the willingness to pay thresholds (van Haastregt et al., 2013).

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Table 7. Behavioral Interventions for Anxiety Disorders in Older Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Prevention Interventions Bosmans et al. 185 older Intervention: Incidences: PP: Societal (2014) adults Stepped care Anxiety screened for program to Disorder(s) ICER (per sub-threshold prevent onset I: .13 (SE .05) QALY): Stepped care anxiety and of anxiety and C: .05 (SE .03) €200826,890 program to depression depressive (NS) prevent symptoms disorders with Willingness to anxiety and across 14 1 month of d: .208 pay threshold: depression for residential watchful older adults in homes in the waiting then Depression If value is residential Netherlands. 3-month and/or Anxiety €0/QALY, homes 93 in cycles (self- I: .20 (SE .06) 13% intervention, help module C: .19 (SE .05) probability 92 in control. with coaching, (NS) stepped care 49% with cost life review, program more data. and general d: .019 cost-effective practitioner than usual consults for Improvement care. At antidepressan on Hospital highest ts or therapist and Anxiety threshold, the referral). Total Depression max. 85% costs €838 Scale (HADS): probability. higher than I: 1.3 (SE .41) control (NS). C: .66 (SE .02) ICER (per (NS) incidence of Control: anxiety): Usual care. d: .309 € 10,328 2008

Measures: ICER (per 10-month No difference in incidence of follow-up incidence of disorders or depression or any other anxiety): outcomes. €200885,521

ICER (pre incremental improvement in HADS-A):

-€2008963 van’t Veer- 170 elderly Intervention: Percent With PP: Societal Tazelaar et al. persons (age Preventive Diagnosable (2010 & 2009) 75+ years) stepped care Disorder: ICER (per with program in 3- I: 11.6% anxiety-/

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Stepped care subthreshold month cycles C: 23.8% depression- to prevent levels of with 4 steps free year): anxiety and anxiety or (watchful €20074,367 depression for depressive waiting, ICER (per 50% high-risk symptoms in bibliotherapy, reduced risk individuals in the problem- of disorder late life Netherlands. solving, onset):

74% women. antidepressan €2007532 50% with 2+ ts). Cost chronic varied based Willingness to conditions. 86 on steps, but pay threshold: in average cost If value is

intervention, €2007563.42/pa €5K/anxiety- 84 in control. rticipant. or depression- free year, 57% Control: probability Routine stepped care primary care. program more cost-effective Measures: than routine 12-month primary care, follow-up if value is €10K-€20K, 86%-94% probability more cost- effective. Treatment Interventions Dear et al. 72 older Intervention: Generalized PP: (2015) adults (age Internet- Anxiety Healthcare 60+ years) delivered Disorder 7- Therapist- experiencing Cognitive Item Scale ICER (per guided symptoms of Behavioral (GAD-7): QALY): Internet- stress and Therapy over I: 3.90 (2.94) $8,806 (95% delivered anxiety in 8 weeks with C: 9.75 (4.91) CI, 2,849 to Cognitive Australia. 35 brief weekly (p<.001) 39,522) Behavioral in contact with a Therapy for intervention, clinical d: 1.490 Willingness to older adults 37 in control. psychologist pay threshold: with via telephone Patient Health If value is symptoms of or secure Questionnaire $8,806/QALY, anxiety email. -9 Item (PHQ- 50% Average total 9): probability therapist time I: 3.63 (2.68) Internet- 58 minutes. C: 10.47 (4.62) delivered (p<.001) Cognitive

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Control: Behavioral Waiting list. d: 1.874 Therapy more cost-effective Percent than waiting Measures: Reliable list control. If Post- Improvement: value is $50K, treatment I: 78.9%-82.6% >95% C: 13%-18.5% probability (p<.001) more cost- effective. Percent Reliable Recovery (shifted from above clinical cut-off to below it): I: 73%-78% C: 13-18% (p<.001)

Differences persisted at 3 months and 12 months and remained significant when limited to the clinical sample. van Haastregt 381 elderly Intervention: Percent No PP: Societal et al. (2013) adults (age Multicompon Longer Afraid 70+) who ent nurse-led of Falling: ICER (per “A Matter of reported fear cognitive I: 23.5% person no Balance” of falling (a behavioral C: 14.4% longer afraid intervention Specific group (p=.016) of falling): to reduce fear Phobia) in the program for 8 €20041,070 of falling Netherlands. weekly 2-hour Percent No 187 in sessions and 1 Longer ICER (per intervention, booster Avoiding person no 194 in control. session. Activity: longer Average cost I: 37.4% avoiding €276/ C: 23.2% activity):

person. (p=.002) €2004683

Control: For fear of

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Usual care. falling, 44% probability Measures: intervention 14-month was dominant. follow-up For activity avoidance, 45% probability intervention was dominant.

Anxiety Disorders in Medical Populations Anxiety in medical populations manifests in two ways: as Health Anxiety or Hypochondriasis, which refers to excessive health concerns with or without somatic complaints, and as co-occurring anxiety disorders and medical disorders.

Health Anxiety (Hypochondriasis) All studies reviewed for Health Anxiety included Cognitive Behavioral Therapy (CBT), one with a version customized for Health Anxiety (CBT-HA). Two studies assessed patients with excessive Health Anxiety in outpatient health clinics in the United Kingdom. In one, hospital-based therapist-delivered CBT-HA cost £14,169 per QALY compared to standard care after two years, which was within typical willingness to pay thresholds. However, cost-effectiveness remained uncertain due to variability in the data that resulted in large confidence intervals and very small differences in health-related quality of life (Tyrer et al., 2014). Meanwhile, in a single genitourinary clinic, brief CBT with bibliotherapy was potentially cost-effective compared to usual care at £33 per incremental improvement on a health anxiety scale (Health Anxiety Inventory). Cost- effectiveness would depend on the willingness to pay threshold (Seivewright et al., 2008).

Lastly, Internet-based CBT for severe health anxiety in Sweden was clinically effective and appeared to be cost-saving at £6,533 per QALY and £1,244 per remission compared to an online discussion forum after one year. Looking at the cost-effectiveness planes, the intervention had a greater than 60% probability of being cost-effective in terms of QALYs or remissions, even if the willingness to pay thresholds were zero (Hedman et al., 2013). Importantly, the Internet-based version was not compared to other forms of CBT or to usual care.

Table 8. Behavioral Interventions for Health Anxiety in Medical Populations Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Tyrer et al. 342 patients Intervention: Mean PP: (2014) (age 16-75 Cognitive Improvement Healthcare years) Behavioral on Health and Social Cognitive experiencing Therapy Anxiety Services

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Behavioral excessive adapted for Inventory Therapy for Health Health (HAI): ICER (per Health Anxiety in a Anxiety (CBT- I: 5.90 (7.54) QALY):

Anxiety in range of HA) delivered C: 3.66 (6.57) £200914,169 medical secondary by hospital- (p=.0030) patients care clinics based Insufficient (CHAMP) (e.g., cardiac, therapists for d: .318 evidence to endocrine) 5-10 sessions draw strong across 6 and option of HAI differences conclusions hospitals in booster were clinically that CBT-HA UK. 172 in sessions. significant at is more costintervention, Average cost p<.0001 at 6 effective than

170 in control. £2009421.51/pat and 12 months. standard care, ient. due to large Mean confidence Control: Improvement intervals in Standard care. on Hospital estimates. Anxiety and Measures: Depression ICER (per 2 years Scale (HADS- improvement A): on HAI):

I: 3.33 (4.57) £200955.86 C: 2.07 (4.35) (p=.0137) Willingness to pay threshold: d: .283 If value is >£53/per improvement in HAI, >50% probability CBT-HA is more cost- effective than standard care. Hedman et al. 75 Intervention: Health PP: Societal (2013) participants Internet-based Anxiety with severe Cognitive Inventory ICER (per Internet-based Health Behavioral (HAI): QALY):

Cognitive Anxiety in Therapy, I: 60.3 (27.2) −£20106,533 Behavioral Sweden. 39 in including 12- C: 68.5 (28.4) Therapy for intervention, module self- Willingness to severe Health 36 in control. help text for d: .295 pay threshold: Anxiety 12 weeks. If value is Beck Anxiety £0/QALY, Control: Inventory 67% Attention (BAI): probability

53 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness control with I: 10.0 (9.4) Internet-based an online C: 15.2 (12.1) CBT more discussion cost-effective forum for 12 d: .484 than online weeks. discussion Percent forum. If Measures: Remission value is £5K/, 1-year follow- Post- 77% up Treatment (i.e. probability no longer more cost- meet effective. diagnostic criteria for ICER (per Health additional Anxiety): remission):

I: 67.5% −£20101,244 C: 4.9% (p<.001) Willingness to pay threshold: If value is £0/remission, 64% probability Internet-based CBT more cost-effective than online discussion forum. If value is £5K, 96% probability more cost- effective. Seivewright et 41 patients Intervention: Significantly PP: al. (2008) with high Brief greater Healthcare Health Cognitive clinical Cognitive Anxiety in a Behavioral improvement Total Costs:

Behavioral genitourinary Therapy for I: £2005911 (560) Therapy for clinic in the supplemented intervention C: £2005634 Health UK. 18 in with group for the (602) Anxiety in a intervention, bibliotherapy following (NS) genitourinary 23 in control. for 0-13 measures: clinic sessions Health ICER (per 1- (average 4.3) Anxiety point over 6-9 Index; improvement

54 Anxiety Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness months. Hospital in HAI):

Average cost Anxiety and £200533 £427/patient. Depression Scale-Anxiety; Control: Hospital Usual care Anxiety and (option to Depression enroll in CBT Scale- after 1 year) Depression (p<.05) Measures: 12 months

Co-Occurring Medical Conditions Anxiety often occurs concurrently with other medical conditions, which can complicate illness progression and treatment. Three studies examined interventions comorbid with another medical condition. With one study each for patients with anxiety plus either asthma, cancer, or coronary heart disease, it is difficult to draw meaningful conclusions on cost-effective solutions at this time. Findings differ depending on the disorder.

For highly anxious asthma patients in the United Kingdom, a cognitive behavioral intervention to improve self-management of anxiety produced no significant differences in either asthma-related fear or the associated costs compared to routine clinical care after six months. This indicates this intervention would not be cost-effective (Parry et al., 2012). Conversely, a second study examined group CBT for highly anxious cancer patients in an inpatient rehabilitation program in Germany. The CBT program included confronting patients with their fears. This CBT program was highly cost-saving after 12 months based on two different measures (Fear of Progression and Health Survey Mental Score) when compared to non-directive and unspecific group therapy. Both measures indicated a greater than 90% likelihood that group CBT would be more cost-effective than the general group therapy without additional costs, although it was not compared to usual care (Sabariego et al., 2011).

A third study examined a brief cognitive behavioral intervention (HeartOp Programme) for preoperative patients about to undergo elective coronary bypass graft surgery in the United Kingdom. These patients are known to have high psychological distress and limited physical activity. The HeartOp Programme was a supplement to routine nurse counseling and focused on improving mental health and reducing cardiac misconceptions. The HeartOp program produced no significant differences in anxiety symptoms, but was highly cost-effective at only £288.83 per QALY after eight weeks. The program had a greater than 90% likelihood of being cost-effective at a standard willingness to pay threshold of £30,000 (Furze et al., 2009).

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Table 9. Behavioral Interventions for Anxiety Disorders in Medical Populations Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Parry et al. 59 highly Intervention: Asthma PP: (2012) anxious Cognitive Symptom Healthcare patients with behavioral Checklist - Cognitive asthma in UK. intervention Panic Fear Frequency of behavioral 28 in to improve Sub-Scale service use intervention intervention self- (ASC-PF): for anxiety (15 completed management I: 20.78 (8.07) General complications treatment), 31 of anxiety, C: 24.83 (7.71) Practice with asthma in control. particularly (NS) Consultations: asthma- I: 1.8 (1.5) specific fear. d: .513 C: 2.08 (3.1) 1.5-hour intro (NS) session, 4-6 one-hour Total Primary sessions, and Care Contacts: optional two I: 1.87 (1.73) 1-hour follow- C: 2.27 (3.1) up sessions. (NS) Average cost £378-£798/ Number of participant. Prescribed Medications: Control: I: 1.27 (1.3) Routine C: 1.00 (1.3) clinical care. (NS)

Measures: 6-month follow-up Sabariego et 174 cancer Intervention: Fear of PP: Societal al. (2011) patients with Group Progression high levels of Cognitive Questionnaire ICER (per unit Group anxiety in 3- Behavioral (FoPQ): of Cognitive week Therapy of I: 10.07 (2.48) improvement Behavioral inpatient four 90- C: 9.73 (2.23) on FoPQ): Therapy for rehabilitation minute Dominant dysfunctional program in sessions d: -.144 (- fear in cancer Germany. 91 aimed at €200478,741.66) patients in confronting Mental Score intervention, patients with (MCS) of the Willingness to 83 in control. their fears. Health Survey pay threshold: Average cost (SF-12): 92.4% €47/patient. I: 43.3 (11.4) probability C: 42.6 (9.4) group CBT Control: more cost-

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Client- d: -.067 effective than centered, non-directive supportive- therapy experiential without but non- additional directive and cost. unspecific group therapy ICER (per unit of four 90- of minute improvement sessions. on Fear of Average cost MCS): €47/ Dominant

patient. (-€200416,976)

Measures: Willingness to 12-month pay threshold: follow-up 96.5% probability group CBT more cost- effective than non-directive therapy without additional cost. Furze et al. 182 Intervention: Difference in PP: (2009) preoperative Routine nurse State Trait Healthcare patients counseling Anxiety HeartOp waiting for plus HeartOp Inventory ICER (per Programme first time Programme of (STAI): QALY): prior to elective brief cognitive 1.07 (95% CI, - £2004288.83 coronary coronary behavioral 1.98 to 4.12) bypass graft bypass graft intervention, (NS) Willingness to surgery to surgery in including a 2- pay threshold: reduce UK. 88 in part booklet, If value is psychological intervention, relaxing <£30K/QALY symptoms 94 in control. program, , >90% goals diary, probability and facilitator HeartOp follow-up via Programme phone. more cost- Average cost effective than

of £20041.73/ routine nurse patient. counseling

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness alone. Control: Routine nurse counseling, including facilitator follow-up via phone.

Measures: 8-week follow-up

LIMITATIONS AND FUTURE DIRECTIONS Given the comparable clinical efficacy of pharmacotherapy and psychotherapy, cost-effectiveness research could help determine the optimal economic course of action for different populations. Other than for Panic Disorder, few studies compared these two options directly. Notably, studies of behavioral interventions often do not exclude patients who are already on a stable dose of medication. Conducting analyses on these subsets of patients within existing datasets may also be informative.

While anxiety disorders are one of the most studied neuropsychiatric disorders for cost-effectiveness, the available data are still quite limited. More studies are needed to better distinguish between general anxiety symptoms and diagnosable disorders. While studies of both are valuable, further research is needed to hone in on the most effective strategies for each type of disorder. Moreover, given the tremendous variation for each subtype, it is also important to conduct studies limited to each population. Panic Disorder was the most studied, while there were no studies focused exclusively on Generalized Anxiety Disorder. Meanwhile, only a few studies were available for Obsessive-Compulsive Disorder, Post-Traumatic Stress Disorder, Social Anxiety Disorder, and Specific Phobia.

Research indicates that anxiety disorders have a relatively early age of onset compared to other chronic conditions, yet only one study tested an intervention for anxiety disorders in children and adolescents. Interventions targeted at younger populations are likely to have broad economic benefits, particularly on reducing indirect costs of secondary outcomes and productivity losses across the lifespan. Given the high chronicity of anxiety disorders, both studies of longer duration as well as metrics to assess how long clinically meaningful effects last would allow for more precise estimates on the associated economic benefits. This information may support the development of more cost-effective interventions.

Finally, anxiety disorders are the most comorbid neuropsychiatric disorder. More studies are needed in older adults and medical populations to better

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illuminate cost-effective interventions that may be able to impact multiple health outcomes simultaneously. The few available studies showed opposing cost- effectiveness outcomes for elevated anxiety in various medical populations. This reinforces the need for further refinement between different conditions.

KEY POINTS • For children and adolescents, one study found no clinical or cost differences between individual or family Cognitive Behavioral Therapy (CBT) after one year. However, it concluded that individual CBT may dominate family CBT as it tended to be slightly more effective and slightly less expensive. It was not compared to pharmacotherapy or usual care.

• For Panic Disorder, most interventions are CBT-based and cost-effective. o In-person CBT alone or combined with antidepressants was more cost- effective than antidepressants alone or usual care. However, antidepressants alone could be more cost-effective for short-term benefits. Cost-effectiveness between CBT alone and CBT combined with antidepressants varied depending on the willingness to pay threshold. o Different delivery formats of CBT were more cost-effective than standard CBT. Group CBT appeared more cost-effective than brief CBT due to greater clinical improvements, and Internet-based CBT appeared to be more cost-effective than group CBT due to lower costs. • For Obsessive-Compulsive Disorder (OCD), alternative delivery of Exposure and Response Prevention (ERP) appeared more cost-effective than standard delivery, but lacked comparisons to pharmacotherapy or other treatments. o Stepped care Exposure and Response Prevention (ERP), starting with lower-intensity counseling and only shifting to standard intensity if ineffective, was equally effective and less expensive than standard ERP. o Computer-guided ERP was more cost-effective than standard ERP at lower willingness to pay values and standard ERP was more cost-effective at higher willingness to pay values due to its significantly greater clinical effectiveness.

• For Posttraumatic Stress Disorder (PTSD), one study found patient choice for treatment between psychotherapy and pharmacotherapy dominated no choice. If choice cannot be provided, it also found that Prolonged Exposure Therapy dominated pharmacotherapy (sertraline).

• For Social Anxiety Disorder (SAD), in-person psychotherapy depended on the willingness to pay threshold but Internet-based CBT was cost-effective. o CBT cost €3,615 per treatment responder and €4,958 per remitted patient. Psychodynamic Therapy cost €4,958 per treatment responder and €10,733 per remitted patient compared to no intervention after 6 months. o Internet-based CBT was cost-saving over group CBT both after 6 months and after 4 years.

• For Health Anxiety, different CBT formats were potentially cost-effective.

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o In-person CBT appeared cost-effective, but cost-effectiveness remained uncertain due to variability in the data. o Brief CBT might be cost-effective, depending on the willingness to pay threshold. o Internet-based CBT was cost-saving compared to an online discussion forum. It was not compared to other forms of CBT or standard care.

• For comorbid medical populations, the cost-effectiveness of CBT-based interventions varied for interventions addressing different medical comorbidities. More studies of interventions targeting populations with each medical disorder are needed to draw meaningful conclusions. o For highly anxious asthma patients, a cognitive behavioral intervention to improve self-management of anxiety was not cost-effective. o For highly anxious cancer patients, group CBT was cost-saving for improved symptoms compared to non-directive and unspecified group therapy. It was not compared to other formats of CBT or usual care. o For preoperative patients about to undergo elective coronary bypass graft surgery, a brief cognitive behavioral intervention was highly cost-effective after eight weeks.

• Among emergency room interventions for patients with anxiety disorders, a stepped care intervention, but not CBT or medication interventions, was cost- saving. o Based on one study, a stepped care intervention, with a mailed letter and then phone calls if needed, was cost-saving per patient per month. o Based on one study, brief CBT (limited to panic management or not) or SSRI (paroxetine) were clinically effective but cost-effectiveness would depend on the willingness to pay threshold.

• For older adults, therapist-guided Internet-based CBT was cost-effective for anxiety symptoms. Multi-component group CBT had the potential to be cost- effective for a Specific Phobia (fear of falling), depending on the willingness to pay thresholds.

• For improving care delivery systems in primary care across anxiety disorders, almost all interventions were cost-effective. o Optimizing Care by providing additional training to primary care physicians and providing access to a psychiatric consultant-liaison was the only intervention that was dominated by usual care after 9 months. o Both traditional and stepped Collaborative Care Management programs in primary care—including options for CBT and/or antidepressants— were cost-effective for multiple anxiety disorders, including one specifically for Panic Disorder, compared to usual care. o Telehealth-based CBT interventions, with or without minimal therapist support, were cost-effective across multiple types of anxiety disorders.

• For prevention of anxiety disorders, CBT and stepped care programs may or may not be cost-effective.

60 Anxiety Disorders

o For sub-clinical symptoms of Panic Disorder, time-limited group CBT had a greater than 75% likelihood of being cost-effective if the value of a prevented disorder were €10,000 for this time period. o For older adults with subclinical symptoms, stepped care programs to prevent the onset of depressive and anxiety disorders had conflicting findings, one with the potential to be cost-effective depending on the willingness to pay threshold, and the other demonstrating no differences in clinical outcomes or costs.

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66 Depression

CHAPTER 2: DEPRESSIVE DISORDERS

ABSTRACT Depression is a leading cause of disease burden globally. In the United States, it is estimated that 16.2% of the population will experience at least one depressive episode. In sum, depressive disorders in the United States are estimated to cost $83.1 billion per year. This includes direct costs (e.g., increased use of health services) and indirect costs (e.g., reduced workplace productivity).

While medication is often first-line treatment, several psychosocial interventions may prove to be cost-effective alternatives or additions. For children and adolescents, Cognitive Behavioral Therapy may be more cost-effective than usual care for primary prevention in high-risk youth, but does not appear more cost- effective than antidepressant medication for treatment. However, studies over longer duration are needed. For adults, in-person Interpersonal Therapy (IPT) and Cognitive Behavioral Therapy (CBT) appear more cost-effective than usual care but not antidepressant medication. However, CBT may be more cost- effective for specific subpopulations (e.g., treatment-resistant depression, relapse prevention, adjunctive care). Moreover, non-standard delivery formats in primary care including Collaborative Care Management and telehealth-based therapies with or without professional support have consistently demonstrated cost-effectiveness over usual care across multiple populations. However, studies comparing these formats to antidepressant medication and in-person therapies are needed.

Brief therapy-based treatments including Minimal Contact Psychotherapy and Cognitive Self-Therapy may be more cost-effective than usual care, but not more cost-effective than CBT for prevention and treatment, but more data are needed. On the other hand, generic or non-directive therapy, short-term counseling, and supportive care were not more cost-effective than usual care, CBT, or antidepressant medication. For postnatal women at high risk for depression, psychologically-informed interventions were more cost-effective than usual care, although more data are needed.

For high-risk older adults, stepped care prevention programs had conflicting results. For treatment in older adults, results paralleled the general population. Significantly, psychotherapeutic treatments in adults with co-occurring medical disorders (e.g. coronary disease, diabetes) were cost-effective or even cost-saving. While psychosocial treatments may not be more cost-effective than antidepressant medication alone, adjunctive psychosocial treatment via Collaborative Care Management, brief therapy, or telehealth-based therapy, particularly in comorbid medical populations, will likely have long-term economic benefits.

BACKGROUND ON DISORDER Depressive disorders are common and treatable but debilitating neuropsychiatric disorders. They extend beyond sadness and include changes such as a loss of interest or pleasure, weight loss or gain, insomnia or oversleeping, loss of energy,

67 Depression agitation, irritability, feelings of worthlessness or excessive guilt, difficulty concentrating, indecisiveness, and recurrent thoughts of death or suicide.

The American Psychiatric Association recently issued their revised Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which added two new depression-related diagnoses. Most cost-effectiveness studies focused on Major Depression or substantial depressive symptoms, but official classifications include:

• Major Depressive Disorder is characterized by some combination of the traits above plus functional impairment such as the inability to sleep, eat, work, and/or enjoy life for at least six weeks. Persons with Major Depression may experience a single episode or recurrent episodes throughout their lifetime.

• Persistent Depressive Disorder (combining former diagnoses of Chronic Major Depressive Disorder and Dysthymic Disorder) is characterized by a chronic depressive mood that lasts for at least two years. The severity of symptoms may vary, with ‘dysthymia’ indicating mild chronic depressive symptoms. Some studies include the former diagnosis of Dysthymic Disorder.

• Major Depressive Disorder with Seasonal Pattern (formerly Seasonal Affective Disorder) is a sub-diagnosis of Major Depression that is characterized by the onset and remission of depressive symptoms depending on time of year. Most commonly, onset is in fall or winter and remission in spring. No cost-effectiveness studies are currently available.

• Major Depressive Disorder with Peripartum Diagnosis (formerly Postpartum Depression) is a sub-diagnosis of Major Depression that is characterized by the onset of depressive symptoms during pregnancy or the first four weeks after delivery. One study includes the former diagnosis of Postpartum Depression.

• Premenstrual Dysphoric Disorder is a new diagnosis for women that is characterized by the experience of depressive symptoms including irritability and tension about five to eleven days before commencement of the monthly menstrual cycle. No cost-effectiveness studies are currently available.

• Disruptive Mood Dysregulation Disorder is a new diagnosis for children that is characterized by persistent irritability and frequent episodes of extreme behavioral dyscontrol in young people up to the age of 18 years. No cost- effectiveness studies currently available.

Generally, the term ‘depression’ refers to Major Depressive Disorder. Additionally, terms like ‘minor depression’ and ‘subthreshold depression’ are used to indicate persons with significant depressive symptoms who do not meet diagnostic criteria for the disorders described above.

68 Depression

PREVALENCE OF DISORDER In the United States, lifetime prevalence of at least one depressive episode is estimated at 16.2% (Kessler et al., 2003). Approximately 16 million adults (6.9%) experienced at least one major depressive episode in 2012, of which 10.4 million adults (4.5%) experienced severe impairment (NIMH, 2014). Almost all adults (96.9%) with depression in the preceding 12 months reported related functional impairment such as an inability to work or be social (Kessler et al., 2003).

Depression often co-occurs with other neuropsychiatric or medical disorders. It is estimated that 72.1% of individuals with depression will experience a comorbid neuropsychiatric condition during their lifetime (Kessler et al., 2003), and that the rate of comorbidity between depression and medical conditions ranges from 10% to 40% (Goodnick & Hernandez, 2000). Further, co-occurring depression and medical illnesses appear to have a bidirectional relationship: depression increases the likelihood of medical illnesses and medical illnesses increase the likelihood of depression (Herring et al., 2010). Common chronic conditions such as diabetes and cardiovascular disease are key culprits; for example, diabetes doubles the odds of depression (Anderson et al., 2001). These high rates of comorbidity may be in part because depression is associated with health behaviors that negatively impact a range of medical disorders, including smoking, alcohol use, physical inactivity, and sleep disturbances (CDC, 2013). Depression is also associated with more medically unexplained symptoms (Herring et al, 2010).

ECONOMIC BURDEN OF DISORDER The annual economic burden of depression in the United States was estimated at $83.1 billion in 2000, an increase of about 7% over ten years from 1990 (adjusted for inflation). These increased costs coincided with a more than 50% increase in treatment (Greenberg et al., 2003). A review of cost-of-illness studies of depression consistently found increases in both direct and indirect costs, with additional direct costs of $1,000 to $2,500 per person with depression per year (Luppa et al., 2007). The highest direct costs are due to greater healthcare utilization beyond depression treatment (Donohue & Pincus, 2007; Simon et al., 2007). Contributing to these higher costs, depressed persons make more frequent healthcare visits for unexplained symptoms and less successfully manage their chronic conditions. The highest indirect costs are due to reduced workplace productivity, with estimates from $31 to $33.5 billion annually. However, these are considered underestimates that do not account for the losses due to absenteeism or disability leave (Donohue & Pincus, 2007; Greenberg et al., 2003; Stewart et al., 2003; Wang et al., 2003). Notably, treatment-resistant depression also increases overall societal costs, with estimates of an additional $29 to $48 billion annually for this subset of patients (Mrazek et al., 2014).

Importantly, many persons with depression either receive limited treatment (e.g., Stewart et al., 2003) or do respond to the treatment they receive (e.g., Mrazek et al., 2014). While it initially seemed that an increase in societal costs paralleled an increase in treatment, these increases appear to be driven more by general healthcare utilization and lost productivity. Moreover, it is believed that an increase in both frequency and quality of delivery of existing evidence-based

69 Depression treatment interventions would reduce overall costs (Wang et al., 2003). A review of workplace depression supported this, suggesting that productivity gains from successful treatment could exceed associated costs but that more data are needed (Simon et al., 2001a). Nonetheless, it is likely that an increase in treatment will ultimately have an economic net benefit for both employers and society at large.

CLINICALLY EFFECTIVE INTERVENTIONS Effective and acceptable pharmacotherapy and psychotherapy treatment options are already available for depression. Antidepressant medication is considered first-line treatment. Psychotherapy is recommended as an additional treatment. For mild to moderate depression, antidepressants and psychotherapy are considered similarly effective; thus, the recommendation is for patient preference to guide choice of treatment. For severe depression, antidepressants have been found to be more effective than psychotherapy.

Evidence-based psychotherapies for depression include Cognitive Behavioral Therapy (CBT), Interpersonal Therapy (IPT), Problem-Solving Therapy (PST), short-term Psychodynamic Therapy, Mindfulness-based Therapies, and Internet- or computer-based Cognitive Behavioral Therapy (Mitchell et al., 2013). At the time of writing, cost-effectiveness trials of Psychodynamic Therapy and Mindfulness-Based Therapies were not available, except for one trial on brief counseling that included both psychodynamic and cognitive behavioral approaches. Problem-Solving Therapy can only be found under Collaborative Care Management and telehealth interventions; however, standard Problem- Solving Therapy can be found in the Supplement on General Mental Health Problems.

In Cognitive Behavioral Therapy (CBT), a therapist works with a patient on a set of structured skills designed to identify and address maladaptive thought and behavior patterns that contribute to the development and maintenance of depression. In computerized Cognitive Behavioral Therapy, an automated interface walks patients through education and skills practice using Cognitive Behavioral Therapy protocols. Interpersonal Therapy (IPT) provides time-limited (typically 6-20 sessions) supportive psychotherapy focused on interpersonal issues to reduce psychological distress. Problem-Solving Therapy (PST) trains patients in problem-solving skills to help them address psychosocial challenges and interpersonal issues, and set and work toward goals.

In addition to these evidence-based psychotherapies, improvements in care delivery may improve the effectiveness of clinical management of depression. Quality improvement interventions for depression treatment in primary care have been found to be cost-effective, suggesting that better implementation of existing clinical treatments can improve outcomes in a cost-effective manner (Donohue & Pincus, 2007). In particular, Collaborative Care Management has been shown to improve depression outcomes (Gilbody et al., 2006). In this model, case managers help coordinate and monitor care and treatment progress for patients with depression, and support primary care physicians and mental health providers. These case managers may provide patient education, promote treatment adherence and self-care, work with the patient and providers to

70 Depression encourage changes to therapy when improvement is poor, and coordinate clinical care.

Lastly, multiple methods of self-care have evidence for effectiveness, including exercise (e.g. Trivedi et al., 2006), behavioral activation, in which patients are encouraged to identify and engage in healthful rewarding experiences (Dimidjian et al., 2006), and guided self-help modalities such as bibliotherapy. At the time of writing, cost-effectiveness trials for self-care methods were limited.

COST-EFFECTIVENESS OF INTERVENTIONS Cost-effectiveness for depression interventions has been measured in terms of various clinical outcomes including QALYs, number of depression-free or relapse-free days, number of improved or recovered patients, and incremental improvements on depression symptom measures (e.g., Beck Depression Inventory). In addition to the common benchmark willingness to pay threshold of $50,000 per QALY, a willingness to pay threshold of $10 to $20 per depression- free day (DFD) has been proposed and used in several studies (Unützer et al., 2003). No thresholds have been established for other outcomes at this time.

Prior reviews of cost-effectiveness for both pharmacological and psychological treatment of depression have not offered any strong recommendations for specific interventions due to insufficient and inconclusive data. A review limited to psychotherapy concluded cost-effectiveness was unclear (Schulberg et al., 2002). A review focused on treating depression in primary care reached similar conclusions about psychotherapy but noted that while psychotherapy cost significantly more than usual care it did not cost more than antidepressants (Bosmans et al., 2008). Similarly, a review of pharmacotherapy, psychotherapy, and care delivery concluded that while it was not possible to identify the most cost-effective strategy, cost-effectiveness had not yet been proven for psychological treatments: compared to usual care, psychological treatment was usually equally or more effective and equally or more costly, but compared to antidepressants, psychological treatment was usually less effective and more costly. Combining psychotherapy and pharmacotherapy may be the most promising avenue of additional research (Barrett et al., 2005). Finally, a review of Collaborative Care Management for depression in primary care found that cost- effectiveness ranged immensely and likely depended on willingness to pay thresholds (Grochtdreis et al., 2015).

Depression in Children and Adolescents A limited number of studies have assessed cost-effectiveness of behavioral interventions for depression in young people.

Prevention Interventions In adolescents who are considered at-risk for depression due to having at least one parent with depression, a Cognitive Behavioral Therapy (CBT)-based group prevention intervention was highly cost-effective compared to usual care after one year at $9,275 per QALY or $10 per depression-free day (DFD). These are well within standard willingness to pay thresholds (Lynch et al., 2005; Clarke et al., 2001). Meanwhile, a classroom-based CBT intervention (Resourceful

71 Depression

Adolescent Program-UK) provided to all students was no more cost-effective than the usual school health curriculum at reducing depressive symptoms (Short Moods and Feelings Questionnaire) for high-risk adolescents in the United Kingdom after a year (Stallard et al., 2013). It is worth noting this intervention did not target the high-risk adolescents directly.

Treatment Interventions Notably, Cognitive Behavioral Therapy (CBT) does not appear to be more cost- effective than medication for treating depression in young people based on short- term outcomes. As CBT attempts to teach skills that may prevent or shorten duration of later depression, studies of longer durations are warranted. A comparison of CBT, selective serotonin reuptake inhibitor (SSRI, a type of antidepressant medication), and both CBT and SSRI combined found that only options including the SSRI fluoxetine (either alone or in combination with CBT) were cost-effective after 12 weeks, and only fluoxetine alone was within the typical willingness to pay threshold (Domino et al., 2009; Domino et al., 2008; March et al., 2004).

For adolescents with persistent moderate to severe depression who have not responded to medication, the addition of CBT to on-going SSRI treatment demonstrated no clinical or cost advantages after 12 weeks (Goodyer et al., 2008; Byford et al., 2007). The addition of CBT along with switching medication was more clinically effective than switching medication alone after 24 weeks, but still outside the typical willingness to pay threshold. However, clinical effects were greater among certain subpopulations including youth with comorbid condition(s), with low levels of hopelessness, and without a history of abuse, and for them cost-effectiveness may approach reasonable levels (Lynch et al., 2011). Overall, CBT may be cost-effective for primary prevention in high-risk adolescents; however, it has not demonstrated clear cost-effectiveness compared to antidepressants for improving short-term outcomes in depressed children and adolescents. Cost-effectiveness trials that consider long-term effects and later adult course of depression in children and adolescents with depression are needed.

Table 1. Behavioral Interventions for Depression in Children and Adolescents Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Prevention Interventions Stallard et al. 3,177 Intervention: Short Moods PP: (2013) adolescents Resourceful and Feelings Healthcare (age 12-16 Adolescent Questionnaire Resourceful years) across 8 Programme, (SMFQ) for ICER (per Adolescent schools in UK. adapted for “high risk” QALY): Program-UK 1,006 in UK. participants Dominated (RAP-UK) to intervention, Classroom- (score ≥5 at reduce 1,044 in based baseline): All analyses depressive control #1, Cognitive I: 8.22 (6.45) but one found symptoms in 1,067 in Behavioral C1: 8.50 (5.88) RAP-UK to be

72 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness high-risk control #2. Therapy by C2: 6.81 (5.70) both less adolescents two trained (NS) effective and facilitators. more costly Typically nine d1: -.045 than control. In 50-60 minute d2: .232 that analysis, sessions. the ICER of Average cost £185,338 £41.96/child. exceeded typical willingness to Controls: pay thresholds. (1) Usual school health Willingness to curriculum pay threshold: plus support Approx. 5% from two probability facilitators. Resource Typically nine Adolescent 50-60 minute Program-UK sessions. more cost- Average cost effective than £34.45/child. usual school (2) Usual health school health curriculum curriculum. (with or without Measures: additional 12-month support of follow-up facilitators). Lynch et al. 94 adolescents Intervention: Center for PP: Societal (2005) & (age 13-18 Usual care Epidemiologic Clarke et al. years) in U.S. plus fifteen 1- al Studies– ICER (per (2001) who have a hour sessions Depression QALY):

parent with of group Scale (CES-D): $20009,275 Group depression Cognitive I: 15.1 (10.0) (95% CI, Cognitive and are at risk Behavioral C: 21.5 (13.6) -$12,148 to Behavioral for Therapy for $45,641) Therapy to depression. 45 depression d: .542 prevent in prevention. ICER (per depression in intervention, Average cost Hamilton DFD): at-risk 49 in control. $20001,632/adol Depression $200010 adolescents escent. Rating Scale (95% CI, -$13 (HAM-D): to $52) Control: I: 1.5 (2.7) Usual care. C: 2.6 (4.9) Willingness to pay threshold: Measures: d: .289 If value is

73 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness 12-month $20/DFD, follow-up Number of about 75% Depression- probability Free Days group (DFDs): Cognitive I: 301 (95% CI, Behavioral 279 to 320) Therapy more C: 248 (95% cost-effective CI, 214 to 283) than usual (p=.001) care.

Treatment Interventions Lynch et al. 334 patients Intervention: Number of PP: Societal (2011) (age 12-18 Switch to Depression- years) with different Free Days ICER (per Treatment of treatment- antidepressan (DFDs): QALY):

SSRI-Resistant resistant t medication I: 83.7 (56.7) $200678,948 Depression in depression plus 24 weeks C: 77.0 (52.9) (95% CI, Adolescents (moderate of Cognitive (p=.03) -$9,261 to (TORDIA) depressive Behavioral $677,448) combined severity Therapy. d: .122 Cognitive persists after Average cost

Behavioral SSRI $20061,633 more More effective Willingness to Therapy plus treatment for than control for subgroups pay threshold: medication ≥8 weeks) (p=.01). of youth with If value is compared to across 6 sites comorbid $100K/QALY, medication in U.S. 166 in Control: condition(s), 61% alone intervention, Switch to with low levels probability 168 in control. different of hopelessness, Cognitive antidepressan and without a Behavioral t medication. history of Therapy plus abuse. medication Measures: more cost- 24 weeks effective than medication alone.

ICER (per DFD):

$2006188 (95% CI, -$22 to $1,613)

Domino et al. 369 patients Interventions: Children’s PP: Societal (2008 & 2009) (age 12-18 (1) Selective Depression

74 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness & March et al. years) with serotonin Rating Scale ICER (per (2004) depression reuptake (CADS): QALY):

across 13 sites inhibitor I1: 36.30 (8.18) (1) $200323,737 Treatment of in U.S. 57% (SSRI; I2: 42.06 (9.18) (2)

Adolescents female. 94 in fluoxetine) I3: 33.79 (8.24) $20039,210,622 with intervention alone for 12 C: 41.77 (7.99) (3) $2003123,143 Depression #1, 89 in weeks. (4) $2003458,818 Study (TADS) intervention (2) Cognitive d1: .677 comparing #2, 92 in Behavioral d2: -.034 Willingness to Cognitive intervention Therapy d3: .983 pay threshold: Behavioral #3, 94 in (CBT) alone d4 (I3 vs. I1): If value is Therapy, control. for 12 weeks. .306 $200K/QALY, selective (3) SSRI plus both SSRI serotonin CBT for 12 alone and reuptake weeks. SSRI plus inhibitor, and Cognitive both Control: Behavioral combined Placebo for 12 Therapy are weeks. ≥95% probability Measures: more cost- 12 weeks effective than placebo. Goodyer et al. 188 adolescent Intervention: HoNOSCA PP: (2008) & patients (age Routine (Health of the Healthcare Byford et al. 11-17 years) clinical care Nation and Social (2007) with and SSRI plus Outcome Services persistent weekly Scale for Adolescent moderate to Cognitive Children and ICER (per Depression severe Behavioral Adolescents): QALY): Antidepressan depression in Therapy for I: 15.39 (8.58) Dominated t and UK. 96 in 12 weeks C: 14.52 (8.26) Psychotherap intervention, followed by (NS) Willingness to y Trial 92 in control. biweekly pay threshold: (ADAPT) for maintenance d: .103 Max. 2-4% persistent sessions for 12 probability depression weeks and No difference addition of final session between Cognitive at 28 weeks. intervention Behavioral Cost estimate and control for Therapy more £1273/child. any measure. cost-effective than routine Control: clinical care Routine and SSRI clinical care alone. and SSRI only.

75 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Measures: 12-week follow-up

Depression in Adults The cost-effectiveness of depression treatment in adults is comparatively well studied, with almost 30 published RCTs examining behavioral interventions.

The most commonly studied in-person psychotherapies for depression are Interpersonal Therapy (IPT) and Cognitive Behavioral Therapy (CBT). There are, as well, some studies of non-directive or generic therapy, short-term counseling, or supportive care. Additionally, some programs focus on improving the quality of depression treatments in primary care. Overall, these interventions are compared against usual care, against each other, and/or against antidepressant medication.

Interpersonal Therapy (IPT) It is unclear whether Interpersonal Therapy (IPT) or antidepressant medication is more cost-effective for Major Depression or Dysthymic Disorder (persistent mild depression for at least two years).

For Major Depression in primary care, both IPT and medication (nortriptyline hydrochloride) were more cost-effective than usual care. ICERs indicated incremental costs were lower for medication in terms of both QALYs and depression-free days (DFDs). Overall, medication was slightly more effective and slightly less costly than IPT, suggesting it may be the more cost-effective option. Notably, if IPT were at 80% of its direct costs, it would also fall within a willingness to pay threshold of $20,000 per QALY (Lave et al., 1998).

Meanwhile, a Canadian study of Dysthymic Disorder (with or without Major Depression) found comparable cost-effectiveness for IPT alone, selective serotonin reuptake inhibitor (SSRI; an antidepressant medication) alone, and IPT plus SSRI. All three treatments cost more than CN$500 per incremental improvement on a depression scale (Montgomery Asberg Depression Rating Scale) after two years (Browne et al., 2002). Whether any of the three options would be considered cost-effective depends on the willingness to pay threshold. Overall, IPT and antidepressants may be similarly cost-effective, but there is insufficient evidence to recommend IPT as the more cost-effective option.

Table 2. Interpersonal Therapy (IPT) for Depression in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Browne et al. 586 adults Interventions: Montgomery PP: (2002) (age 18-74 (1) Selective Asberg Healthcare years) with serotonin Depression and Social Interpersonal Dysthymic reuptake Rating Scale Services

76 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Therapy Disorder inhibitor (MADRS) at 6 and/or (with or (SSRI; months: ICER (per 1- selective without Major sertraline) I1: 14.3 (9.8) point serotonin Depression) in alone. I2: 16.8 (10.6) improvement reuptake Canada. 179 (2) I3: 15.0 (10.4) in MADRS): inhibitor for in Interpersonal I1: CN$595.91 Dysthymic intervention Therapy (IPT) d1 (I3 vs. I1): I2: CN$554.61 Disorder #1, 190 in alone for 10 -.069 I3: CN$543.09 intervention sessions. d2 (I3 vs. I2): #2, 156 in (3) SSRI plus .171 intervention IPT combined. d3 (I2 vs. I1): #3. -.245 Measures: 2-year follow- up Lave et al. 276 patients Interventions: Depression- PP: (1998) with Major (1) Free Days Healthcare Depression in Nortriptyline (DFDs)*: Interpersonal primary care. hydrochloride I1: 220-243 ICER (per Therapy vs. 91 in with weekly/ I2: 187-234 QALY): medication for intervention biweekly C: 148-185 I1: $10,181- depression in #1, 93 in visits until (p≤.01) $17,112 primary care intervention blood level I2: $26,130- #2, 92 in reaches *Range based $37,533 control. therapeutic on two different state and measures. symptoms Lower bound improve. based on Beck ICER (per (2) Depression DFD): Interpersonal Inventory I1: $11.44- Therapy for (BDI) and $14.79 approx. 16 upper bound I2: $29.36- weekly acute- based on $32.44 phase sessions Hamilton then 4 Rating Scale- ICERs for monthly Depression Interpersonal continuation (HRS-D). Therapy sessions. exceeded those for Control: nortriptyline Usual care. hydrochloride, which was Measures: slightly better 12 months in outcomes and costs.

77 Depression

Cognitive-Behavioral Therapy (CBT) Cognitive Behavioral Therapy (CBT) and antidepressant medication demonstrated similar cost-effectiveness in the populations studied. There was a surprising lack of cost-effectiveness studies in the general population given the common usage of CBT.

Treatment Interventions For predominantly low-income minority women with Major Depression, both CBT (choice of group or individual delivery) and selective serotonin reuptake inhibitor (SSRI; a type of antidepressant medication) significantly reduced the number of depression-free days (DFDs) compared to referral to community resources after 12 months. CBT cost $17,624 per QALY and SSRI cost $30,023 per QALY, both within standard willingness to pay thresholds. Nevertheless, the wide 95% confidence interval ($13,617 to $90,911) indicated that cost- effectiveness varied, with CBT more cost-effective for some patients but SSRI more cost-effective for others (Revicki et al., 2005; Miranda et al., 2003).

In treatment-resistant patients (i.e. did not respond to antidepressants) in the United Kingdom, the addition of CBT was cost-effective at £14,911 per QALY after twelve months (Hollinghurst et al., 2014; Wiles et al., 2013). This differed from short-term outcomes among adolescents with persistent or treatment- resistant depression, where the addition of CBT was not cost-effective alongside either the same medication or a switch to a new one (Goodyer et al., 2008; Byford et al., 2007; Lynch et al., 2011).

Interestingly, cost-effectiveness of CBT did not differ from non-directive therapy in one study (Bower et al., 2000; Ward et al., 2000), as discussed later. However, telehealth CBT via phone or Internet did demonstrate cost-effectiveness (Warmerdam et al., 2010; Simon et al., 2009; Hollinghurst et al., 2010; Gerhards et al., 2010; McCrone et al., 2004; Proudfoot et al., 2004), also as discussed later.

Secondary Prevention Interventions No studies were available for preventing the initial onset of depression, but one study in the United Kingdom compared psychotherapy and medication for relapse prevention in patients with partially remitted chronic depression. Adding Cognitive Therapy to antidepressants and clinical management cost £4,328 more per each additional relapse prevented compared to antidepressants and clinical management alone. Cognitive Therapy was 60 to 80% likely to be cost-effective if prevention of a relapse was valued at £6,000 to £8,500 after 17 months (Scott et al., 2003; Paykel et al., 1999). With no standard willingness to pay threshold for this metric, the cost-effectiveness will depend on the decision- maker.

78 Depression

Table 3. Cognitive-Behavioral Therapy (CBT) for Depression in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Treatment Interventions Hollinghurst 395 patients Intervention: Beck PP: et al. (2014) & (age 18-75 Usual care Depression Healthcare Wiles et al. years) with plus Inventory and Social (2013) depression in Cognitive (BDI): Services primary care Behavioral I: 17.0 (14.0) Adjunctive who have not Therapy for C: 21.7 (12.9) ICER (per Cognitive responded to 12-18 hour- (p<.001) QALY):

Behavioral antidepressan long sessions. £201014,911 Therapy for t treatment in Average cost d: .349 treatment- UK. 72% £910/patient. Willingness to resistant female. 197 in pay threshold: depression intervention, Control: If value is (CoBalT Trial) 198 in control. Usual care. £20K/QALY, 74% Measures: probability 12 months Cognitive Behavioral Therapy more cost-effective than usual care, and if value is £30K, 91% probability more cost- effective. Revicki et al. 267 women Interventions: Hamilton PP: (2005) & with Major (1) Depression Healthcare Miranda et al. Depression, Pharmacother Rating Score (2003) predominantl apy (HDRS) at 6 ICER (per y low-income (paroxetine or months: QALY): Treating minority bupropion) I1: 5.2 (95% I1: $30,023 Major women. 88 in for up to 6 CI, 3.0 to 7.3) (95% CI, Depression in intervention months. I2: 7.2 (95% $13,617 to low-income #1, 90 in (2) Cognitive CI, 5.0 to 9.3) $90,911) women intervention Behavioral C: 10.1 (95% I2: $17,624 #2, 89 in Therapy for 8 CI, 8.0 to 12.3) (95% CI, control. weekly $14,590 to individual or d1: .667 $2,836,158) group d2: .398 sessions. Option to Depression- extend for an Free Days additional 8 (DFDs):

79 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness weeks. I1: 258 (95% CI, 236 to 280) Control I2: 251 (95% Brief CI, 230 to 273) education (p=.05) plus referral C: 225 (95% to community CI, 206 to 244) providers. d1: .366 Measures: d2: .247 12-month follow- up Secondary Prevention Interventions Scott et al. 158 Intervention: Hamilton PP: (2003) & psychiatric Antidepressan Depression Healthcare Paykel et al. patients (age ts and clinical Rating Score (1999) 21-65 years) management (HDRS): ICER (per with partially plus I: 8.58 relapse Cognitive remitted Cognitive C: 9.40 prevented): Therapy for Major Therapy for (NS) £4,328 relapse Depression in 16 sessions prevention in UK. 80 in over 20 weeks d: NC Willingness to chronic intervention, and 2 booster pay threshold: depression 78 in control. sessions. Beck If value is Average cost Depression £6,000/additi £779 more Inventory onal relapse than control. (BDI): prevented, I: 13.46 >60% Control: C: 16.06 probability Antidepressan (NS) addition of ts and clinical Cognitive management d: NC Therapy more alone. cost-effective Percent than Measures: Cumulative antidepressan 17 months Relapse Rates: ts alone, and if I: 29% value is C: 47% £8,500, >80% (p=.02) probability more cost- effective.

Generic Therapy, Counseling, or Supportive Care Non-directive or generic therapy, short-term counseling, and supportive care in primary care settings have not demonstrated cost-effectiveness compared to

80 Depression standard treatments of Cognitive Behavioral Therapy (CBT) or antidepressant medication.

Non-directive therapy and CBT had no significant cost differences with each other or usual care after four months or one year for patients with either depression or mixed anxiety and depression; moreover, both therapies were more clinically effective than usual care at four months. Although these differences were not sustained after one year, they suggest the short-term cost- effectiveness of both therapies (Bower et al., 2000; Ward et al., 2000). Similarly, a study in the United Kingdom found that short-term counseling in primary care using either psychodynamic or cognitive behavioral approaches had no clinical or cost differences compared to usual care after a year for patients with chronic depression with or without anxiety (Simpson et al., 2003; Simpson et al., 2000).

Compared to antidepressants, generic therapy was slightly more expensive and slightly less effective, but was dominant for a small proportion of patients. Antidepressants were dominant for a much larger proportion, with the probability of cost-effectiveness increasing with the willingness to pay threshold (greater than 90% likelihood if value were greater than £2,000 per additional patient with positive outcome). For the remainder, cost-effectiveness will depend on how much the decision-maker is willing to pay (Miller et al, 2003; Chilvers et al., 2001). Meanwhile, the addition of selective serotonin reuptake inhibitor (SSRI) to supportive care compared to supportive care alone for depressed patients with somatic symptoms in the United Kingdom was cost- effective at £14,854 per QALY after 26 weeks. In this study, supportive care was not compared to other types of counseling or usual care (Kendrick et al., 2009).

Table 4. Generic Therapy, Counseling, or Supportive Care for Depression in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Kendrick et al. 220 patients Intervention: Hamilton PP: Healthcare (2009) with Supportive care Depression depression plus selective Rating Scale ICER (per Selective with somatic serotonin (HDRS): QALY): £14,854 serotonin symptoms in reuptake I: 7.92 (5.67) reuptake primary care inhibitor (SSRI) C: 9.73 Willingness to inhibitor plus in UK. 112 in treatment. (5.57) pay threshold: supportive care intervention, If value is vs. supportive 108 in Control: d: .322 £20K/QALY, care alone for control. Supportive care 65% probabil- depression alone. ity intervention with somatic more cost- symptoms Measures: effective than 26 weeks control, and if value is £30K, 75% probability more cost- effective.

81 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Simpson et al. 115 patients Intervention: Percent PP: Healthcare (2003) & with chronic Routine care Cases (≥14 Simpson et al. depression plus referral to on Beck Total Service (2000) with or practice Depression Costs:

without counselor with Inventory): I: £19981,046 Short-term anxiety in either cognitive I: 48% C: £19981,074 counseling for primary care behavioral or C: 64% (NS) chronic in UK. 60 in psychodynamic (p=.02) depression intervention, approach. Cost No significant with or 55 in control. £1998486/ No differences in without person. significant costs. Additional anxiety in differences in cost of primary care Control: continuous counseling not Routine care. score, only in offset with

Cost £1998371/ number of reduced costs for person. cases. other services.

Measures: 12 months Miller et al. 207 patients Interventions: Beck PP: Healthcare (2003) & with mild to (1) Generic Depression Chilvers et al. moderate psychological Inventory Total (2001) depression in therapy (BDI): Depression- primary care (counseling) I1: 13.2 Related Service Counseling vs. in UK. 65 with six 50- (11.3) Costs: antidepressants randomized minute weekly I2: 12.8 Randomized for mild to into sessions. (10.7) patients moderate treatment, (2) (NS) I1: £343.64 depression 142 selected Antidepressant (61.87) preferred medications. d: .036 I2: £301.63 treatment. (37.72) Overall, 127 Measures: in 12 months Patient intervention preference #1 (31 I1: £335.63 randomized), (24.86) 80 in I2: £263.41 intervention (33.84) #2 (34 randomized). Willingness to pay threshold: If no value per patient with improved outcome, 45% probability

82 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness antidepressants more cost- effective than counseling. If value is >£2K, >90% probability antidepressants more cost effective. Bower et al. 197 patients Interventions: Beck PP: Societal (2000) & Ward with (1) Cognitive Depression et al. (2000) depression Behavioral Inventory Total Costs: Cognitive or mixed Therapy for 6- (BDI): At 4 months Behavioral anxiety and 12 sessions. At 4 months I1: $501.6 Therapy and depression in (2) Non- I1: 12.7 (9.5) (715.3) non-directive UK. 75% directive I2: 11.5 (7.7) I2: $701.9 therapy for women. 63 in therapy for 6- C: 17.2 (1228.4) patients with intervention 12 sessions. (11.9) C: $627.7 depression or #1, 67 in (1,359.8) mixed anxiety intervention Control d1: .421 and depression #2, 67 in Usual care. d2: .582 At 12 months in primary care control. I1: $1,060.5 Measures: At 12 (1,471.1) 4 months & 12 months I2: $1,398.6 months I1: 9.3 (8.8) (2,474.1) I2: 11.1 (9.3) C: $1,217.5 C: 10.2 (8.5) (2,013)

d1: .104 At both 4 and 12 d2: -.101 months, no significant Both differences interventions between groups more for any cost effective than measurements. usual care at 4 months, but no differences at 12 months.

Collaborative Care Management and Improved Quality of Care Collaborative Care Management (CCM) and other quality improvement programs for depression in primary care were all cost-effective compared to

83 Depression usual care, including for different subpopulations of patients. No trials compared CCM to other types of interventions.

For patients with depression starting antidepressants in primary care, adding a Care Management program of telephone follow-up, treatment recommendations, and practice support to automated, algorithm-based Feedback for providers was more clinically effective than either Feedback alone or usual care. There were no differences in healthcare utilization or total healthcare costs after six months. Specifically, the Care Management program had a significantly higher probability of leading to treatment response (at least 50% decrease in depression scores) and a lower probability of persistent depression. These improvements, plus lack of cost differences, and low costs of implementation ($80 per patient) suggest cost-effectiveness for Care Management but not for Feedback (Simon et al., 2000).

A Collaborative Care Management program with care managers for psychoeducation, medication management, behavioral activation, and relapse prevention for patients with depression in the United Kingdom was more clinically effective than usual care. The CCM program led to higher rates of response and recovery and only cost £14,248 per QALY, within the standard willingness to pay threshold. The authors predicted that CCM would dominate as cost-saving if analysis took a broader perspective that included the costs of informal care (Green et al., 2014; Richards et al., 2013).

A similar Collaborative Care Management program including brief Cognitive Behavioral Therapy (CBT) plus enhanced patient education and medication management was compared to usual care for patients with both major and minor depression (i.e. at least two but less than five depressive symptoms) across two trials. Collaborative Care Management led to significantly greater clinical improvement for Major Depression but not minor depression, though it had the potential to be cost-effective for both disorders after four months depending on the willingness to pay threshold. It cost $940-$1,592 per successfully treated individual with Major Depression, but had more varied results for minor depression: it was cost-saving at $8,190 per successfully treated individual in one trial and cost $3,741 per successfully treated individual in the other (Von Korff et al., 1998; Katon et al., 1996; Katon et al., 1995).

For patients with depression who were high utilizers of general medical care for at least two years, a Depression Management program of patient education, phone care management, antidepressants (if appropriate), and optional psychiatric consultation cost $51.84 per additional depression-free day (DFD) after a year, which was not within the typical willingness to pay threshold for DFDs. However, the authors estimated it to be just within the typical threshold at $49,500 per QALY (Simon et al., 2001c; Katzelnick et al., 2000). For veterans with depression, a Collaborative Care Management program with a mental health team to provide a treatment plan and telephone support to encourage adherence and modifications was cost-effective at $21,444 to $42,838 per QALY or $24 to $33 per additional DFD after nine months (Liu et al., 2003; Hendrick et al., 2003).

84 Depression

Lastly, a stepped Collaborative Care Management program, where the intensity of services is increased stepwise, if and when a patient does not show improvement at a lower intensity of care, cost $35 per additional DFD, with a greater than 98% likelihood of being cost-effective for patients with persistent depression after six months (Simon et al., 2001b). A similar stepped Collaborative Care Management program for patients with persistent depression assessed whether these short-term effects of improved medication adherence and decreased depression symptoms persisted after 28 months. The stepped CCM program sustained improvements in patients with moderate-severity symptoms but not patients with high-severity symptoms. With no differences in total healthcare costs, the stepped CCM program remained cost-effective at this longer time interval (Katon et al., 2002). Thus, across major depression, minor depression, persistent depression, high utilizers of medical care, and veterans, Collaborative Care Management in primary care, including stepped versions, demonstrated cost-effectiveness for improving depression outcomes up to two years later.

Additionally, an intervention focused on training nurses to improve quality of care also included care management similar to that provided in Collaborative Care Management programs. For patients beginning a new depression episode, nurses providing enhanced care through regularly scheduled care maintenance was more cost-effective than usual care at $9,592 to $14,306 per QALY over two years. Interestingly, the clinical improvements were even greater in the second year than the first one (Rost et al., 2005).

These findings were corroborated by a large-scale quality improvement program for both main types of depression treatment (medication or therapy) over two years. For medication quality improvement, nurse specialists were trained to support medication adherence through visits and phone calls. For therapy quality improvement, therapists were trained to provide individual and/or group Cognitive Behavioral Therapy. Both programs were more cost-effective than enhanced usual care at $15,331 to $36,467 per QALY for medication quality improvement and $9,478 to $21,478 for therapy quality improvement. However, further analyses revealed that cost-effectiveness was much better for persons with subthreshold depression (i.e. depressive symptoms but no depressive disorder) than for persons with depressive disorders ($2,028 versus $53,716 per QALY), with the latter exceeding the standard willingness to pay threshold of $50,000 (Wells et al., 2007; Schoenbaum et al., 2001).

Implementing these types of programs always cost more than usual care, making it all the more noteworthy that they all demonstrate cost-effectiveness.

85 Depression

Table 5. Collaborative Care Management and Improved Quality of Care for Depression in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Green et al. 581 adults Intervention: Patient Health PP: (2014) & with Usual care Questionnaire Healthcare Richards et al. depression in plus -9 (PHQ-9): and Social (2013) primary care Collaborative I: 10.0 (7.1) Services in UK. 276 in Care C: 11.7 (6.8) Collaborative intervention, Management (p=.04) ICER (per Care 305 to control. with care QALY):

Management managers for d: .245 £201114,248 for depression education in primary about Generalized Willingness to care (CADET) depression, Anxiety pay threshold: medication Disorder-7 If value is management, (GAD-7): £20K/QALY, behavioral I: 7.7 (6.2) 58% activation, C: 9.1 (6.2) probability and relapse (p=.06) Collaborative prevention for Care is more 6-12 contacts d: .226 cost-effective over 14 weeks than usual (1 30-40 Percent care. If value minute in- Response is £30K, 65% person (≥50% probability meeting, then reduction on more cost- 15-20 minute PHQ-9): effective. phone calls). I: 49% Mean cost of C: 36% £272.50/partic ipant. Percent Recovery (≤9 Control: on PHQ-9): Usual care. I: 56% C: 41% Measures: 12-month follow-up Wells et al. 1,356 patients Intervention: PP: Societal (2007) & across 46 (1) Medication Incremental Schoenbaum primary care quality Improvement ICER (per et al. (2001) clinics in U.S. improvement in Days of QALY):

746 with 12- with nurse Depression I1: $199815,331- Quality month specialists Burden: $199836,467 improvement depressive supporting Depressive I2: $19989,478- programs for disorder, 502 adherence via disorder $199821,478 patients with with monthly visits I1: .-24 (95%

86 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness depressive depressive or calls for 6- CI, -67 to 19) Depressive disorders or symptoms but 12 months. (NS) disorder subthreshold no disorder. Average cost I2: -64 (95% I1+I2: $53,716 depression Randomized $86/patient. CI, by practice. (2) Therapy -106 to -21) Subthreshold 424 in quality (p<.01) depression intervention improvement I1+I2: $2,028 #1, 489 in with d: NC intervention therapists #2, 443 in trained to Subthreshold control. provide depression individual I1: -.37 (95% and/or group CI, -87 to 14) Cognitive (NS) Behavioral I2: -25 (95% Therapy. CI, -70 to 21) Average cost (NS) $79/patient. d: NC Control: Enhanced usual care.

Measures: 24 months Rost et al. 211 patients Intervention: Depression- PP: Societal (2005) beginning Enhanced care Free Days new with practice (DFDs): ICER (per Enhancing depression nurses I: 647.6 QALY): primary care treatment providing C: 588.2 $20009,592- depression across 12 regularly (p<.01) $200014,306 management primary care scheduled practices in care d: NC 100% U.S. 84.4% management. probability of female. Clinical benefit being less than Control: improves with $20,000 per Usual care. time (higher in QALY. second year Measures: than first). 24 months

Liu et al. 310 veterans Intervention: Mean Change PP: (2003) & in U.S. Collaborative in Symptom Healthcare Hendrick et Department of Care Checklist al. (2003) Veteran Management Depression ICER (per Collaborative Affairs (VA) program with Scale (SCL- QALY):

87 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Care primary care mental health 20): $21,444- Management clinic with team I: -.41 (SE .05) $42,838 for depression Major treatment C: -.25 (SE .06) in veteran Depression or plan, phone ICER (per population Dysthymia. management, d: .218 DFD): 146 in and $24-$33 intervention, monitoring Depression- 164 in control. and Free Days 96.6% modification. (DFDs): probability that Average I: 112.7 (81.1) intervention additional C: 107.3 (75.6) increases both treatment (NS) effectiveness costs $237/ and costliness. patient. d: .069 3.4% probability Control: traditional Traditional consult-liaison consult-liaison could be care. dominant.

Measures: 9 months Katon et al. 187 patients Intervention: Symptom PP: (2002) with Stepped Checklist – Healthcare persistent Collaborative Depression Long-term depression 2 Care Score: Total Annual effects of months after Management Moderate- Healthcare stepped initiating targetting severity Costs: Collaborative antidepressan patient, I: .88 (.52) I: $9,192 (95% Care ts in primary physician, and C: 1.23 (.62) CI, 7,504 to Management care clinics. 95 process of (p=.004) 10,800) for persistent in care with C: $9,799 (95% depression intervention, educational d: .593 CI, 7,763 to 92 in control. book and 11,834) videotape, 2 High-severity (NS) psychiatrist I: 1.16 (.85) sessions, C: 1.19 (.72) regular (NS) physician sessions, and d: .038 brief follow- up calls. Sheehan Disability Control: Scale: Usual care. Moderate- severity

88 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Measures: I: 3.09 (2.30) 28 months C: 3.58 (2.37) (NS)

d: .210

High-severity I: 3.41 (2.61) C: 3.20 (2.66) (NS) d: .080 Simon et al. 219 patients Intervention: Depression- PP: (2001b) with Stepped Free Days Healthcare persistent Collaborative (DFDs): Stepped depression in Care I: 87.7 (95% ICER (per Collaborative primary care Management CI, 76.6 to DFD): Care in U.S. 74% with patient 96.7) $35.05 (95% Management female. 110 in education, C: 70.9 (95% CI, -51.73 to for persistent intervention, consulting CI, 60.8 to 387.54) depression 109 in control. psychiatrist, 81.3) monitoring of (p=.02) >98% visits, and probability medication d: NC stepped adherence. Collaborative Control: Care Usual care. Management more cost- Measures: effective than 6 months usual care. Simon et al. 369 patients Intervention: Hamilton PP: (2001c) & with current Depression Depression Healthcare Katzelnick et depressive Management Rating Scale al. (2000) disorders not program with (HDRS): ICER (per in active patient I: 9.9 QALY): Depression M treatment, education, C: 13.6 $49,500 anagement for who are high phone care (p<.001) high utilizers utilizers of management, ICER (per of general me general antidepressan d: NC DFD): dical care medical ts (if $51.84 services in appropriate), Depression- U.S. 202 in and optional Free Days intervention, psychiatric (DFDs): 167 in control. consultation. I: 229.3 Average cost C: 181.9 $135/patient d: NC

89 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Control: Usual care.

Measures: 12 months Simon et al. 575 patients Interventions: Average PP: (2000) with (1) Feedback Outpatient Healthcare depression only including Visits: starting algorithm- I1: 4.40 (3.79) Total antidepressan based I2: 4.62 (3.44) Healthcare t treatment in recommendati C: 4.61 (4.58) Costs*: primary care ons to doctors. I1: $1,673 clinics. 207 in (2) Feedback Symptom (3,072) intervention plus care Checklist – I2: $1,729 #1, 188 in management Depression (3379) intervention including Score: C: $1,645 #2, 180 in phone follow- I1: not (2,646) control. up, treatment included (NS) recommendati I2: .83 *Single outlier ons, and (p=.008) removed from practice C: .98 care support by a management, care manager otherwise for 16 weeks. $2,327 (8,803). Cost $80/patient.

Control: Usual care

Measures 6 months Von Korff et 332 patients Intervention: >50% PP: al. (1998), with major or Collaborative Improvement Healthcare Katon et al. minor Care on Symptom (1996) & depression in Management Checklist ICER (per Katon et al. primary care with brief (SCL) successfully (1995) from two Cognitive Depression treated RCTs. 195 in Behavioral Scale: individual): Collaborative trial #1, 137 in Therapy, Trial #1 Trial #1 Care trial #2. 169 in enhanced Major Major Management intervention, patient depression depression for major and 163 in control. education, I: 74.4% $1,592 minor and C: 43.8% depression medication (p<.01) Minor across two management. depression

90 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness studies Trial #1 with Minor $8,190 psychiatrist depression consulting I: 60.0% Trial #2 services, trial C: 67.9% Major #2 with (NS) depression psychologist $940 providing Trial #2 brief therapy. Major Minor depression depression Control: I: 70.4% $3,741 Usual care. C: 42.3% (p=.04) Measures: 4-month Minor follow-up depression I: 66.7% C: 52.8% (NS)

Brief Therapy-Based Treatments All studies of brief or time-limited therapies are from the Netherlands and have the potential to be cost-effective, possibly due to the decreased costs of implementation. Importantly, cost-effectiveness must be measured at similar time intervals as other interventions to be able to compare duration of costs and effects.

Prevention Interventions To prevent onset of Major Depression in high-risk patients with subthreshold depression (i.e. 2-4 depressive symptoms without meeting diagnostic criteria) in primary care, Minimal Contact Psychotherapy with a self-help manual for mood management and guided by a few short phone calls with a prevention worker was cost-saving compared to usual care at €288.75 saved per avoided depression after one year. There was a 70% likelihood of being cost-effective even if no value were ascribed to an avoided depression (Smit et al., 2006; Willemse et al., 2004).

Treatment Interventions Brief Therapy, which is considered a formalized stepped care approach (i.e. intensity is only increased if/when the patient does not show improvement), was not cost-effective compared to stepped care Cognitive Behavioral Therapy (CBT) or usual care for patients with depression and/or anxiety after 18 months (van Roijen et al., 2006). However, Cognitive Self-Therapy (CST), where patients were trained on how to participate in and manage peer-based CST groups, had the potential to be cost-effective for patients with depression and/or anxiety after 18 months. While it did not demonstrate any significant clinical benefits over usual care (10-20 contacts with a psychologist, psychiatric nurse or social worker), it cost $156 per incremental improvement on a health measure (Symptom

91 Depression

Checklist-90), which may be cost-effective depending on the willingness to pay threshold (Stant et al., 2008; den Boer et al., 2007).

Table 6. Brief Therapy-Based Treatments for Depression in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Prevention Interventions Smit et al. 216 primary Intervention: Incidence Rate PP: Societal (2006) & care patients Usual care of Depression: Willemse et (age 18-65 plus Minimal I: 11.9% ICER (per al., 2004 years) with Contact C: 18.3% avoided subthreshol Psychotherap (p=0.04) depression): Minimal d depression y for -€288.75 Contact (2-4 depression. Center for Psychotherap depressive Self-help Epidemiologica Willingness to y in primary symptoms) manual with l Studies pay threshold: care for in the instructions Depression If no value per preventing Netherlands on mood (CES-D): avoided depression . 107 in management, I: 9.4 (7.4) depression, intervention, guided by 6 C: 11.1 (9.4) 70% probabil- 109 in short phone (p=.032) ity Minimal control. calls with a Contact prevention d: .202 Psychotherap worker. y more cost- effective than Control: usual care. If Usual care. value is €20K, 80% probabil- Measures: ity more cost- 1 year effective, and if value is €30K, 83% probability more cost- effective. Treatment Interventions Stant et al. 151 patients Intervention: Symptom PP: Societal (2008) & den with Major Cognitive Self- Checklist 90 Boer et al. Depression Therapy with (SCL-90): ICER (per 1- (2007) (MDD) or peers and I: 178.5 (66.9) point Generalized trained to C: 200.3 (75.6) improvement Cognitive Anxiety manage (NS) in SCL-90):

Self-Therapy Disorder meetings, then -$2003156 for depression (GAD) in the participating d: .306 and anxiety Netherlands. in self-therapy Willingness to 52% meetings led Depression pay threshold: comorbid. 75 by trained subscale If value is (91% MDD, peers. I: 2.25 (.96) $108/1-point

92 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness 9% GAD) in C: 2.45 (1.01) improvement intervention, Control: (NS) in SCL-90, 76 (97% Treatment as d: .203 83% MDD, 3% usual (10–20 probability GAD) in contacts with Beck Cognitive control. psychologist, Depression Self-Therapy psychiatric Inventory more cost- nurse or social (BDI): effective than worker). I: 15.4 (11.2) treatment as C: 18.6 (12.9) usual. Measures: (NS) 18 months d: .266 van Roijen et 646 patients Intervention: Utility Scores: PP: Societal al. (2006) with Brief Therapy, I: .71 (SE .04) depression which is C1: .65 (SE .04) ICER (per Brief Therapy and/or considered a C2: .69 (SE .04) QALY): for depression anxiety across stepped care Direct medical and anxiety 7 mental approach, d1: .011 costs

healthcare focuses mainly d2: .003 €2002262,857 institutes in on the present the and Total medical Netherlands. emphasizes costs

47% mood abilities rather €2002222,956 disorder, 12% than anxiety disabilities. ICER based on disorder, 41% control #1, comorbid for Controls: which always both. 187 in (1) Stepped had lower costs intervention, care Cognitive and better 214 in control Behavioral outcomes than #1, 245 in Therapy (CBT) control #2. control #2. for maximum of 15 sessions. Willingness to (2) Usual care. pay threshold: CBT is most Measures: cost-effective. 18-month However, the follow-up preference for CBT becomes less strong as the threshold increases.

Telehealth-Based Therapy New technologies allow distance-based treatments via the telephone or Internet. Some include virtual access to a therapist and others are completely self-driven,

93 Depression but in all cases they are more cost-effective than usual care. Comparisons to standard in-person therapy are pending. The majority of telehealth interventions tested were Cognitive Behavioral Therapy (CBT)-based, with only one that was Problem-Solving Therapy (PST)-based.

After two years, telephone care management was not more cost-effective than usual care for patients with significant depressive symptoms starting antidepressant treatment in primary care. However, telephone care management plus telephone-delivered CBT was more cost-effective than usual care if an additional depression-free day (DFD) were valued at $9 or more, which falls within the standard willingness to pay threshold (Simon et al., 2009).

Meanwhile, both Internet-based CBT and PST were more cost-effective than a waiting list control for adults with clinically significant depressive symptoms in the Netherlands, with the PST version at almost half both the costs and cost- effectiveness of the CBT version after a year (€11,523 per QALY versus €22,609 per QALY;Warmerdam et al., 2010; Warmerdam et al., 2008). Similarly, therapist- delivered Internet-based CBT was more cost-effective than treatment as usual after eight months at £17,173 per QALY (Hollinghurst et al., 2010).

Two computerized versions of CBT without professional support were also tested: “Colour Your Life” (Netherlands) and “Beating the Blues” (United Kingdom). “Colour Your Life” with or without usual care and usual care alone were similarly cost-effective after a year but varied depending on the willingness to pay threshold: at no to low thresholds, computerized CBT alone was more likely to be cost-effective, but at a threshold of €80,000 per QALY, computerized CBT alone and usual care alone were equally likely to be cost-effective (Gerhards et al., 2010). Meanwhile, “Beating the Blues” for patients with depression, anxiety, or mixed depression and anxiety had a 99% likelihood of being more cost-effective than usual care at a willingness to pay threshold of £15,000 per QALY after six months (McCrone et al., 2004; Proudfoot et al., 2004).

Table 7. Telehealth-Based Therapy for Depression in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Warmerdam 147 adults with Interventions Center for PP: Societal et al (2010 & clinically : Epidemiologic 2008) significant (1) Internet- al Studies ICER (per depressive based Depression QALY): Internet- symptoms in Cognitive (CES-D) scale: I1: €22,609 based the Behavioral I1: 17.9 (11.7) I2: €11,523 treatment for Netherlands. Therapy I2: 18.4 (12.1) adults with 71% female. 45 (CBT) with C: 25.8 (10.4) Willingness to depressive in intervention weekly (p<.001) pay threshold: symptoms #1, 40 in sessions for 8 If value is intervention weeks plus a d1: .715 €30K/QALY, #2, 62 in booster d2: .658 52% probabil- control. session after ity CBT and

94 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness 12 weeks. 61% (2) Internet- probability based Prob- PST more lem-Solving cost-effective Therapy than waiting (PST) with list. If value is weekly €10K/clinicall sessions for 5 y significant weeks. change in depression, Control: 91% probabil- Waiting list. ity CBT and 89% probabil- Measures: ity PST more 12-month cost-effective. follow-up Hollinghurst 133 Intervention: Beck PP: Societal et al. (2010) participants Usual case Depression (age 18-74 plus Inventory ICER (per Therapist- years) with therapist- (BDI): QALY): delivered new episode of delivered I: 14.7 (11.6) £17,173 online depression in online C: 22.2 (15.2) Cognitive primary care Cognitive Willingness to Behavioral across 55 Behavioral d: .560 pay threshold: Therapy for practices in Therapy for If value is depression UK. 68% up to ten 55- £20K/QALY, female. 72 in minute 56% probabil- intervention, sessions ity online 61 in control. within 4 Cognitive months. Behavioral Therapy more Control: cost-effective Usual care than usual plus 8-month care, and if waiting list. value is £30K, 71% probabil- Measures: ity more cost- 8 months effective. Gerhards et 267 Intervention: Changes in PP: Societal al. (2010) participants (1) Beck (age 18-65 Computerize Depression ICER (per “Colour Your years) with d Cognitive Inventory QALY):

Life” online mild to Behavioral (BDI-II): I1: €200712,806 computerized moderate Therapy I1: 11.10 (11.68) I2: €200714,837 Cognitive depressive (“Colour I2: 10.47 (10.60) C: €200713,563 Behavioral complaints for Your Life”) C: 9.77

95 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Therapy 3+ months and for 8 weekly (10.84) Willingness to without no sessions and pay threshold: primary care psychological 1 booster d1: .118 Even if value support for or session with d2: .065 €0/QALY, depression pharmacologic no No statistically 65% al treatment in professional significant probability preceding 3 support. differences in computerized months in the (2) “Colour effectiveness or Cognitive Netherlands. Your Life” QALY Behavioral 88 in plus outcomes. Therapy most intervention treatment as cost-effective. #1, 88 in usual. If value intervention increases to #2, 91 in Control: €80K, 40% control. Treatment as probability usual (advis- most effective ed to contact but treatment general as usual also practitioner, about 40% who was probability reminded of most effective. clinical guidelines).

Measures: 12 months Simon et al. 600 primary Intervention: Gain in PP: (2009) care patients (1) Tele- Depression- Healthcare with significant phone care Free Days Telephone depressive management (DFDs) INB (value of care symptoms, with up to 5 Compared to added DFDs management starting brief calls or Control: minus added and antidepressant mailings. I1: 29 (95% CI, outpatient telephone treatment in Average cost −6 to 63) costs): psychotherap U.S. 207 in $450/patient I2: 46 (95% CI, I1: If value of y for intervention more than 12 to 80) additional depression #1, 198 in usual care. DFD is $0-$20, intervention (2) d: NC benefit does #2, 195 in Telephone not exceed control. care manage- total ment plus 8 outpatient Cognitive cost of $676 Behavioral for 24 months. Therapy calls with 4 I2: Estimate if reinforce- value of

96 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness ment calls for additional up to 12 calls DFD is >$9, total. then net Average cost benefit is $650/patient positive and more than exceeds total usual care. outpatient cost of $397 Control: for 24 months. Usual care.

Measures: 24 months McCrone et 261 patients Intervention: Beck PP: Societal al. (2004) & (age 18-75 Usual care Depression Proudfoot et years) with plus Inventory Total Costs: al. (2004) depression, computer- (BDI): With lost mixed delivered I: 11.6 (9.6) employment

“Beating the depression and Cognitive C: 16.2 (10.1) I: £2000533 Blues” anxiety, or Behavioral (p<.001) (998) computerized anxiety Therapy C: £2000900 Cognitive disorders and (“Beating the d: .467 (2,428) Behavioral not receiving Blues”) with Therapy for face-to-face eight 50- Beck Anxiety Without lost anxiety and psychological minute Inventory employment depression in therapy from sessions. (BAI): I: £2000397 primary care 12 practices I: 10.6 (8.4) (589)

across UK. 138 Control: C: 12.8 (9.1) C: £2000357 in intervention, Usual care. (p=.06) (575) 123 in control. Measures: d: .251 Willingness to 6-month pay threshold: follow-up If value is £5K/QALY, 85% probability computerized Cogni- tive Behavior- al Therapy more cost- effective, and if value is £15K, >99% probability more cost- effective.

97 Depression

Other Treatments A few cost-effectiveness trials investigated less common interventions, including workplace occupational therapy, physical activity, and family psychoeducation. It is difficult to draw conclusions from these data without additional studies to confirm these initial findings.

Treatment Interventions For adults with depression and significant workplace absenteeism in the Netherlands, the addition of a workplace occupational therapy program to standard outpatient psychiatric care, including development of a work reintegration plan and individual and group sessions to improve needed skills, had a greater incremental net benefit ($14,860) than outpatient psychiatric treatment alone ($10,898) after a year. The workplace occupational therapy program had a 75.5% likelihood of being more cost-effective at the estimated wage used (Schene et al., 2007).

For adults with depression in the United Kingdom, an intervention intended to increase physical activity through periodic contact with a trained physical activity coordinator did not lead to any significant clinical benefits for depression outcomes but did increase physical activity more than usual care. Overall, the cost-effectiveness was £20,834 per QALY, which is within the range of £20,000 to £30,000 that is often used as a willingness to pay threshold (Chalder et al., 2012).

Secondary Prevention Interventions A study in Japan found that for preventing relapse in patients with depression in maintenance, family psychoeducation, including education, discussion, and problem-solving with primary family members, was significantly more clinically effective and also more cost-effective than usual care after nine months. Even if no value were assigned to a relapse-free day, there was a greater than 70% likelihood of being cost-effective. These general findings were estimated to hold true even if the intervention were 50% to 150% of the estimated costs (Shimodera et al., 2012). With an average participant age of 60 years, these results may also have implications for the older adult population discussed later.

Table 8. Other Treatments for Depression in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Treatment Interventions Schene et al. 57 adults with Intervention: Percent Meet PP: Employee (2007) depression Treatment as Criteria for and usual plus Major INB (value of Occupational significant Occupational Depressive work minus Therapy for workplace Therapy Disorder: healthcare work-related absenteeism including I: 44% service costs): Major in the development C: 29% I: $14,860 Depression Netherlands. of a work C: $10,898 29 in reintegration intervention, plan and Willingness to

98 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness 28 in control. individual pay threshold: and group At average sessions to hourly wage improve of $36.88, needed skills 75.5% for 6 months. probability addition of Control: Occupational Treatment as Therapy more usual cost-effective (outpatient than psychiatric treatment as treatment). usual alone.

Measures: 12 months Chalder et al. 152 patients Intervention: Beck PP: (2002) (age 18-69 Usual care Depression Healthcare years) with plus periodic Inventory Treating depression in contact (three (BDI): ICER (per depression primary care 45-60 minute I: 12.6 QALY): with physical across 65 face-to-face C: 13.5 £200920,834 activity practices in meetings and (NS) (TREAD) UK. 81 in ten 10-20 Willingness to intervention, minute phone d: NC pay threshold: 71 in control. calls) with If value is trained phys- No difference £20K/QALY, ical activity between 49% coordinator intervention probability over 6-8 and control for the addition months. any depression of physical Average cost measure. activity more £220-£259/ cost-effective person. Percent than usual Physically care alone, Control: Active: and if value is Usual care. I: 57.7% £30K, 57% C: 44.0% probability Measures: (OR>1) more cost- 12 months effective. Secondary Prevention Interventions Shimodera et 54 depression Intervention: Number of PP: al. (2012) patients (age Treatment as Relapse-Free Healthcare 18-85 years) in usual plus Days: Family maintenance family I: 272 (7.1) Total Costs: psychoeducati (i.e. no longer psychoeducati C: 214 (90.8) I: $20111,842

99 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness on to prevent within on with 4 (p=.009) C: $20112,638 depression diagnostic biweekly 2- relapse in threshold but hour sessions d: 1.185 ICER (per Japan still on of didactic relapse-free antidepressan lectures, Percent day):

t therapy) and group discus- Relapse: -$201113.72 their primary sion, and I: 8% family problem- C: 50% Willingness to members in solving with pay threshold: Japan. 24 in primary If no value per intervention, family mem- relapse-free 30 in control. bers. One day, still session is >70% prob- approx. ability family

$201150/ psychoeducati patient. on more cost- effective than Control: usual care. If Treatment as value $20, usual. >90% probability more Measures: cost-effective 9 months for 50%-150% pricing. If value is $30, then nearly 100% probability more cost-effective.

Postpartum Depression To date only one cost-effectiveness study for Postpartum Depression was available. In this large-scale study of over 4,000 postnatal women screened as high risk for depression across the United Kingdom, psychologically-informed interventions with either cognitive-behavioral or person-centered approaches delivered by trained health visitors were more cost-effective than health visitor usual care at £11,568 per QALY after six months, with over 80% likelihood of being more cost-effective within standard willingness to pay thresholds (Morrell et al., 2009).

Table 9. Behavioral Interventions for Postpartum Depression Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Morrell et al. 4,084 Intervention: Edinburgh PP: (2009) postnatal Health Postnatal Healthcare women in UK. visitors Depression

100 Depression

Psychological 595 women deliver Scale (EPDS): ICER (per interventions (17.3%) with psychologicall I: 9.2 (5.4) QALY): for postnatal an EPDS score y informed C: 11.3 (5.8) £200411,568 depression ≥12 at 6- interventions. (PoNDER weeks Average cost d: .375 Willingness to Trial) postnatal £35 less per pay threshold: classified as mother. Even if no “high risk.” 30 (1) Cognitive- value per treatment behavioral QALY, 65% clusters in approach. probability intervention (2) Person- intervention #1, 32 in centered more costintervention approach. effective, and #2, 38 in if value £20K- control. Control: £30K, just Health visitor over 80% usual care. probability intervention Measures: more cost- 6-month effective. follow-up

Depression in Older Adults Depression in older adults (age 65 years and older) is a serious concern, and some interventions specifically target prevention or treatment in this population. Additionally, interventions for depression and co-occurring medical conditions often included older populations as well, as discussed later.

Prevention Interventions Two trials in the Netherlands investigated stepped care programs for preventing onset of depression and anxiety in high-risk older adults (based on subclinical symptoms). A nurse-provided stepped care program of watchful waiting, bibliotherapy, problem-solving, and antidepressant medication halved the proportion of persons with a major disorder relative to usual care after a year (11.6% versus 23.8%). This stepped care program could be cost-effective at €4,367 per disorder-free year, depending on the willingness to pay threshold (van’t Veer-Tazelaar et al. 2010; van’t Veer-Tazelaar et al., 2009). However, for older adults in residential homes, a similar program of watchful waiting, self-help modules, life review, and physician consultation did not have any clinical or cost benefits relative to usual care and was not considered cost-effective at €85,521 per major disorder prevented after 10 months (Bosmans et al., 2014). The biggest difference between the two studied programs was that the former was in the community and the latter in residential homes, but it is unclear how this would explain the conflicting findings.

Treatment Interventions Cost-effectiveness findings for treating depression in older adults generally reflect the general adult population.

101 Depression

Interpersonal Therapy (IPT) still did not demonstrate cost-effectiveness over usual care after 12 month in the Netherlands (Bosmans et al., 2007). However, Cognitive Behavioral Therapy (CBT) did demonstrate the potential for cost- effectiveness over usual care for older adults in the United Kingdom after 10 months at £120-167 per improvement on a depression scale (Beck Depression Inventory). Cost-effectiveness would depend on the willingness to pay threshold (Holman et al., 2011; Serfaty et al., 2009). Overall, some types of in-person therapy may be cost-effective for older adults, but more studies are needed to compare them to antidepressant medication and establish this conclusively.

Additionally, therapist-guided Internet-delivered CBT for older adults with depression symptoms in Australia was more cost-effective than waiting list control immediately post-treatment at $4,392 per QALY, which had a greater than 95% likelihood of being cost-effective at the standard willingness to pay threshold of $50,000. Moreover, the clinical effects persisted up to 12 months later, which suggested the possibility of longer-term cost-effectiveness (Titov et al., 2015). This corroborates earlier findings for this type of intervention.

Lastly, a large-scale stepped Collaborative Care Management program that included Problem-Solving Therapy and medication management for patients with late-life Major Depression, Dysthymic Disorder (persistent mild depression for at least two years), or both disorders demonstrated clear clinical and cost benefits over usual care after two years. The intervention only cost $2,519 to $5,037 per QALY or $2.76 per depression-free day (DFD), and had a 25% likelihood of being dominant (Katon et al., 2005; Unützer et al., 2001). This trial adds to the list of subpopulations for which Collaborative Care Management was cost-effective.

Table 10. Behavioral Interventions for Depression in Older Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Prevention Interventions Bosmans et al. 185 older Intervention: Incidence: PP: Societal (2014) adults Stepped care Major screened for program to Depressive ICER (per Stepped care sub-threshold prevent onset Disorder QALY): program to depression of depressive I: .09 (SE .04) €200826,890 prevent and anxiety and anxiety C: .17 (SE .05) depression symptoms disorders with (NS) Willingness to and anxiety across 14 1 month of pay threshold: for older residential watchful d: .185 If value is adults in homes in the waiting then €0/QALY, residential Netherlands. 3-month Depression 13% probabil- homes 93 in cycles (self- and/or Anxiety ity stepped intervention, help module I: .20 (SE .06) care program 92 in control. with coaching, C: .19 (SE .05) more cost- 49% with cost life review, (NS) effective than data. general usual care. At

102 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness practitioner d: .019 highest consults for threshold, antidepressan Improvement max. 85% ts or therapist on Center for probability. referral). Total Epidemiologic costs €838 Studies ICER (per higher than Depression depression control (NS). Scale (CES-D): prevented):

I: 3.2 (SE .94) -€200810,293 Control: C: .88 (SE .79) Usual care. (NS) Willingness to pay threshold: Measures: d: .279 If value is €0/ 10-month depression follow-up No difference in prevented, incidence of 13% probabil- disorders or ity stepped any other care program outcomes. more cost- effective than usual care. If value is €10- 20K, 48%-72% probability. van’t Veer- 170 elderly Intervention: Proportion PP: Societal Tazelaar et al. persons (age Preventive With Major (2010 & 2009) 75+ years) stepped care Disorder: ICER (per with program in 3- I: 11.6% depression-/ Stepped care subthreshold month cycles C: 23.8% anxiety-free program to levels of with 4 steps year): prevent depressive or (watchful €20074,367 depression anxiety waiting, and anxiety symptoms in bibliotherapy, ICER (per 50% for high-risk the problem- reduced risk individuals in Netherlands. solving, of disorder late life 74% women. antidepressan onset):

50% with 2+ ts). Cost €2007532 chronic varied based conditions. 86 on steps, but in average cost Willingness to

intervention, €2007563.42/pa pay threshold: 84 in control. rticipant. If value €5K/ depression- or Control: anxiety-free Routine year, 57% primary care. probability

103 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness stepped care Measures: program more 12-month cost-effective follow-up than routine primary care; if value €10K- €20K, 86%- 94% probability more cost- effective. Treatment Interventions Titov et al. 52 older Intervention: Patient Health PP: (2015) adults (age Internet- Questionnaire Healthcare 60+ years) delivered -9 Item (PHQ- Therapist- with Cognitive 9): ICER (per guided depression Behavioral I: 3.96 (2.48) QALY): Internet- symptoms in Therapy over C: 12.68 (5.48) $4,392 (95% delivered Australia. 27 8 weeks with (p<.001) CI, <0 to Cognitive in brief weekly 63,962) Behavioral intervention, contact with a d: 2.191 Therapy 25 in control. clinical Willingness to for older adult psychologist Percent pay threshold: s with sympto via telephone Reliable If value is ms of or secure Improvement: $4,392/QALY, depression email. I: 50.0%-68.7% 50% Average total C: 5.8%-17.6% probability therapist time (p<.005) Internet- 45 minutes. delivered Percent Cognitive Control: Reliable Behavioral Waiting list. Recovery Therapy more (shift from cost-effective Measures: above to than waiting Post- below clinical list. If value is treatment cut-off): $50K, >95% I: 43.7%-68.7% probability C: 0-11.7% more cost- (p<.007) effective.

Differences persisted at 3 months and 12 months and remained significant when limited to

104 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness the clinical sample. Holman et al. 198 depressed Intervention: Beck PP: (2011) & patients (65+ Treatment as Depression Healthcare Serfaty et al. years) in usual plus Inventory (2009) primary care Cognitive (BDI-II): ICER (per 1- in UK. 79.4% Behavioral I: 18.3 (10.6) point Cognitive female. 67 in Therapy C1: 20.3 (9.0) improvement Behavioral intervention, (CBT) for up C2: 20.8 (10.5) in BDI):

Therapy in 65 in control to 12 sessions. £2008120-167 primary care #1, 66 in Average cost d1: .204 for depressed control #2. £427 more d2: .237 Willingness to older adults than control pay threshold: (p<0.001). If value is £115/1-point Controls: improvement (1) Usual care in BDI, >50% plus up to 12 probability sessions of CBT most talking cost-effective control. than treament (2) Usual care. as usual. If value is £270, Measures: 90% 10 months probability more cost- effective. Bosmans et al. 143 patients Intervention: Percent PP: Societal (2007) (age 55+ Interpersonal Remission on years) with Therapy Montgomery ICER (per Interpersonal depression delivered by Asberg MADRS Therapy for across 12 mental health Depression remission): elderly primary care workers for 10 Rating Scale -€2003131 patients with practices in sessions over (MADRS): depression the 5 months. I: 28.8% (45.6) ICER (per Netherlands. Average cost C: 34.7% (47.9) PRIME-MD 69 in €656/patient. (NS) recovered intervention, patient): 74 in control. Control: d: .126 €353,585 Usual care. Percent Measures: Recovery on 12 months PRIMary care Evaluation of Mental Disorders

105 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness (PRIME-MD): I: 45.2% (50.1) C: 45.0% (50.1) (NS)

d: .004 Katon et al. 1801 patients Intervention: Difference in PP: (2005) & (age 60+ 12-month Number of Healthcare Unützer et al. years) with stepped Depression- (2001) Major Collaborative Free Days ICER (per Depression Care (DFDs): QALY): Improving (17%), Management I-C: 107 (95% $2,519-$5,037 Mood Dysthymic program with CI, 86 to 128) Promoting Disorder depression ICER (per Access to (30%), or both care manager d: NC DFD): Collaborative (53%) from 18 who provided $2.76 Treatment primary care education, (IMPACT) clinics in the support of Collaborative U.S. 906 in antidepressan Care intervention, t medications, Management 895 in control. and Problem- for late-life Solving depression Therapy. Average cost $591/ patient more than control.

Control: Usual care.

Measures: 24 months

Depression in Comorbid Medical Populations Depression is linked to greater healthcare utilization exceeding the costs of treating depression or any co-occurring diseases (e.g., Simon et al., 2007). This may reflect the negative impact of depression on self-care and treatment adherence for medical conditions. Despite this, limited studies have assessed behavioral interventions for comorbid populations; those that have generally find behavioral interventions to be cost-effective or even cost-saving. One study looked at an incurable illness (multiple sclerosis), while the remainder focused on chronic conditions influenced by lifestyle factors such as coronary disease and diabetes.

106 Depression

Multiple Sclerosis For co-occurring multiple sclerosis and low mood (analogous to subthreshold depression) in the United Kingdom, group Psychological Adjustment Treatment demonstrated significant clinical improvements over usual care after 8 months. Psychological Adjustment Treatment focused on identifying symptoms of distress and introducing strategies to improve mood and cost £118 per incremental improvement on a depression measure (Beck Depression Inventory). This treatment had a 93% likelihood of being more cost-effective than usual care if the value were £118 per incremental improvement (Humphreys et al., 2013).

Coronary Disease For patients with persistent depressive symptoms after an acute coronary syndrome (e.g., heart attack, unstable angina), enhanced depression care with patient preference for Problem-Solving Therapy (PST) alone, antidepressants alone, or PST plus antidepressants were all cost-saving compared to usual care after six months (Ladapo et al., 2012; Davidson et al., 2010). These findings differ from PST in the general adult population, although patient preference could be key.

For patients waiting for first time elective coronary bypass graft surgery in the United Kingdom, the addition of the cognitive behavioral HeartOp Programme to reduce psychological symptoms was more cost-effective than routine nurse counseling alone at £288.83 per QALY after 8 weeks, with over 90% likelihood of cost-effectiveness up to the typical willingness to pay threshold of £30,000 (Furze et al., 2009). Meanwhile, for patients screened for depression after coronary bypass graft surgery, a nurse-led and telephone-delivered Collaborative Care Management program (“Bypassing the Blues”) with psychoeducation, medication management, and therapist referral as needed led to significantly greater clinical improvements than usual care after 12 months. If one high-cost outlier was excluded, the intervention was cost-saving at $21,591 per QALY. Overall, there was a 68% likelihood the program was dominant and 90% likelihood it was more cost-effective than usual care at a willingness to pay threshold of $20,000 per QALY (Donohue et al., 2014; Rollman et al., 2009).

Diabetes Multiple Collaborative Care Management programs in primary care demonstrated cost-effectiveness for co-occurring depression and diabetes.

A multicomponent stepped care Depression Management Program with psychotherapy, pharmacotherapy, or both, depending on needs of patient, had an incremental net benefit of $5.20 saved per depression-free day (DFD) compared to usual care after two years. Even if there were no value ascribed to a DFD, cost-savings were still estimated at $300 per patient, and if value were greater than $8 per DFD, there was an estimated 95% likelihood of cost benefit (Simon et al., 2007). Similarly, a culturally-adapted Collaborative Care Management program (Multifaceted Diabetes and Depression Program) including Problem-Solving Therapy and/or medication plus follow-up telephone calls for a primarily Hispanic population with co-occurring depression and diabetes improved rates of response and remission. This CCM program was

107 Depression clearly more cost-effective than enhanced usual care at only $4,053 per QALY after two years (Hay et al., 2012; Ell et al., 2010).

Multiple Disorders The two remaining studies for diabetes include other co-occurring illnesses. For depression and poorly controlled diabetes and/or coronary heart disease, a multi-condition Collaborative Care Management program with a case manager to target multiple disease risk factors simultaneously found similar savings at $1,773 saved per QALY or $5.26 saved per depression-free day (DFD) after two years. The CCM program had a 97.7% probability of being cost-effective within standard willingness to pay thresholds (Katon et al, 2012). Finally, for chronically ill older adults in the Netherlands with diabetes or chronic obstructive pulmonary disease and co-occurring minor, major, or dysthymic depression, a Minimal Psychological Intervention delivered at the patient’s home was cost- saving compared to usual care at €11,508 to €12,534 saved per QALY after one year. The Minimal Psychological Intervention had a 82% likelihood of being cost- effective within standard willingness to pay thresholds (Jonkers et al., 2009). This paralleled findings for Minimal Contact Psychotherapy in the general adult population (Smit et al., 2006).

Table 11. Behavioral Interventions for Depression in Comorbid Medical Populations Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Multiple Sclerosis Humphreys et 151 patients Intervention: Reduction in PP: al. (2013) with multiple Psychological Beck Healthcare sclerosis and Adjustment Depression Psychological low mood in Treatment on Inventory ICER (per 1- Adjustment UK. 72 in how to (BDI-II): point Treatment for intervention, recognize I: -2.38 (4.72) improvement multiple 79 in control. distress C: -.67 (3.44) in BDI-II): sclerosis and symptoms (p=.01) £2009118 low mood and strategies to improve d: .419 Willingness to mood for 6 pay threshold: group If value is sessions (8 £118/1-point people) over improvement 12 weeks. in BDI-II, 93% Average cost probability £248/patient. group Psycho- logical Adjust- Control: ment Treat- Usual care. ment more cost-effective Measures: than usual 8-month care. follow-up

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Coronary Disease Donohue et al. 189 patients Intervention: Hamilton PP: (2014) & screened for Nurse- Rating Scale Healthcare Rollman et al. depression provided and for (2009) following phone- Depression (H ICER (per coronary delivered RS-D): QALY): ‘Bypassing the artery bypass Collaborative I: 9.0 (SE .7) $54,605 Blues’ phone- surgery in Care C: 11.4 (SE .7) delivered Coll U.S. 90 in Management (p<.001) 1 high-cost aborative Car intervention, program outlier excluded e 99 in control. including d: .279 −$21,591 Management f psychoeducati or treating on with Short Form-36 Willingness to depression workbook, (SF-36) pay threshold: after coronary initiation/adj Mental If value is artery bypass ustment of Component $20K/QALY, graft surgery antidepressan Summary 90% ts, referral to (MCS) probability mental health I: 50.1 (SE 1.0) Collaborative specialists, or C: 46.2 (SE Care more “watchful 1.1) cost-effective waiting” for 8 (p=.02) than usual months. care. Overall, Biweekly 15- d: .302 68% 45 minute probability sessions for 2- Physical Collaborative 4 months, Component Care then contact Summary dominant. every 1-2 (PCS) months. I: 44.0 (SE .8) ICER (per Estimated cost C: 41.4 (SE .8) DFD): $460/patient. (NS) −$4

Control: d: .264 1 high-cost Usual care. outlier excluded Percent −$59 Measures: Improvement 12 months (8 (≥50% Decline months for on HRS-D): clinical I: 50.0% outcomes) C: 29.6% (p<.001) Ladapo et al. 157 patients Intervention: Beck PP: (2012) & (mean age 60) Enhanced Depression Healthcare Davidson et with acute depression Inventory al. (2010) coronary care with (BDI): Total Costs:

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness syndrome and patient At 3 months I: $1,857 Coronary persistent preference for: I: 19.0 (95% C: $2,797 Psychosocial depressive (1) Problem- CI, 17.5 to (p=0.09) Evaluation symptoms for Solving 20.4) Studies 3 months after Therapy. C: 19.6 (95% Willingness to (COPES) discharge in (2) CI, 18.2 to pay threshold: depression U.S. 80 in Antidepressan 21.1) If value is care after intervention t use. $30K/QALY, acute group, 77 in (3) Both 1 & 2. d: NC 98% coronary control. probability syndrome Control: At 9 months enhanced Usual care. I: 13.2 (95% depression CI, 11.1 to care more Measures: 15.3) cost-effective 6 months C: 17.7 (95% than usual CI, 15.6 to care. 19.7) Because the d: NC interventions are cost-saving Percent on average, no Hospitalizatio mean cost- ns for Major effectiveness Adverse ratio exists. Cardiac Events and Heart Failure: I: 5.5% C: 16% Furze et al. 182 Intervention: Cardiac PP: (2009) preoperative Routine nurse Depression Healthcare patients counseling Scale (CDS): HeartOp waiting for plus HeartOp I: 81.69 ICER (per Programme first time Programme of C: 93.37 QALY): prior to elective brief cognitive (p=.008) £2004288.83 coronary coronary behavioral bypass graft bypass graft intervention, d: NC Willingness to surgery to surgery in including a 2- pay threshold: reduce UK. 88 in part booklet, If value is psychological intervention, relaxing <£30K/QALY symptoms 94 in control. program, , >90% goals diary, probability and facilitator HeartOp follow-up via Programme phone. more cost- Average cost effective than

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness of routine nurse £1.73/patient. counseling alone. Control: Routine nurse counseling, including facilitator follow-up via phone.

Measures: 8-week follow-up Diabetes Simon et al. 278 adults Intervention: Depression- PP: (2007) with diabetes Multicompon Free Days Healthcare and current ent depression (DFDs): Systematic depressive management I: 412 (202) ICER (per depression disorder in program with C: 359 (207) DFD): treatment for primary care specialized -$5.20 people with in U.S. 135 in nurses d: .259 comorbid intervention, delivering 12- Willingness to depression 143 in control. month pay threshold: and diabetes stepped care If value is program $0/DFD, still including incremental psychotherap net benefit y, pharma- with cost cotherapy, or savings of both, depend- approx. $300/ ing on needs patient, and if of patient. value is $8+/ DFD, 95% Control: probability of Continued cost benefit. usual care.

Measures: 24 months Hay et al. 387 diabetes Intervention: Symptom PP: (2012) & Ell et patients with Socio- Checklist Healthcare al. (2010) clinically culturally Depression significant adapted Scale (SCL- ICER (per Multifaceted depression in Collaborative 20): QALY): Diabetes and U.S. 96.5% Care Response (50% $4,053

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Depression Hispanic. 193 Management reduction) Program in program I: 89 (61.8) Willingness to (MDDP) intervention, including C: 60 (43.8) pay threshold: stepped 194 in control. Problem- (p<.001) If value is Collaborative Solving $5K/QALY, Care Therapy d: .549 >50% Management and/or probability program medication, Remission Collaborative monthly (score<0.5) Care phone follow- I: 58 (40.3) Management up for treat- C: 48 (35.0) more cost- ment main- (p=.04) effective than tenance, enhanced relapse d: .266 usual care, prevention, and if value is and $12K, >90% navigational probability support for 12 more cost- months. effective. Average cost $515/patient.

Control: Enhanced usual care with educational pamphlets and resource list.

Measures: 24 months Multiple Disorders Katon et al. 214 patients Intervention: Symptom PP: (2012) with TEAMcare Checklist Healthcare depression multi- Depression TEAMcare and poorly condition Scale (SCL- ICER (per multi- controlled Collaborative 20): QALY): condition diabetes, Care I: .88 (.66) -$1,773 Collaborative coronary Management C: 1.04 (.69) (95% CI, Care heart disease, program with −2,878 to Management or both in nurse care d: .237 2,878) program for primary care manager to depression across 14 provide ICER (per and poorly clinics in U.S. treatment for DFD): controlled 106 in multiple -$5.26 (95%

112 Depression

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness diabetes or intervention, disease risk CI, −29.76 to coronary 108 in control. factors. 19.17) heart disease Estimated cost $1,224/patient Willingness to pay threshold: Control: If value Enhanced <$20K/ usual care. QALY, 97.7% probability Measures: multi- 24 months condition Collaborative Care Management more cost- effective than usual care. Jonkers et al. 228 older Intervention: Depression- PP: Societal (2009) adults (age Minimal Free Days 60+ years) Psychological (DFDs) per ICER (per Depression in with diabetes Intervention year: QALY):

Elderly with or chronic delivered at I: 184 (12) €2004−12,534 to Long-Term obstructive the patient’s C: 163 (11) −11,508 Afflictions pulmonary home by (DELTA) Mini disease and nurses. d: 1.826 Willingness to mal co-occurring Average cost pay threshold: Psychological mild, major, €337/person. Euroqol If value is Intervention or dysthymic (EQ5D) €20K/QALY, in chronically depression in Control: Utility: 82% ill elderly the Usual care. I: .62 (.02) probability patients with Netherlands. C: .56 (.02) Minimal depression 110 in Measures: Psychological intervention, 12-month d: 3.000 Intervention 118 in control. follow-up more cost- effective than usual care, and if value is €80K, 89% probability more cost- effective.

LIMITATION AND FUTURE DIRECTIONS Given the high economic burden of depressive disorders, it is imperative to identify cost-effective solutions, and some psychosocial treatments offer promising results. Given the wide variety of behavioral interventions, from

113 Depression providing enhanced, stepwise, and/or collaborative care in addition to traditional treatment, to using innovative self-driven and distance-based treatment protocols, more studies are needed that standardize the different elements of care and compare these varied options directly with each other. This is particularly relevant given the high rates of patients with depression treated in primary care settings.

Clearly, more studies are needed for patient groups outside of the general adult population, including children and adolescents, older adults (age 65 years and older), and patients with comorbid medical conditions. The duration of studies may be of particular relevance. For instance, studies available in adolescents tended to favor pharmacotherapy over psychotherapy; however, it has been demonstrated in other contexts that medication may have more immediate short- term effects that might be dominant in earlier time periods but may not persist after treatment discontinues. In anxiety disorders (see Chapter 1), one study demonstrated cost-effectiveness for medication alone in the first 3 months but for Cognitive Behavioral Therapy alone in the following 12 months.

Additionally, research studies are needed to further elucidate the unique cost- effective prevention and treatment options for other diagnoses, including Persistent Depressive Disorder, Major Depressive Disorder with Seasonal Pattern, Major Depressive Disorder with Peripartum Diagnosis, Premenstrual Dysphoric Disorder, and Disruptive Mood Dysregulation Disorder. Valuable work investigating depressive symptoms that do not meet diagnostic criteria (e.g., minor depression, subthreshold depression) may elucidate additional options to alleviate the costs associated with these depressive symptoms and provide opportunities for both primary and secondary prevention.

Most cost-effectiveness studies for depression only consider improvements in depression symptoms but depression treatments may have additional benefits, such as increased work productivity, reduced healthcare costs, and improved health behaviors. Without assessing these outcomes in cost-effectiveness studies, it is difficult to ascertain the true societal cost benefits that may exist. Thus, some interventions might be more cost-effective than estimated in these trials due to unmeasured benefits on associated health or workplace outcomes.

KEY POINTS In general, there is strong evidence for cost-effective behavioral interventions for treating depression across most populations other than young people.

Children and Adolescents • For prevention in children and adolescents at high risk for depression, group Cognitive Behavioral Therapy (CBT) was more cost-effective than usual care but a classroom-based CBT intervention was not. • For treatment in children and adolescents with depression, including those with persistent or treatment-resistant depression, antidepressant medication remained more cost-effective than CBT within typical willingness to pay thresholds. However, all studies were only 12 to 24 weeks long.

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Adults • Interpersonal Therapy (IPT) and Cognitive Behavioral Therapy (CBT) may be more cost-effective than usual care but do not appear to be more cost- effective than antidepressant medication. Unlike for children, CBT was a cost- effective addition for treatment-resistant depression and may also be a cost- effective addition for relapse prevention, depending on the willingness to pay threshold. CBT may also be cost-effective for certain subpopulations and as adjunctive care, supporting clinical guideline recommendations that psychotherapy be offered as an effective alternative to antidepressant medication based on patient preference. • Generic or non-directive therapy, short-term counseling, and supportive care were not cost-effective as independent treatment options in primary care compared to usual care, CBT, or antidepressant medication over longer time durations. • Collaborative Care Management and other structured care delivery programs in primary care, including stepped care versions, were consistently cost- effective, including for major depression, minor depression, persistent depression, high utilizers of general medical services, veterans, older adults, and comorbid populations across multiple medical disorders, with effects persisting up to two years later. • Brief therapy-based treatments including Minimal Contact Psychotherapy and Cognitive Self-Therapy have the potential to be more cost-effective than usual care for prevention in high-risk patients and for treatment, which may be due to the lower costs of implementation, but were not cost-effective compared to CBT. More studies are needed to corroborate these initial findings. • Telehealth-based therapies via telephone and Internet, whether with virtual professional support or completely self-driven, are reliably more cost- effective than usual care but are pending comparisons to antidepressant medication and in-person therapies. The majority were CBT-based, but a Problem-Solving Therapy (PST)-based version appeared equally cost- effective. • A few other interventions, like occupational therapy and physical activity for treatment and family psychoeducation for relapse prevention, may be cost- effective but more studies are needed to corroborate these initial findings.

Special Populations • For women who have just given birth and are at high risk for depression, the addition of psychologically-informed interventions was more cost-effective than usual care, although more studies are needed. • For prevention in older adults at high risk for depression or anxiety, two stepped care programs had conflicting results compared to usual care, with one having the potential to be cost-effective, but the other having no clinical or cost differences. • For treatment in older adults, cost-effectiveness findings paralleled those in the general adult population: Interpersonal Therapy (IPT) was not cost-

115 Depression

effective but both in-person and Internet-based Cognitive Behavioral Therapy (CBT) and Collaborative Care Management were cost-effective compared to usual care. However, no studies compared CBT to antidepressant medication. • For depression and co-occurring medical conditions (multiple sclerosis, coronary disease, diabetes, chronic obstructive pulmonary disease), almost all treatments tested were clearly cost-effective or even cost-saving. • Specifically, for comorbid multiple sclerosis and low mood, Psychological Adjustment Treatment may be more cost-effective than usual care, depending on the willingness to pay threshold and pending further studies. • Specifically, for comorbid coronary disease and depressive symptoms, Problem-Solving Therapy, antidepressant medication, or both combined were all cost-saving after an acute coronary syndrome; a cognitive behavioral program was cost-effective for patients waiting for elective coronary bypass graft surgery; and Collaborative Care Management programs were cost- effective for patients after coronary bypass graft surgery and more generally. • Specifically, for comorbid depression and diabetes, multiple Collaborative Care Management programs were cost-effective or cost-saving, including a stepped care version, a culturally-adapted version, and a multi-condition version to target multiple disease risk factors. • Specifically, for chronically ill adults with diabetes or coronary obstructive pulmonary disease and co-occurring depression, a Minimal Psychological Intervention delivered at the patient’s home was cost-saving.

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SUPPLEMENT: GENERAL MENTAL HEALTH PROBLEMS

ABSTRACT In addition to behavioral interventions focused on persons with one diagnosable disorder (e.g., Anxiety Disorder, Depressive Disorder), some interventions target general mental health problems and can include mixed populations with multiple types of symptoms and/or disorders (primarily anxiety and depression). These interventions provide psychotherapy by non-specialists in primary care.

Generic or non-directive counseling was not cost-effective compared to usual care after four or nine months. Across three studies, Problem-Solving Treatment did not lead to any significant clinical benefits compared to usual care. In one study it was dominated for both quality of life and anxiety and depression symptoms. In the second study, it was cost-saving for quality of life, but not for anxiety and depression symptoms. In the third study, it was cost-effective for indirect costs of lost productivity, but not for direct healthcare costs. Brief Psychodynam- ic-Interpersonal Therapy for patients with unresponsive mental health problems for at least six months had significantly lower costs than usual psychiatric care, suggesting it could be cost-effective. Self-help Cognitive Behavioral Therapy facilitated by a practice nurse had similar clinical and cost outcomes to usual care after three months, suggesting it was no more cost-effective. Overall, the limited data do not demonstrate consistent cost-effectiveness for the use of psychotherapeutic interventions among mixed populations for improving general mental health problems. Nonetheless, some of the tested interventions showed promise for improving other outcomes, such as quality of life, reduction in absenteeism, or future health care utilization. Some found similar clinical effects at similar costs to usual care, which suggest the potential benefits for these interventions, particularly in cases where patients prefer these treatments to usual care.

BACKGROUND ON GENERAL MENTAL HEALTH PROBLEMS Persons with general mental health problems frequently present in primary care rather than seeking out specialist treatment (e.g., psychiatric services). Moreover, these mental health symptoms may cause psychological distress without meeting the diagnostic criteria for a specific neuropsychiatric disorder. Given this, interventions designed for these settings often combine patients with multiple types of symptoms and/or disorders. This supplement reviews cost-effectiveness studies targeting multiple mental health problems (excluding psychotic symptoms) that do not fit in the preceding chapters. Most commonly, these include Anxiety Disorders or anxiety symptoms and Depressive Disorders or depression symptoms. For further details on these disorders, their economic burden, and clinically effective interventions, please refer to Chapters 1 and 2, respectively.

COST-EFFECTIVENESS OF INTERVENTIONS A review of counseling for mental health and psychosocial problems in primary care concluded that counseling was associated with short-term clinical benefits but was without clear long-term clinical benefits or any cost benefits relative to usual care in the United Kingdom (Bower et al., 2011). All cost-effectiveness studies reviewed here were for psychosocial treatments including counseling. The majority studied interventions in primary care, but one intervention targeted

126 General Mental Health patients with high utilization of psychiatric care. Notably, all studies are from the Netherlands and United Kingdom.

Generic Counseling Two studies investigated generic or non-directive counseling for patients with diverse mental health problems (primarily anxiety and depression) in primary care in the United Kingdom. This counseling intervention emphasized listening rather than advising. After four months, brief generic counseling with a person- centered approach was equally clinically effective as usual care on all measures, including for anxiety and depression. While cost-effectiveness was not calculated, total healthcare costs were similar, ranging from £71.21 to £81.23 for generic counseling and from £89.67 to £109.51 for usual care (Harvey et al., 1998). Thus, there was no data to indicate brief generic counseling would be any more or less cost-effective than usual care.

Similarly, after 9 months, non-directive counseling to help patients with emotional problems express feelings, clarify thoughts, and restate or reframe difficulties was equally clinically effective to usual care on all measures. Whether the intervention was more or less costly depended on length of time; the initial three months were more expensive than usual care, but the following sixth months were less expensive due to fewer direct costs. While the intervention remained more costly than usual care over the full nine months, if direct costs remained lower over time, this intervention could have cost benefits over a longer period of time (Friedli et al., 2000; Friedli et al., 1997).

Table 1. Generic Counseling for General Mental Health Problems Method and Clinical Cost- Study Participants Intervention Outcomes Effectiveness Friedli et al. 136 patients Intervention: Beck Depres- PP: Societal (2000 & with emotion- Non-directive sion Invento- 1997) al problems counseling ry (BDI): Direct Costs (mainly de- using Rogeri- I: 9.7 (8.5) (per patient): Non- pression then an model for C: 13.5 (10.7) First 3 months directive anxiety) across 6-12 sessions (NS) I: £207.94 counseling in 14 practices in over 12 C: £192.15 primary care UK. 70 in in- weeks. d: .396 Next 6 months for patients tervention, 66 I: £127.19 with emo- in control. Control: Brief Symp- C: £298.24 tional prob- Routine care tom Invento- Total 9 months lems with general ry – General I: £308.63 practitioner. Severity In- C: £474.30 dex (GSI): Measures: I: .7 (.6) Indirect Costs 9 months C: .9 (.7) (per patient) (NS) First 3 months I: £352.14 d: .308 C: £220.65 Next 6 months

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Method and Clinical Cost- Study Participants Intervention Outcomes Effectiveness Clinical In- I: £402.37 terview C: £331.73 Schedule Total 9 months (CIS): I: £808.70 I: 12.2 (12.7) C: £468.50 C: 15.6 (12.7) (NS) Total Direct and Indirect Costs d: .268 (per patient): First 3 months Social Ad- I: £583.21 justment C: £421.12 Scale: Next 6 months I: 2.0 (.5) I: £542.97 C: 2.2 (.5) C: £629.97 (NS) Total 9 months I: £1,191.27 d: .400 £963.33

Intervention more expensive for first 3 months, less for next 6 months, and more again (only due to indirect costs) for total 9 months. Harvey et al. 162 patients Intervention: Improvement PP: Healthcare (1998) with diverse Generic brief in Hospital mental health counseling Anxiety and Total Costs: Counseling problems (ex- with person- Depression I: £71.21-81.23 in primary cluding psy- centered ap- Scale C: £89.67-109.51 care for di- chosis and proach (e.g., (HADS): verse mental phobic condi- listening ra- Anxiety sub- health prob- tions) in UK. ther than ad- scale lems 111 in inter- vising) in I: 3.0 (95% CI, vention, 51 in primary care 1.9 to 3.9) control. with up to six C: 3.5 (95% 50-minute CI, 2.1 to 4.9) sessions. (NS)

Control: Depression Routine care subscale with general I: 2.7 (95% practitioner. CI, 1.6 to 3.7) C: 3.4 (95%

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Method and Clinical Cost- Study Participants Intervention Outcomes Effectiveness Measures: CI, 1.8 to 4.9) 4-month fol- (NS) low-up Significant improvements within groups, but not between groups.

Problem-Solving Therapy Three studies focused on Problem-Solving Treatment (PST) delivered by mental health or community nurses in the Netherlands or United Kingdom. Nurses trained patients with mental health problems in problem-solving skills to help them address psychosocial challenges and interpersonal issues, and set and work toward goals. In all three studies, there were no significant clinical differences between PST and usual care; however, cost findings were more variable.

First, PST by trained community nurses for patients with emotional disorders (e.g., complaints of anxiety, tension, depressed mood, irritability, sleep disturbance, and somatic symptoms) was equally clinically effective as usual care after 26 weeks. The cost findings were more interesting, with the intervention incurring significantly higher healthcare costs ($132 versus $87) and significantly lower productivity losses based on total days off work (estimates of £81 for 4.35 days versus £932 for 16.23 days). Thus, cost-effectiveness for PST will depend on the cost measures included in the calculation (Mynors-Wallis et al., 1997).

Second, PST by trained mental health nurses was compared against generic care by trained mental health nurses at matched intensity, as well as to usual care. The interventions targeted patients with a new episode of depression, anxiety, and/or reaction to life difficulties. As before, there were no clinical differences after 26 weeks, including on measures of anxiety and depression. Moreover, there were no significant changes in quality-adjusted life years (QALY) for PST or generic counseling compared to usual care. Given the higher total costs to implement PST or generic counseling, both interventions can be considered dominated by usual care (Kendrick et al., 2006).

Third, PST by trained mental health nurses for patients with mental health problems had mixed cost-effectiveness results depending on the measure. In terms of quality of life, PST was cost-saving at €65,045 per QALY, which dominated usual care at all willingness to pay thresholds. In terms of anxiety and depression symptoms, it cost €8,676 per incremental improvement on an anxiety and depression measure (Hospital Anxiety and Depression Scale), which had a 95% likelihood of being cost-effective if no value is ascribed to this improvement. However, cost-effectiveness will ultimately depend on the willingness to pay threshold (Bosmans et al., 2012).

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Table 2. Problem-Solving Therapy for General Mental Health Problems Method and Clinical Cost- Study Participants Intervention Outcomes Effectiveness Bosmans et 121 patients Intervention: Reduction in PP: Societal al. (2012) with mental Problem- Hospital health prob- Solving Anxiety and ICER (per Problem- lems across 12 Treatment for Depression QALY): Solving practices in 4-6 sessions Scale Dominant Treatment the Nether- delivered by (HADS): (−€65,045) for mental lands. 56 in mental health I: -3.1 (SE 1.3) health prob- intervention, nurses in C: -2.9 (SE Willingness to lems 65 in control. primary care. 1.0) pay threshold: (NS) Cost-effective at Control: d: .022 all values per Usual care. QALY.

Measures: ICER (per 1- 9-month fol- point improve- low-up ment in HADS): €8,676

Willingness to pay threshold: If value is €0/1- point improvement in HADS, 95% probability intervention more cost- effective than usual care. For higher values, probability decreases to 57%. Kendrick et 184 patients Interventions: Clinical In- PP: Societal al. (2006) (age 18-65 (1) Problem- terview years) with a Solving Schedule – Total Cost of Problem- new episode Treatment Revised (CIS- Care:

Solving of anxiety, de- from trained R): I1: £2003631 (501) Treatment pression, mental health I1: 12.8 (12.0) I2: £2003599 (366) for common and/or reac- nurses with 1 I2: 10.4 (9.4) C: £2003316 (327) mental tion to life dif- hour-long ini- C: 10.1 (10.9) health disor- ficulties in tial assess- (NS) Total Cost of ders UK. 71 in in- ment plus up Days Off Work:

tervention #1, to 5 follow- d1: -.236 I1: £20035,880 62 in interven- up sessions. d2: -.030 (12,727)

tion #2, 51 in Average cost I2: £20033,694 control. £315/patient. Hospital (8,464)

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Method and Clinical Cost- Study Participants Intervention Outcomes Effectiveness

(2) Generic Anxiety and C: £20033,787 care from Depression (7,540) mental health Scale (HADS) nurses with 1 Anxiety Sub- ICER (per hour-long ini- scale: QALY): tial assess- I1: 8.68 (4.54) Dominated ment plus up I2: 8.19 (3.76) to 5 follow- C: 7.57 (4.28) No significant up sessions. (NS) improvement in Average cost QALY for either £283/patient. d1: -.252 intervention. Nei- d2: -.154 ther can be con- Control: sidered cost- Usual care effective compared from GPs. to usual care.

Measures: 26-week follow-up Mynors- 70 patients Intervention: Clinical In- PP: Societal Wallis et al. with an emo- Problem- terview (1997) tional disorder Solving Ther- Schedule Total Healthcare (e.g., com- apy from a (CIS): Costs: Problem- plaints of anx- trained com- I: 9.3 (7.9) I: £132.0 (55.3) Solving iety, tension, munity nurse. C: 9.2 (7.2) C: £86.6 (54.9) Treatment depressed Average cost (NS) (p=.002) for emotion- mood, irrita- £61/patient. d: .013 al disorders bility and Total Days Off given by sleep disturb- Control: General Work: community ance, and so- Treatment as Health Ques- I: 4.35 (10.35) nurses in matic symp- usual from tionnaire C: 16.23 (23.82) primary care toms) for at GP. (GHQ): (p=.054) least 1 month I: 4.4 (5.6) in primary Measures: C: 2.8 (3.8) Estimated Cost care in UK. 40 26-week fol- (NS) of Total Days in interven- low-up d: .333 Off Work: tion, 30 in con- I: £81 trol. Social Ad- C: £932 (p=.034) justment Scale (SAS): Intervention was I: 2.1 (.4) more expensive in C: 2.0 (.4) terms of (NS) healthcare costs d: .250 but saved more in terms of lost productivity.

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Psychodynamic-Interpersonal Therapy Lastly, one study from the United Kingdom focused on patients with mental health problems (primarily depression) in psychiatric treatment who had not responded to usual psychiatric care for at least six months. These patients were considered high utilizers of psychiatric services. The intervention added brief Psychodynamic-Interpersonal Therapy to usual psychiatric care, which is similar to Interpersonal Therapy (see Chapter 2) but further emphasizes the patient- therapist relationship and downplays the interpretation of transference. After six months, the total direct healthcare costs were much lower in the intervention compared to usual care alone ($1,959 versus $2,424); cost-effectiveness was not calculated as the researchers concluded it was unlikely the psychotherapy would cost more than usual care alone (Guthrie et al., 1999).

Table 3. Psychodynamic-Interpersonal Therapy for General Mental Health Problems Method and Clinical Cost- Study Participants Intervention Outcomes Effectiveness Guthrie et al. 110 patients Intervention: Symptom PP: Healthcare (1999) with nonpsy- Brief Psycho- Checklist (SCL- chotic mental dynamic- R-90): Total Direct brief Psy- health prob- Interpersonal Global Severity Treatment and chodynamic- lems (75.5% Therapy for 8 Index (GSI) Non- Interperson- depressive) in weekly ses- I: 1.76 (SE .13) Treatment al Therapy psychiatric sions plus C: 2.05 (SE .16) Costs: for high uti- treatments usual care. d: .327 I: $1,959 lizers of psy- who were un- C: $2,424 chiatric ser- responsive to Control: Depression sub- vices usual care for Usual care scale An incremental at least 6 from a psy- I: 2.16 (SE .14) cost-utility ratio months in UK. chiatrist. C: 2.44 (SE .17) was not calcu- 55 in interven- d: .295 lated, as results tion, 55 in con- Measures: suggested psy- trol. 6-month fol- Short-Form chotherapy was low-up Health Survey unlikely to cost (SF-36): more than Physical Func- treatment as tion subscale usual. I: 61.8 (SE 3.87) C: 51.0 (SE 5.67) d: .372

Mental Health subscale I: 39.5 (SE 2.46) C: 33.5 (SE 3.70) d: .320

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Self-Help Cognitive Behavioral Therapy Since patients do not always have access to psychotherapy, one study investigated a supervised self-help Cognitive Behavioral Therapy (CBT) program facilitated by 1-3 contacts with a trained practice nurse. The intervention was provided for patients with mild to moderate mental health problems in the United King- dom. After one month, the intervention did demonstrate greater clinical effects; however, these differences did not persist at three months. Mental health costs were not significantly different. Despite short-term benefit, the intervention was not cost-effective (Richards et al., 2003).

Table 4. Self-Help Cognitive Behavioral Therapy for General Mental Health Problems Method and Clinical Cost- Study Participants Intervention Outcomes Effectiveness Richards et 87 patients Intervention: Clinical Out- PP: Mental al. (2003) with mild to Cognitive comes in Healthcare moderate Behavioral Routine Supervised mental health Therapy- Evaluation Total Costs: self-help problems based self- (CORE-OM): I: £191.80 Cognitive (anxiety help book fa- I: 1.24 (.82) (220.86) Behavioral and/or de- cilitated by C: 1.51 (.87) C: £231.43 Therapy in pression practice nurs- (NS) (184.64) primary care symptoms) in es for up to 3 (NS) UK. 47 in in- appointments d: .320 tervention, 40 (two 1 week in control. apart, third 3 Percent Reli- months later). able and Clin- ically Signifi- Control: cant Change: Usual care. 1 month I: 29% Measures: C: 12% 3-month follow-up 3 months I: 29% C: 33%

KEY POINTS • For diverse mental health problems (primarily anxiety and depression and excluding psychosis), the psychosocial interventions tested here do not demonstrate strong or consistent clinical effectiveness. They do not have large effects on mental health symptoms, and thus are not likely to be cost-effective for mental health symptom reduction. As demonstrated in the chapters on Anxiety Disorders and Depressive Disorders, behavioral interventions limited to specific symptoms/disorders may be more impactful; however, interventions for patients presenting with concurrent symptoms/disorders warrant further study.

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• Despite similar clinical effectiveness to usual care, some of the tested interventions showed promise for improving other outcomes, such as quality of life, reduction in absenteeism, or future health care utilization. Some found similar clinical effects at similar costs to usual care. While these interventions may not be favored over current practice for improving mental health symptoms, their other benefits may warrant their use. In the case where the interventions were both clinically and cost neutral, information regarding patient preference for care would be helpful.

• Across two studies, generic and non-directive counseling of active listening rather than advising did not demonstrate any significant clinical benefits over usual care. Cost data indicate cost-effectiveness after four or nine months, although studies of longer duration are needed.

• Across three studies, Problem-Solving Treatment (PST) delivered by trained nurses did not demonstrate any significant clinical benefits compared to usual care and cost data was variable. In one study, PST was dominated by usual care in terms of both quality of life and anxiety and depression symptoms after 26 weeks. In another, PST was cost-saving in terms of quality of life. Here, cost-effectiveness would depend on the willingness to pay threshold. Lastly, while healthcare costs were significantly higher for PST compared to usual care, the costs associated with lost productivity due to total days off work were significantly lower.

• One study focused on patients with mental health problems who were unresponsive to usual psychiatric care for at least six months, comparing the addition of brief Psychodynamic-Interpersonal Therapy to usual psychiatric care with psychiatric care alone. The direct healthcare costs were significantly lower in the intervention after six months, suggesting cost-effectiveness.

• One study considered a supervised Cognitive Behavioral Therapy (CBT) self- help book facilitated by 1-3 contacts with a practice nurse, and found similar clinical and cost outcomes to usual care after three months, suggesting it was not cost-effective despite clinical improvements after one month.

REFERENCES

Bosmans JE, Schreuders B, van Marwijk HW, Smit JH, van Oppen P, van Tulder MW. Cost-effectiveness of problem-solving treatment in comparison with usual care for primary care patients with mental health problems: a randomized trial. BMC Fam Pract. 2012 Oct 10;13:98.

Bower P, Knowles S, Coventry PA, Rowland N. Counselling for mental health and psychosocial problems in primary care. Cochrane Database Syst Rev. 2011 Sep 7;(9):CD001025.

134 General Mental Health

Friedli K, King MB, Lloyd M. The economics of employing a counsellor in general practice: analysis of data from a randomised controlled trial. Br J Gen Pract. 2000 Apr;50(453):276-83. Erratum in: Br J Gen Pract 2000 May;50(454):408.

Guthrie E, Moorey J, Margison F, Barker H, Palmer S, McGrath G, Tomenson B, Creed F. Cost-effectiveness of brief psychodynamic-interpersonal therapy in high utilizers of psychiatric services. Arch Gen Psychiatry. 1999 Jun;56(6):519-26.

Harvey I, Nelson SJ, Lyons RA, Unwin C., Monaghan S, & Peters, TJ. A randomized controlled trial and economic evaluation of counselling in primary care. Br. J. Gen. Pract. 1998 Mar;48(428):1043-1048.

Kendrick T, Simons L, Mynors-Wallis L, Gray A, Lathlean J, Pickering R, Harris S, Rivero-Arias O, Gerard K, Thompson C. Cost-effectiveness of referral for generic care or problem-solving treatment from community mental health nurses, compared with usual general practitioner care for common mental disorders: Ran- domised controlled trial. Br J Psychiatry. 2006 Jul;189:50-9.

Mynors-Wallis L, Davies I, Gray A, Barbour F, Gath D. A randomised controlled trial and cost analysis of problem-solving treatment for emotional disorders given by community nurses in primary care. Br J Psychiatry. 1997 Feb;170:113-9.

Richards A, Barkham M, Cahill J, Richards D, Williams C, Heywood P. PHASE: a randomised, controlled trial of supervised self-help cognitive behavioural therapy in primary care. Br J Gen Pract. 2003 Oct;53(495):764-70. van Roijen LH, van Straten A, Al M, Rutten F, Donker M. Cost-utility of brief psychological treatment for depression and anxiety. Br J Psychiatry. 2006 Apr;188:323-9.

135 Bipolar Disorders

CHAPTER 3: BIPOLAR DISORDERS

ABSTRACT Bipolar Disorder is characterized by episodes of mania and depression. Preva- lence of Bipolar Disorder is estimated from 1.0% to 3.3% of the U.S. population, and the corresponding economic burden is estimated at $151 billion in direct and indirect costs annually. Both prevalence and economic burden are likely to be significant underestimates since they do not account for subthreshold symptoms or misdiagnosed patients.

First-line treatment is pharmacotherapy, although recommendations differ for treating patients in current manic or depressive episodes or patients in remission. Psychosocial interventions are only recommended as adjunctive treatment, but combined with medication they can increase the likelihood and speed of recovery and thus have the potential to improve overall cost-effectiveness. Based on single studies, brief Group Psychoeducation was more cost-effective than longer Cognitive Behavioral Therapy but was not compared to standard care. A Multi- component Care Program cost more and was more clinically effective for treating manic symptoms than usual care in patients experiencing significant mood symptoms. This suggests cost-effectiveness could improve by limiting the intervention to this population. The addition of Cognitive Behavioral Therapy to standard care was more cost-effective than standard care alone for relapse prevention. More studies are needed to draw meaningful conclusions.

BACKGROUND ON DISORDER Bipolar Disorder (formerly known as Manic Depressive Disorder) is characterized by intense emotional states that occur in distinct episodes of mania and depression, including unusual shifts in mood, energy, and functioning.

During manic episodes, the person may feel extremely happy and outgoing and/or extremely irritable. S/he may have additional energy, manifested in talking fast; racing thoughts; being easily distracted; increasing activities; being overly restless; sleeping less; and behaving impulsively. Meanwhile, during depressive episodes, the individual may feel extremely sad or hopeless and/or lose interest in activities s/he previously enjoyed, manifested in feeling tired or slow; having difficulty concentrating, remembering, and making decisions; feeling restless; feeling irritable; changing eating, sleeping, or other habits; and contem- plating death and suicide, including attempting suicide (NIMH, 2014).

While Bipolar Disorder is used as an umbrella term, there are few common types of the disorder included in the most recent version of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5): • Bipolar I Disorder is characterized by manic or mixed manic and depressive episodes that persist for at least seven days, and depressive episodes that typically persist for at least two weeks. • Bipolar II Disorder is characterized by a pattern of depressive episodes and hypomanic episodes (less severe than manic episodes), without full-blown manic episodes or mixed manic and depressive episodes.

136 Bipolar Disorders

• Cyclothymic Disorder is a milder form of Bipolar Disorder that does not meet criteria for Bipolar I or II, characterized by hypomanic episodes (less severe than manic episodes) and mild depressive episodes over at least two years.

Bipolar Disorder is primarily distinguished from Major Depressive Disorder by intermittent manic episodes. However, when depressive episodes occur first, Bi- polar Disorder may be mistaken for Major Depressive Disorder, which can lead to misdiagnosis and sub-optimal treatment. It is posited that up to half of all Ma- jor Depressive Disorders diagnoses may be misdiagnosed cases of Bipolar II Dis- order that have gone undetected because the patients were not evaluated for long enough to identify any hypomanic episodes (Angst et al., 2004).

PREVALENCE OF DISORDER In the United States, lifetime prevalence for Bipolar I Disorder is 1.0%, for Bipolar II Disorder is 1.1%, and for subthreshold Bipolar Disorder (i.e. similar to Cyclo- thymic Disorder, with bipolar symptoms not meeting diagnostic criteria) is 2.4%. Another estimate limited only to Bipolar I Disorder found a lifetime prevalence of 3.3% (Grant et al., 2005). Since most studies are limited to Bipolar I and II Dis- orders, cases of subthreshold Bipolar Disorder and/or Cyclothymic Disorder may go undetected or misdiagnosed, indicating prevalence rates are likely underestimates (Merikangas et al., 2007).

Chronicity is common, with some symptoms often persisting in the intervals between manic/depressive episodes. This chronicity is due, in part, to the limited efficacy of treatment (e.g., partial remission, continued impairment), the duration of remission episodes decreasing over time, and the frequency of relapses both with and without treatment (Fagiolini et al., 2013; Kleinman et al., 2003). Moreo- ver, Bipolar Disorders are highly comorbid: 95.8% to 97.5% of persons with Bipo- lar I or II Disorder and 88.4% of persons with subthreshold Bipolar Disorder have another neuropsychiatric illness, most commonly Anxiety Disorders, which complicates both symptoms and treatments (Merikangas et al., 2007).

ECONOMIC BURDEN OF DISORDER Annual costs of Bipolar I and II Disorder were estimated to be $151 billion in the United States in 2009; $30.7 billion in direct costs and the remaining $120.3 billion in indirect costs (Dilsaver et al., 2009). These estimates do not include the costs associated with subthreshold Bipolar Disorder and/or Cyclothymic Disorder, which would increase the estimates substantially given their higher prevalence. Indirect costs include decreased productivity, increased morbidity, and earlier mortality due to suicide and related medical disorders (e.g., diabetes, cardiovascular disease; Merikangas et al., 2007). Employment is also significantly impacted, with a national estimate of 37% unemployment among persons with Bipolar Disorder (Woods, 2000).

Many factors are not fully included in calculating the overall economic burden. Since symptoms often start in childhood and adolescence, the costs are likely higher due to the adverse impact on education and occupational training (Dil- saver et al., 2009). In adulthood, medical risk factors and common medical condi-

137 Bipolar Disorders tions associated with Bipolar Disorder are under-detected and under-treated, which contribute to poorer long-term outcomes and additional associated costs (Kupfer et al., 2005). More than half of persons with Bipolar Disorder do not seek help in the first five years from their initial symptoms (Woods, 2000). In general, persons with Bipolar Disorder utilize healthcare services more than those with Major Depressive Disorder or other chronic medical conditions (Dean et al., 2004), although the costs of Bipolar Disorder were about 70% of those associated with Schizophrenia as of 1991 (Woods, 2000).

Lastly, Bipolar Disorder is correlated with lower health-related quality of life, even outside of the manic and depressive episodes (i.e. not experiencing active symptoms), similar to other chronic medical conditions. Depressive symptoms appear to contribute more to this lower health-related quality of life than manic ones (Dean et al., 2004)

CLINICALLY EFFECTIVE INTERVENTIONS First-line treatment for Bipolar Disorder is pharmacotherapy, with different medication recommendations for active manic and depressive episodes and for maintenance during remission. Psychotherapy is only recommended as adjunctive treatment, but has been shown in large randomized trials to increase the likelihood and speed of recovery in patients with Bipolar Disorder receiving pharmacotherapy (Miklowitz et al., 2007). Cognitive Behavioral Therapy, Inter- personal and Social Rhythm Therapy, and Intensive Family-Focused Therapy similarly improve effectiveness and quicken recovery compared to psychoeducation in patients receiving medication.

Cognitive Behavioral Therapy (CBT) helps people identify and target maladaptive thoughts and behaviors, including understanding differences in depressive and manic episodes and when a shift in mood occurs. Group Psychoeducation, as the name implies, educates persons about the symptoms, causes, and treatments of their disorder in a group setting. The group can be others with Bipolar Disorder or family members. Family Therapy specifically incorporates family members, especially those in caregiving roles. In addition to education, the therapy targets the relationships between the person with Bipolar Disorder and their family members. Interpersonal and Social Rhythm Therapy (IPSRT) augments therapy focused on interpersonal interactions with a focus on maintaining consistency in sleep/wake cycles, meal times, and social interactions. Electroconvul- sive therapy (ECT) may be used in severe cases where other treatments have not been effective, with the patient’s consent and in consultation with a psychiatrist.

For depressive episodes or to delay relapse during remission, CBT, IPSRT, or Family Therapy may be useful adjunctive treatments to pharmacotherapy. For manic episodes, no specific psychotherapies are indicated. Group Psychoeduca- tion may also be effective for relapse prevention during remission. No cost- effectiveness studies of Family Therapy, IPSRT, or ECT are currently available.

COST-EFFECTIVENESS OF INTERVENTIONS A limited number of cost-effectiveness studies for Bipolar Disorder are available to date. A prior review of clinical- and cost-effectiveness of psychosocial inter-

138 Bipolar Disorders ventions noted that therapies that initially seem more cost- and time-intensive are often more clinically effective and therefore may be cost-effective over longer durations. More studies over a longer duration are needed to compare the treatment modalities (Miklowitz & Scott, 2009). In our review, we only identified three studies using a randomized, controlled design: one on adjunctive psychotherapies, one on enhanced care management, and one on relapse prevention.

Treatment Interventions In Canada, both adjunctive Cognitive Behavioral Therapy (CBT) and Group Psy- choeducation were similarly clinically effective after 72 weeks; however, CBT was more expensive, suggesting it was the less cost-effective of the two options. Importantly, the CBT was delivered for a much longer duration (20 sessions) than the Group Psychoeducation (6 sessions), which in part explains the higher costs (Parikh et al., 2012). No conclusions of overall cost-effectiveness of Group Psychoeducation can be made without comparing it to standard care alone or by establishing a willingness to pay threshold.

A Multicomponent Care Program to enhance patient care including Group Psy- choeducation as well as monthly phone monitoring, provider feedback, and follow-up care significantly decreased the level and duration of manic symptoms but had no significant effect on depressive symptoms compared to usual care after two years. Importantly, these effects were limited to patients who had significant mood symptoms when they entered the program. The intervention cost significantly more than usual care, but cost-effectiveness was not computed other than an incremental cost of $1,251 for 5.5 additional weeks free from significant manic symptoms (Simon et al., 2006). Given that the Multicomponent Care Pro- gram only had clinical benefits for a subset of patients, cost-effectiveness may be improved if it were limited to those with significant mood symptoms. Future versions could also try to modify the program to improve depressive symptoms, in addition to the manic symptoms. .

Secondary Prevention Interventions In the United Kingdom, one study looked at relapse prevention by adding Cog- nitive Behavioral Therapy (CBT) to standard treatment. This enhanced care was more clinically effective at decreasing relapse and decreasing days with bipolar episodes with comparable costs after 30 months. There was an 80% likelihood that the addition of CBT would be more cost-effective than standard treatment alone even if there were no value ascribed to an additional Bipolar-Free Day (BFD), and up to 85% likelihood if the value was greater than £10 per BFD. This rate appears similar to those used for Depression-Free Days (see Chapter 2). The clinical effects were greater in the first 12 months, with the cost-effectiveness probabilities increasing to 85% and 90% respectively (Lam et al., 2005).

139 Bipolar Disorders

Table 1. Behavioral Interventions for Bipolar Disorder Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Treatment Interventions Parikh et al. 204 partici- Interventions: Longitudinal PP: Interven- (2012) pants (age 18- (1) Individual Interval Fol- tion 64 years) with Cognitive Be- low-up Eval- Adjunctive Bipolar I or II havioral uation (LIFE): Intervention psychothera- Disorder on Therapy for Depression Costs (per py for Bipolar mood- twenty 50- scale participant): Disorder: stabilizing minute ses- (p=.89) I1: CAD$1,200 Cognitive Be- medication sions. Mania scale I2: CAD$180 havioral across 4 cen- (2) Brief (p=.96) Therapy vs. ters in Cana- Group Psy- Using the same Group Psy- da. 95 in in- choeducation No differences hourly rate for choeducation tervention #1, for six 90- in clinical effec- both interven- 109 in inter- minute ses- tiveness for ei- tions, Cognitive vention #2. sions. ther depression Behavioral or mania. Therapy costs Measures: more than 72 weeks Group Psy- choeducation. Simon et al. 331 partici- Intervention: Number of PP: (2006) pants with Bi- Usual care Weeks with Healthcare polar I or II plus Multi- Symptoms Multicompo- Disorder component (Psychiatric Total Costs: nent Care across 4 clin- Care Program Status Rat- I: $8,046 Program for ics in U.S. 156 with nurse ing≥3): (5,974) Bipolar Dis- in interven- care managers Manic symp- C: $6,743 order tion, 175 in including toms (6,695) control. Group Psy- I: 19.2 (20.2) (p=.06) choeducation, C: 24.7 (24.3) monthly (p=.01) Incremental phone moni- Cost (per 5.5 toring, pro- d: .247 Manic-Free vider feed- Weeks): back, and fol- Depressive $1,251 (95% low-up care symptoms CI, $55-$2,446) for two years. I: 47.6 (29.7) C: 50.7 (31.9) Majority of in- Control: (p=.45) cremental costs Usual care. due to interven- d: .101 tion (~$800). Measures: 2 years Benefits limited to patients with symptoms at baseline.

140 Bipolar Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Secondary Prevention Interventions Lam et al. 83 persons Intervention: Days with Bi- PP: (2005) (age 18-70 Cognitive Be- polar Epi- Healthcare years) with havioral sodes: Cognitive Be- Bipolar I Dis- Therapy I: 95.3 (152.1) Total Costs: havioral order in UK. (CBT) in addi- C: 201.0 (95.3) I: £10,352 Therapy for 43 in intervention to stand- (13,464) relapse pre- tion, 40 in ard treatment. d: .854 C: £11,724 vention from control. (12,061) Bipolar I Dis- Control: Relapse Rates: (NS) order Standard I: 64% treatment. C: 84% Willingness to (p=.012) pay threshold: Measures: If value is 30 months £0/additional Bipolar-Free Day (BFD), 80% probability Cognitive Behavioral Therapy more cost-effective than standard treatment, and if value is >£10, 85% probability more cost- effective.

LIMITATIONS AND FUTURE DIRECTIONS The biggest limitation is the lack of sufficient studies to draw meaningful conclusions. The complexities of Bipolar Disorder also add to the need for more specific and nuanced studies to disentangle what psychosocial interventions might be the most effective – clinically and economically – for different symptoms and in different contexts.

Like many neuropsychiatric disorders, the early onset, frequent comorbidities, and lifetime chronicity of Bipolar disorder all complicate treatment. Innovation in effective interventions is needed, as Bipolar Disorder is known for the persistence of symptoms during remission, for remission duration decreasing over time, and for the frequency of relapses despite treatment.

As the pharmacology recommendations reveal, treatment for Bipolar Disorder differs depending on whether the patient is experiencing manic episodes, depressive episodes, or remission. In the cost-effectiveness studies reviewed here, it

141 Bipolar Disorders is evident that the psychotherapy recommendations may also vary in these differing contexts or, at the very least, may need to be further customized to different symptoms to maximize their efficacy. Aligning treatment to address current manic and depressive symptoms should have the added benefit of improving cost-effectiveness.

Meanwhile, both clinical and cost data are lacking for subthreshold Bipolar Dis- order and/or Cyclothymic Disorder, even though the available data suggest Cy- clothymic Disorder is more prevalent that Bipolar I and II Disorders combined. The possibility that some persons with diagnoses of Major Depressive Disorder may actually be misdiagnosed cases of Bipolar Disorder further indicate the importance of understanding bipolar symptoms and how to treat them, even when diagnostic criteria are not met. Suboptimal treatment or the absence of treatment due to misdiagnosis or lack of diagnosis will add to the long-term cost burden.

KEY POINTS • Further studies need to replicate results before conclusions can be made, including using standard cost-effectiveness measures to facilitate comparisons.

• In one study, brief Group Psychoeducation was equally clinically effective and less expensive than longer-term Cognitive Behavioral Therapy, but was not compared for similar treatment durations or to standard care to determine overall cost-effectiveness.

• In one study, a Multicomponent Care Program reduced frequency and severity of manic symptoms (but not depressive symptoms) in patients who entered with significant mood symptoms (but not for those with symptoms in control) and also cost more than usual care. Cost-effectiveness was not calculated, but it was estimated to cost $1,251 for an additional 5.5 manic-free weeks. Limiting the intervention to bipolar patients experiencing significant manic symptoms could conceivably improve cost-effectiveness.

• In one study, the addition of Cognitive Behavioral Therapy to standard care had a high likelihood of being more cost-effective than standard care alone for relapse prevention in terms of additional days free of bipolar symptoms.

REFERENCES

Angst J. Bipolar disorder--a seriously underestimated health burden. Eur Arch Psychiatry Clin Neurosci. 2004 Apr;254(2):59-60.

Dean BB, Gerner D, Gerner RH. A systematic review evaluating health-related quality of life, work impairment, and healthcare costs and utilization in bipolar disorder. Curr Med Res Opin. 2004;20(2):139-54.

Dilsaver SC. An estimate of the minimum economic burden of bipolar I and II disorders in the United States: 2009. J Affect Disord. 2011 Mar;129(1-3):79-83.

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Fagiolini A, Forgione R, Maccari M, Cuomo A, Morana B, Dell'Osso MC, Pelle- grini F, Rossi A. Prevalence, chronicity, burden and borders of bipolar disorder. J Affect Disord. 2013 Jun;148(2-3):161-9.

Grant BF, Stinson FS, Hasin DS, Dawson DA, Chou SP, Ruan WJ, Huang B. Prev- alence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2005 Oct;66(10):1205-15.

Kleinman L, Lowin A, Flood E, Gandhi G, Edgell E, Revicki D. Costs of bipolar disorder. Pharmacoeconomics. 2003;21(9):601-22.

Kupfer DJ. The increasing medical burden in bipolar disorder. JAMA. 2005 May 25;293(20):2528-30.

Lam DH, McCrone P, Wright K, Kerr N. Cost-effectiveness of relapse-prevention cognitive therapy for bipolar disorder: 30-month study. Br J Psychiatry. 2005 Jun;186:500-6.

Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM, Petukhova M, Kessler RC. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007 May;64(5):543-52.

Miklowitz DJ, Otto MW, Frank E, Reilly-Harrington NA, Wisniewski SR, Kogan JN, Nierenberg AA, Calabrese JR, Marangell LB, Gyulai L, Araga M, Gonzalez JM, Shirley ER, Thase ME, Sachs GS. Psychosocial treatments for bipolar depression: a 1-year randomized trial from the Systematic Treatment Enhancement Program. Arch Gen Psychiatry. 2007 Apr;64(4):419-26.

Miklowitz DJ, Scott J. Psychosocial treatments for bipolar disorder: cost- effectiveness, mediating mechanisms, and future directions. Bipolar Disord. 2009 Jun;11 Suppl 2:110-22.

National Institute for Mental Health (NIMH). Bipolar Disorder. Retrieved No- vember 21, 2014, from http://www.nimh.nih.gov/health/topics/bipolar-disorder/index.shtml.

Parikh SV, Zaretsky A, Beaulieu S, Yatham LN, Young LT, Patelis-Siotis I, Macqueen GM, Levitt A, Arenovich T, Cervantes P, Velyvis V, Kennedy SH, Streiner DL. A randomized controlled trial of psychoeducation or cognitive- behavioral therapy in bipolar disorder: a Canadian Network for Mood and Anxi- ety treatments (CANMAT) study [CME]. J Clin Psychiatry. 2012 Jun;73(6):803-10.

Simon GE, Ludman EJ, Bauer MS, Unützer J, Operskalski B. Long-term effectiveness and cost of a systematic care program for bipolar disorder. Arch Gen Psy- chiatry. 2006 May;63(5):500-8.

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Woods SW. The economic burden of bipolar disease. J Clin Psychiatry. 2000;61 Supp 13:38-41.

144 Schizophrenia

CHAPTER 4: SCHIZOPHRENIC SPECTRUM DISORDERS

ABSTRACT Schizophrenic Spectrum Disorders include Schizophrenia and related disorders with similar symptomologies. The defining characteristic is psychosis (i.e. a disconnection from reality such as hallucinations or delusions). These disorders are known for persistent chronicity and frequent relapses. Prevalence in the United States was estimated from 0.3% to 1.6%. The economic burden—limited to Schiz- ophrenia—was estimated at $62.7 billion in direct and indirect costs annually, which must be an underestimate since it does not include the full spectrum of disorders.

First-line treatment is antipsychotic medication, with additional medication to treat specific symptoms or comorbid conditions as needed. Psychosocial interventions are only recommended as adjunctive treatment. Due to the complexity of these disorders, optimal psychosocial interventions are likely to vary depending on illness phase (e.g., acute psychosis versus maintenance) and specific symptoms (e.g., positive, negative, cognitive).

Current cost-effectiveness data fall into two broad categories: studies on psychosis, including but not limited to persons with Schizophrenic Spectrum Disorders, and studies on Schizophrenic Spectrum Disorders, including but not limited to persons with psychosis. For first or early episodes of psychosis, Assertive Fol- low-Up and Cognitive Behavioral Therapy-Based Social Recovery were cost- effective compared to standard care. Similarly, an intensive program with Asser- tive Community Treatment, Family Psychoeducation, and Social Skills Training for two years remained cost-effective compared to standard community care after five years. For acute, persistent, and medication-resistant psychosis, Cogni- tive Behavioral Therapy also appeared to be cost-effective, with clinical improvements and minimal or no cost differences over standard care alone. Finally, for acute psychosis, Compliance Therapy to improve medication adherence was cost-effective over the short-term but did not appear to be over the longer term.

For auditory hallucinations, a Hallucination-Focused Integrative Therapy (including Cognitive Behavioral Therapy) tended toward being cost-effective. For cognitive and social difficulties, Cognitive Remediation Therapy was not cost- effective. Group Art Therapy also was not cost-effective over generic activity group sessions or usual care. Lastly, for patients with Schizophrenic Spectrum Disorders and co-occurring substance misuse, an integrated treatment including Cognitive Behavioral Therapy and a motivational intervention for substance use and Family Therapy for caregivers had the potential to be more cost-effective than routine care alone.

More studies are needed, but the available data demonstrate the economic value of psychosocial interventions for these complex and debilitating psychotic disorders.

145 Schizophrenia

BACKGROUND ON DISORDER Several disorders fall under the umbrella of Schizophrenic Spectrum Disorders, although available data focus on Schizophrenia or specific symptoms.

The defining characteristic of Schizophrenic Spectrum Disorders, sometimes known as Psychotic Disorders, is Psychosis (i.e. disconnection from reality) but they also include positive symptoms, negative symptoms, and cognitive symptoms. The positive or psychotic symptoms include disconnection from reality with hallucinations (e.g., perception of sensory experiences, most often auditory, that do not exist), delusions (e.g., persistent false beliefs, often paranoia, that do not change with new and/or contradicting information), thought disorders (e.g., disorganized thinking), and movement disorders (e.g., lack of movement or response to others). These symptoms can come and go and be experienced at different severities. The negative symptoms disrupt typical emotions and behaviors, and include self-neglect, lack of pleasure, lack of ability to begin and sustain planned activities, limited speech, and flat and dull tone while speaking. Lastly, cognitive symptoms may include difficulty focusing or paying attention, dimin- ished ability to comprehend and make decisions, and problems retaining and using new information (NIMH, 2014).

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) includes the following sub-types: • Schizophrenia, the most well known diagnosis, is characterized by the symptoms described above for a minimum of 6 months. • Schizoaffective Disorder is characterized by the symptoms described above and by affective disorder symptoms, with mood that is overly positive (e.g., manic symptoms) or overly depressed/irritable (e.g., depressive symptoms). • Schizophreniform Disorder is characterized by the symptoms described above but with a shorter duration of at least 1 month but less than 6 months. • Delusional Disorder is limited to the psychotic symptom of delusions (e.g., persistent false beliefs, often paranoia) for at least 1 month and the absence of any other schizophrenic symptoms. • Brief Psychotic Disorder is characterized by at least one of the psychotic symptoms for at least one day and less than a month, usually non-recurring. If it lasts longer or recurs, another diagnosis may be appropriate.

Meanwhile, Schizoid Personality Disorder and Schizotypal Personality Disorder are classified as Personality Disorders (see Chapter 5).

PREVALENCE OF DISORDER Due to limited data and under-representation in epidemiological studies, lifetime prevalence for Schizophrenic Spectrum Disorders in the United States is difficult to estimate. There is a possible range of 0.3% to 1.6% for Schizophrenia and Schizophreniform Disorder (Kessler et al., 2005a). Looking at multiple national health insurance claims databases (i.e. limited to persons receiving medical care), the 12-month prevalence of diagnosed Schizophrenia was estimated at 0.51% or 1.5 million people in 2002 (Wu et al., 2006), which falls within the range above. Notably, it is estimated that up to 80% of persons with Schizophrenia will expe-

146 Schizophrenia rience it as persistent chronic illness (Nicholl et al., 2010). Looking specifically at non-affective Psychosis, nationally representative data estimates lifetime prevalence at 1.5%. Of these, 79.4% had at least one additional neuropsychiatric disorder (Kessler et al., 2005b).

ECONOMIC BURDEN OF DISORDER Schizophrenic Spectrum Disorders incur significant healthcare and societal costs, in part due to decreased productivity, increased morbidity, and earlier mortality. The total annual excess costs of Schizophrenia in the United States were estimated to be $62.7 billion in 2002, with total direct healthcare costs of $22.7 billion (36%), total direct non-healthcare costs (e.g., police enforcement, homeless shel- ters) of $9.3 billion (15%), and total indirect costs of $32.4 billion (52%; Wu et al., 2005). Since this estimate does not include the full spectrum of disorders, it appears to be a significant underestimate.

The chronicity and high rate of relapse of Schizophrenia impacts overall costs. Prevalence peaks during a person’s most productive working years (Wu et al., 2006), which can contribute to employment difficulties and other indirect societal costs. Long-term care management for Schizophrenia is complex, with the majority of healthcare costs directly associated with diagnosis and treatment (Nicholl et al., 2010). A global review estimated that one-third to two-thirds of total healthcare costs are due to inpatient care (Knapp et al., 2004). Meanwhile, a nationally representative study using an insurance claims database (i.e. limited to persons receiving medical care) found that the overall economic burden for direct medical costs was significantly higher in newly diagnosed patients than in chronic patients, with a significant proportion of costs for all patients due to inpatient care as well (Nicholl et al., 2010). Schizophrenia also places a significant burden on family members and caregivers, which may be included in societal costs. However, no standard methodology for determining the costs associated with caregiver burden has been established yet (Awad et al., 2008).

CLINICALLY EFFECTIVE INTERVENTIONS Given the broad range of symptoms, the recommended guidelines are to tailor treatment to each individual’s needs. However, primary treatment is always antipsychotic medication. Additional medication to target specific symptoms or comorbid conditions may also be recommended. Psychosocial interventions are only recommended as adjunctive treatment (i.e. in addition to medications), although the complexity of symptoms, recurrence, and relapse, and issues with medication adherence and treatment engagement, all indicate the value of incorporating psychosocial interventions to contribute to overall care management.

As with Bipolar Disorder (see Chapter 3), treatment recommendations can vary depending on the phase of illness. In the acute psychosis phase, the primary foci of psychosocial interventions are to reduce stressors or triggers in the environment and relationships, and to foster structure, predictability, tolerance, and support. It can be useful to involve and support family members. For stabilization and maintenance phases, the foci are to support the return to normal life and activities and to prevent relapse.

147 Schizophrenia

Clinically effective interventions for the maintenance phase (i.e. remission) include Family Interventions, Assertive Community Treatment, Supported Em- ployment, Social Skills Training, and Cognitive Behavioral Therapy (CBT). Fami- ly Interventions (e.g., Family Psychoeducation) include support and training to improve patient outcomes and family wellbeing. Assertive Community Treat- ment (e.g., Assertive Follow-Up) provides active community-based care. To support adjustment, Supported Employment provides guidance and resources to help the patient gain skills and successfully navigate the employment process. Social Skills Training helps develop or improve social skills. No cost- effectiveness studies of Supported Employment are currently available. CBT, including CBT-Based Social Recovery, provides tools to target undesired cognitions and behaviors across positive, negative, and cognitive symptoms.

Cost-effectiveness studies are also available for therapies not included in current treatment guidelines, including Compliance Therapy, Cognitive Remediation Therapy, Group Art Therapy, and Hallucination-Focused Integrative Therapy. Compliance Therapy, which is based on Motivational Interviewing and cognitive approaches, focuses on increasing compliance with treatment, especially medication. Cognitive Remediation Therapy targets some common cognitive deficits, such as attention, working memory, planning, and executive functioning, which in turn can also improve social functioning. Group Art Therapy, as the name de- scribes, provides group settings to create art as personal expression. Hallucina- tion-Focused Integrative Therapy targets persistent hallucinations with a combined treatment including CBT, coping training, and psychoeducation.

COST-EFFECTIVENESS OF INTERVENTIONS The few cost-effectiveness studies available to date fall into two broad categories: 1) studies focused on psychosis, which include but are not limited to persons with Schizophrenic Spectrum Disorders, and 2) studies focused on Schizophrenic Spectrum Disorders (which also often includes psychosis).

Psychosis Studies of psychosis often include mixed populations including but not limited to persons with clinical diagnoses of Schizophrenic Spectrum Disorders, affective disorders (e.g., Bipolar Disorder), and/or other neuropsychiatric disorders. Note that all studies included here are from the United Kingdom.

Two studies tested interventions for persons experiencing their first or early episodes of psychosis. First, an early intervention for first episodes via Assertive Follow-Up by a multidisciplinary team was both more effective and less expensive than standard care, dominating cost-effectiveness in terms of both quality of life and returning to work after 18 months (McCrone et al., 2010). Second, Cogni- tive Behavioral Therapy (CBT)-Based Social Recovery, combining CBT techniques and vocational case management for persons with early psychosis who were unemployed or underemployed, was more than 50% likely to be more cost- effective than vocational case management alone at £18,844 per QALY after nine months. This is within the standard willingness to pay threshold of £20,000 per QALY (Barton et al., 2009; Fowler et al., 2009). Overall, the addition of psychoso-

148 Schizophrenia cial interventions during initial episodes of psychosis demonstrated cost- effectiveness.

For persons with psychosis admitted into inpatient services, Compliance Thera- py to improve compliance to antipsychotic medications via Motivational Inter- viewing and cognitive approaches was more clinically effective and less expensive than non-specific counseling services during the first six months. However, by 18 months, there were no differences in health care costs between patients that received non-specific counseling versus Compliance Therapy during the six months after inpatient treatment (Healey et al., 1998; Kemp et al., 1998). For persons with medication-resistant psychosis, the addition of CBT to standard care appeared to be cost-effective, with significant clinical improvements and no significant differences in associated costs after 18 months (Kuipers et al., 1998). Even in cases with more complicated psychosis (e.g., unemployment or underem- ployment, inpatient hospitalization, medication-resistance), psychosocial interventions show promise for being cost-effective adjunctive treatment options.

Table 1. Behavioral Interventions for Psychosis Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness McCrone et al. 144 partici- Intervention: Manchester PP: Public (2010) pants in first Early inter- Short Assess- Sector episode of vention ser- ment of Quali- Early inter- psychosis or vice with As- ty of Life Total Costs: vention with who have sertive Fol- (MANSA): I: £200411,685 Assertive Fol- previously low-Up pro- I: 59.3 (12.6) (14,032) low-Up for discontinued vided by a C: 53.3 (12.4) C: £200414,062 psychosis service in UK. multidiscipli- (p=.025) (18,004) 71 (72% schiz- nary team (NS) ophrenia) in dedicated to d: .480 intervention, managing ear- ICER (per ad- 73 (67% schiz- ly psychosis. Percent Voca- ditional voca- ophrenia) in tional Recov- tional recov- control. Control: ery: ery): Standard care. I: 32.8% Dominant C: 21.0% Measures: (NS) ICER (per 1- 18-month fol- point im- low-up provement on MANSA): Dominant

Willingness to pay threshold: If value £0/additional vocational recovery, 76%

149 Schizophrenia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness probability Assertive Fol- low-up more cost-effective than standard care. If value £0/1-point improvement on MANSA, 92% probability more cost- effective. Barton et al. 77 young Intervention: Time Use PP: (2009) & people (age Cognitive Be- Survey: Healthcare Fowler et al. 18-52 years) in havioral Structured ac- and Social (2009) early psycho- Therapy tivity Services sis who were (CBT)-Based I: 40.0 (22.8) Improving unemployed Social Recov- C: 34.4 (20.6) ICER (per Social Recov- or underem- ery program QALY): ery in Psycho- ployed in UK. combining d: .258 £200718,844 sis (ISREP) Includes CBT tech- using Cogni- Schizophre- niques with Constructive Willingness to tive Behavior- nia, Schizoaf- vocational economic activ- pay threshold: al Therapy fective Disor- case manage- ity If value is der, Bipolar ment for up to I: 19.2 (21.0) £20K/QALY, Disorder, and 25 sessions C: 15.6 (15.9) 54.3% proba- Psychotic De- over 9 bility Cogni- pression. months. d: .195 tive- 71.4% male. Behavioral 35 in interven- Control: Positive and Therapy- tion, 42 in Vocational Negative Based Social control. case manage- Syndrome Recovery ment alone. Scale more cost- (PANSS): effective than Measures: I: 50.5 (9.2) vocational 9 months C: 50.4 (10.1) case management alone. d: .010

No significant differences on any outcome. Healey et al. 41 persons Intervention: Brief Psychi- PP: (1998) & (age 18-65 Compliance atric Rating Healthcare Kemp et al. years) with Therapy to Scale (BPRS): and Social (1998) psychosis improve I: 12.5 (5.6) Services

150 Schizophrenia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness admitted as compliance C: 14.8 (4.1) Compliance inpatients in for antipsy- Weekly Costs:

Therapy for UK, majority chotic medica- d: .474 I: £1996175 (148) psychosis with Schizo- tion, based on C: £1996193 phrenia, Motivational Global As- (222) Schizoaffec- Interviewing sessment of (NS) tive Disorder, and cognitive Functioning and affective approaches. (GAF): Cost-benefit disorders with I: 62.8 (18.4) between 1-6 psychotic fea- Control: C: 48.3 (14.5) months but not tures. 23 in Non-specific d: .881 after 6 months intervention, counseling. based on com- 18 in control. pliance and in- Measures: sights. 18 months after discharge Kuipers et al. 47 persons Intervention: Brief Psychi- PP: (1998) with medica- Standard care atric Rating Healthcare tion-resistant plus Cogni- Scale (BPRS): and Social Cognitive Be- psychosis, in- tive Behavior- I: 26.35 (6.87) Services havioral cluding diag- al Therapy for C: 23.96 (7.21) Therapy for noses of 9 months. Av- Total Costs persons with Schizophre- erage cost d: .339 (per month): medication- nia, Delusion £1996123/mont Accommoda- resistant psy- Disorder, and h. Percent Clini- tion chosis Schizoaffec- cal Change I: £1996697 (193) tive Disorder Control: (5+ point dif- C: £1996727 in UK. 23 in Standard care ference on (191) intervention, alone. BPRS): 24 in control. I: 65% Service use

Measures: C: 17% I: £1996524 (738) 18 months C: £1996676 (858)

Care package

I: £19961,220 (736)

C: £19961,403 (887)

No significant difference in any costs but size of sample prevents statistical confidence.

151 Schizophrenia

Schizophrenic Spectrum Disorders A prior review of cost-effectiveness for both pharmacological and psychosocial interventions for Schizophrenic Spectrum Disorders identified Compliance Ther- apy and Family Interventions as cost-effective psychosocial approaches (Knapp, 2000). As reviewed in the prior section for psychosis, Compliance Therapy was cost-effective compared to non-specific counseling for a short duration but the effects did not persist after 6 months (Healey et al., 1998; Kemp et al., 1998). The psychosocial interventions below focus on specific symptoms (psychosis, hallucinations, cognitive difficulties). Most studied treatment for Schizophrenic Spec- trum Disorders generally, but one studied treatment for Schizophrenic Spectrum Disorders co-occurring with substance dependence or misuse.

As with the psychosis studies in Denmark reviewed earlier, one study targeted first episode psychosis in persons with Schizophrenic Spectrum. An intensive early intervention program including enriched Assertive Community Treatment, Family Psychoeducation, Social Skills Training, and low-dose medication for two years was more cost-effective than standard community care after five years. The program had clinically significant benefits at the end of treatment at two years, but those differences did not persist at five years. Nonetheless, since there were no significant cost differences, there was more than 95% likelihood that the program was cost-effective per incremental improvements in functioning (Global Assessment of Functioning; Hastrup et al., 2013). The duration of this study is especially noteworthy in that it demonstrates the long-term economic benefits of a time- and resource-intensive intervention.

The addition of Cognitive Behavioral Therapy to usual care appeared to be cost- effective for patients with Schizophrenic Spectrum Disorders. For patients enter- ing inpatient care for an acute psychosis episode in the United Kingdom, adding CBT to usual inpatient treatment led to greater improvements in negative symptoms and social functioning compared to usual treatment alone after two years with no significant differences in total service costs (Startup et al., 2005). Togeth- er these two studies suggest adding CBT to care may be cost-effective. For patients with persistent or recurrent psychotic symptoms in the Netherlands— similar to the medication-resistant psychosis reviewed earlier—adding CBT to standard care cost €47 per additional day of normal functioning after 18 months; therefore, cost-effectiveness depends on the willingness to pay threshold. If the value was €84 per additional day of normal functioning, then there was a 70% likelihood that the addition of CBT was cost-effective (van der Gaag et al., 2011).

For persistent auditory hallucinations despite adequate treatment in persons with Schizophrenia in the Netherlands, customized Hallucination-Focused Inte- grative Therapy (HIT) including CBT, coping training, and psychoeducation was not cost-effective over usual care. However, this treatment has potential to be cost-effective as there was a trend toward cost-savings with better clinical outcomes and fewer costs at $936 saved per incremental improvement on a measure of psychopathology (Positive and Negative Syndrome Scale) after 18 months (Stant et al., 2003; Jenner et al., 2006).

152 Schizophrenia

For cognitive and social difficulties in persons with Schizophrenia in the United Kingdom, the addition of Cognitive Remediation Therapy to usual care to target cognitive flexibility, working memory, and planning did improve working memory (39% versus 15%), but it was not considered cost-effective per incremental improvement in working memory over the longer term. Although there was an 80% probability that the additional Cognitive Remediation Therapy was more cost-effective than usual care alone at 14 weeks, there was only a 20% probability after the full 40 weeks. The researchers note that this is likely due to the smaller cost advantage at the second time point (Patel et al., 2010; Wykes et al., 2007).

Only one study targeted Schizophrenia without a focus on specific symptoms. In the United Kingdom, Group Art Therapy added to standard care was not cost- effective compared to either generic group activity sessions or standard care alone, with less than 50% likelihood of being more cost-effective at any willingness to pay threshold after two years. Notably, attendance was quite low, with 39% of persons assigned to Group Art Therapy and 48% of persons assigned to generic group activity sessions never attending a single session (Crawford et al., 2012). Even if the intervention were cost-effective, acceptability and adherence might be low. Further studies may be able to refine what kind of patients chose to attend regularly, and if the intervention may be cost-effective for that subset.

Finally, only one study targeted persons with Schizophrenic Spectrum Disorders and co-occurring substance dependence or misuse. In the United Kingdom, the addition of an integrated treatment including individual CBT and a motivational intervention for substance use and Family Therapy for caregivers was likely to be more cost-effective than routine care alone with significant improvements in global functioning and negative symptoms with no significant difference in associated costs after 18 months (Haddock et al., 2003). Interestingly, two CBT-based treatments observed that improvements in positive symptoms up to 12 months did not persist after 18 to 24 months, while improvements in negative symptoms did persist at those time points (Startup et al., 2005; Haddock et al., 2003).

Table 2. Behavioral Interventions for Schizophrenic Spectrum Disorders Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Hastrup et al. 301 persons Intervention: Global As- PP: Public (2013) (age 18-45 Intensive ear- sessment of Sector years) with a ly interven- Functioning Early inter- Schizophrenic tion program (GAF): Total Costs: vention for Spectrum with enriched Two years I: €2009123,683 first episode Disorder and Assertive I: 55.16 (15.15) (SE 8,970) psychosis in first episode Community C: 51.13 C: €2009148,651 Schizophrenic psychosis in Treatment, (15.92) (SE 13,073) Spectrum Denmark. 151 Family Psy- Disorder in interven- choeducation, d: .259 Willingness to (OPUS Study) tion, 150 in Social Skills pay threshold: control. Training, and Five years Even if value low-dose I: 55.35 (18.28) is €0/1-point

153 Schizophrenia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness medication for C: 54.16 improvement 2 years. (18.41) in GAF, 95.3% (NS) probability Control: intensive pro- Standard d: .065 gram more community cost-effective treatment. Clinically sig- than standard nificant differ- community Measures: ences at end-of- treatment. If 5 years treatment (two value is years). €2K/1-point improvement in GAF, probability increases to 96.5%. Crawford et 286 persons Intervention: Global As- PP: Societal al. (2012) (age 18+ Standard care sessment of years) with plus Group Functioning ICER (per Group Art Schizophrenia Art Therapy Scale (GAF): QALY): Therapy for in UK. 67% in up to 8- I: 45.6 (13.1) I vs. C1

Schizophrenia male. 96 in person groups C1: 46.4 (13.6) £2008303,793 (MATISSE intervention, for weekly 90- C2: 46.8 (12.8) Study) 100 in control minute ses- (NS) I vs. C2

#1, 90 in con- sions over 12 £200828,105 trol #2. months. Av- d1: .060 erage cost d2: .093 ICER (per 1-

£2008641/patie point im- nt. provement in Positive and GAF): Controls: Negative I vs. C1

(1) Standard Syndrome £200815,944 care plus Scale group activity (PANSS): I vs. C2

sessions for I: 69.2 (21.8) £20081,011 weekly 90- C1: 66.9 (23.3) minute ses- C2: 68.1 (20.7) Willingness to sions over 12 (NS) pay threshold: months. For any val- (2) Standard d1: -.102 ue/QALY, care alone. d2: -.052 ≤50% probability Group Measures: No significant Art Therapy 24 months differences on more cost- any measure. effective than standard care

154 Schizophrenia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness or group activity sessions. If value up to £10K/1-point improvement in GAF, 50- 67% probability more cost- effective. van der Gaag 216 persons Intervention: Positive and PP: Societal et al. (2011) (age 16-64 Cognitive Be- Negative years) with havioral Syndrome ICER (per day Cognitive Be- Schizophrenia Therapy for Scale of normal havior Thera- or Schizoaf- 26 weekly ses- (PANSS): functioning py for persis- fective Disor- sions, but I: 61.2 (SE 1.5) gained): tent and recur der with per- could end ear- C: 62.7 (SE €200747 rent psychosis sistent and lier if partici- 1.6) Willingness to in Schizo- recurrent psy- pant achieved (NS) pay threshold: phrenic Spec- chosis in the goals set. If value trum Disorder Netherlands. d: .095 €84/additiona 109 in inter- Control: l day of nor- vention, 97 in Treatment as Psychotic mal function- control. usual. Symptoms ing gained, Rating Scale 70% probabil- Measures: (PSYRATS): ity Cognitive 18-month fol- I: 19.9 (SE 1.6) Behavioral low-up C: 27.8 (SE Therapy more 1.8) cost-effective (p=.04) than treat- d: .459 ment as usual.

Number of Days Func- tioning With- in Normal Range: I: 183 C: 106 Patel et al. 67 partici- Intervention: Positive and PP: Societal (2010) & pants with Usual care Negative Wykes et al. Schizophrenia plus Cogni- Syndrome Total Costs:

(2007) and cognitive tive Remedia- Scale I: £200116,338 and social tion Therapy (PANSS): (11,362)

Cognitive functioning for 40 sessions I: 61.3 (20.1) C: £200115,338 Remediation difficulties in at least 3x/ C: 56.2 (13.6) (12,001) Therapy in UK. 73% weekly target-

155 Schizophrenia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Schizophrenia male. 34 in ing cognitive d: .303 Given signifi- intervention, flexibility, cant clinical 33 in control. working Digit Span – improvement memory, and Wechsler without addi- planning. Av- Adult Intelli- tional costs, no erage cost gence Scale-III ICERs were £631.90/patie (WAIS-III): calculated. nt. I: 15.1 (3.7) C: 14.6 (4.1) Willingness to Control: pay threshold: Usual care. d: .128 If value is £1,950/1- Measures: percent with 40-week fol- Percent with improved low-up Improved working Working memory, max- Memory (≥2 imum 20% improvement probability on WAIS-III): Cognitive I: 39% Remediation C: 15% Therapy more cost-effective than usual care. If value is £5K, still only 30% cost- effective. Startup et al. 90 patients Intervention: Least square PP: (2005) (age 18-65 Treatment as means Healthcare years) with a usual plus Cognitive Be- Schizophrenic Cognitive Be- Scale for As- Total Direct havioral Spectrum havioral sessment of Service Costs:

Therapy for Disorder re- Therapy in Positive I: £200127,535 acute Schizo- cently admit- weekly meet- Symptoms: (17,705) phrenic Spec- ted to psychi- ings. Average I: 3.39 (SE .55) C: £200127,956 trum Disor- atric hospital cost £2001769/ C: 4.37 (SE (19,716) ders for acute psy- patient. .57) (NS) chotic episode in UK. 47 in Control: Scale for As- intervention, Treatment as sessment of 43 in control. usual. Negative 73% at 2 Symptoms: years. Measures: I: 4.32 (SE .65) 24 months C: 7.09 (SE .67) (p=.004)

156 Schizophrenia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness

Social Func- tioning Scale: I: 104.00 (SE 1.63) C: 97.81 (SE 1.66) (p=.009)

Global As- sessment of Functioning: I: 56.2 (SE 2.57) C: 49.17 (SE 2.64) Haddock et al. 36 patients Intervention: Global As- PP: Societal (2003) (age 18-65 Individual sessment of years) with and family- Functioning Total Costs:

Cognitive Be- Schizophrenic oriented Cog- Scale (GAF): I: £1998-19998,753 havioral Spectrum nitive Behav- I: 60.12 (18.96) (4,804)

Therapy and Disorder and ioral Therapy C: 53.44 C: £1998- motivational comorbid program plus (13.00) 199910,013 intervention substance de- motivational (p=.048) (10,717) for Schizo- pendence or intervention (NS) phrenia and misuse and for substance d: .418 substance their carers in use problems No significant misuse UK. 18 in infor 9 months. Positive and difference in tervention, 18 Individual in- Negative cost outcomes. in control. tervention for Syndrome approx. 29 Scale ICER (per 1- sessions, fami- (PANSS): point im- ly interven- Positive provement in tion 10-16 ses- I: 13.87 (4.27) GAF) sions. C: 12.93 (4.23) (NS) Willingness to Control: pay threshold: Routine care. d: .221 If value £0/1- point im- Measures: Negative provement in 18 months I: 10.27 (2.25) GAF, 69.3% C: 15.5 (5.71) probability (p=.004) integrated intervention d: 1.314 more cost- effective than

157 Schizophrenia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Total routine care; if I: 52.50 (11.12) value £20, C: 58.50 70% probabil- (15.04) ity more cost- (NS) effective; if value £655, d: .459 90% probability more cost- Trends toward effective. improvement but no significant difference in carer outcomes after 12 months so not included here. Stant et al. 63 patients Intervention: Positive and PP: Societal (2003) & Jen- with Schizo- Hallucination- Negative ner et al. phrenia and Focused Inte- Syndrome ICER (per 1- (2006) persistent au- grative Ther- Scale point im- ditory hallu- apy, combin- (PANSS): provement in Hallucination- cinations de- ing Cognitive I: 51.5 (15.8) PANSS):

Focused Inte- spite adequate Behavioral C: 57.3 (17.4) −$2000936 grative Ther- treatment for Therapy, cop- (NS) apy for pa- 2+ years in the ing training, No significant tients with Netherlands. psychoeduca- d: .349 differences in Schizophrenia 31 in intervention, motiva- clinical out- and persistent tion, 32 in tional inter- comes or total auditory hal- control. ventions, re- costs, but trend lucinations habilitation, toward lower and medica- mean costs and tion for 9 improvement in months. Av- PANSS scores erage cost suggests cost-

$20001,698/pati effectiveness. ent.

Control: Usual care.

Measures: 18 months

158 Schizophrenia

LIMITATIONS AND FUTURE DIRECTIONS As expected, the biggest limitation is the lack of sufficient cost-effectiveness studies to draw meaningful conclusions. Most studies compared psychosocial interventions to usual care but not to each other. However, it would be valuable to know, for example, if Cognitive Behavioral Therapy were more or less cost- effective than Family Therapy. Overall, a major barrier to developing cost- effectiveness recommendations for Schizophrenic Spectrum Disorders in general is the relatively limited data available. One possible reason for under- representation of this population is that persons with severe neuropsychiatric illnesses are unable to engage successfully with health systems. Further, they may be exceptionally difficult to recruit and retain in clinical trials. This has implications for the types of persons who get enrolled into and complete these studies and creates challenges for conducting trials with patients that are representative of the population at large.

More data are needed not only for the different disorder subtypes (e.g., Schizoaf- fective Disorder) but also for the different types of symptoms (positive, negative, cognitive). Clearly, targeting first-time or early psychosis is one critical juncture for treatment. However, different types of psychosis may benefit from different types of interventions; for example, one study indicated the potential cost- effectiveness of a hallucination-specific intervention. Additional research on cost- effective interventions for hallucinations, delusions, thought disorders, and movement disorders would be informative. Similarly, one study indicated the potential cost-effectiveness of a cognitive intervention, and cost-effective solutions for cognitive difficulties remain another avenue for additional research.

It is likely that behavioral treatments to improve general functioning during maintenance phases of these persistent chronic illnesses will also have long-term economic benefit. Psychosocial interventions may be able to alleviate some of the typical negative emotions and behaviors like self-neglect and lack of pleasure that can accompany these disorders, as these symptoms can occur and have been targeted in other neuropsychiatric disorders as well. Finally, given the severe impairments on life functioning, a few studies looked at the impact of these psychosocial interventions on returning to work (i.e. vocational recovery). However, further studies may be able to utilize other payer perspectives to incorporate the indirect costs such as lost productivity. These will help inform more accurate analyses of the overall cost-effectiveness of these types of interventions.

Schizophrenic Spectrum Disorders are particularly complex neuropsychiatric disorders, so much so that treatment recommendations center on tailoring the treatment to the individual patient’s needs. With this heterogeneity of experiences, it is unsurprising that many interventions work to target a specific subset of symptoms (e.g., psychosis, hallucinations). Yet another possibility to consider is interventions that may be able to target multiple symptoms simultaneously, or even preventively. Overall, the most cost-effective options may vary for different sub-populations, and further refinement of our understanding about which options are effective for which symptoms will not only optimize care but also reduce costs as more targeted treatment options become available.

159 Schizophrenia

KEY POINTS • Further studies are needed to replicate results found in single studies before cost-effectiveness conclusions can be made more definitively.

• For first and early episodes of psychosis, psychosocial interventions consistently appeared to be cost-effective additions to standard care. o Assertive Follow-Up from a multidisciplinary team dominated standard care for both quality of life and return to work after 18 months. o Cognitive Behavioral Therapy (CBT)-Based Social Recovery combining CBT and vocational case management for persons who were unemployed or underemployed had more than 50% likelihood of being more cost- effective than vocational case management alone. o An intensive intervention with Assertive Community Treatment, Family Psychoeducation, and Social Skills Training delivered for two years was more cost-effective than standard community care after five years.

• For acute, persistent, and medication-resistant psychosis, Cognitive Behav- ioral Therapy appeared to be more cost-effective than standard care alone. o For acute psychosis in inpatient care, the addition of CBT to standard care improved clinical outcomes without any additional costs relative to standard care alone after two years, which suggests cost-effectiveness. o For persistent and recurrent psychosis, the addition of CBT to standard care may be cost effective, depending on the willingness to pay threshold. o For medication-resistant psychosis, the addition of CBT to standard care improved clinical outcomes without any additional costs relative to standard care alone after 18 months. This suggests cost-effectiveness.

• For acute psychosis in inpatient care, Compliance Therapy to improve medication adherence via Motivational Interviewing and cognitive approaches appeared to be more cost-effective than non-specific counseling during the first 6 months but the effects were not sustained after 6 months.

• For persistent auditory hallucinations despite adequate treatment for at least two years, a customized Hallucination-Focused Integrative Therapy including Cognitive Behavioral Therapy, coping training, and psychoeducation had a trend toward being more cost-effective than usual care after 18 months.

• For cognitive and social difficulties, Cognitive Remediation Therapy to target cognitive flexibility, working memory, and planning might be cost-effective after 14 weeks but was not more cost-effective than usual care after 40 weeks.

• For general treatment, Group Art Therapy was not cost-effective compared to either general activity group sessions or standard care, with less than 50% likelihood of being more cost-effective at any willingness to pay threshold after two years. Additionally, adherence to even a single session was low.

160 Schizophrenia

• For Schizophrenic Spectrum Disorders and co-occurring substance misuse, an integrated treatment including Cognitive Behavioral Therapy and a motivational intervention for substance use and Family Therapy for caregivers had clinical improvements without any significant differences in costs relative to standard care after 18 months. This suggests cost-effectiveness.

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162 Schizophrenia van der Gaag M, Stant AD, Wolters KJ, Buskens E, Wiersma D. Cognitive- behavioural therapy for persistent and recurrent psychosis in people with schizophrenia-spectrum disorder: cost-effectiveness analysis. Br J Psychiatry. 2011 Jan;198(1):59-65, sup 1.

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163 Personality Disorders

CHAPTER 5: PERSONALITY DISORDERS

ABSTRACT A personality disorder consists of a long-lasting pattern of inflexible and pervasive thoughts and behaviors that the individual may think are normal but that deviate from social norms, cause distress, and impair functioning. There are ten types of personality disorders: Antisocial, Avoidant, Borderline, Dependent, His- trionic, Narcissistic, Obsessive-Compulsive, Paranoid, Schizoid, and Schizotypal.

Borderline Personality Disorder is considered the most common personality disorder, and thus the one with the most information available. In the United States, lifetime prevalence of at least one personality disorder is estimated at 9.1% to 14.8%. Additionally, for persons who do not meet an official diagnosis, lifetime prevalence of Personality Disorder Not Otherwise Specified (PDNOS) is estimated at 8% to 13%. Data on the economic burden of personality disorders in the United States is unavailable. In England, the total direct and indirect costs from personality disorders were estimated at £7.9 billion annually. Across 30 countries in Europe, the total direct and indirect costs were estimated at €27.3 billion annually, with 78% from indirect costs.

Treatment guidelines for most personality disorders have not been established. Psychotherapy is first-line treatment, while pharmacotherapy may be used to target specific symptoms, but has not been approved for primary treatment. Lim- ited data on cost-effectiveness exists, with no cost-effectiveness trials in the U.S. population to date. Moreover, the lack of established willingness to pay thresholds for the measures used prevents conclusions around overall cost- effectiveness. In comparing inpatient and outpatient delivery modalities for unspecified or multiple personality disorders, lower-intensity outpatient programs appeared more cost-effective than higher-intensity inpatient ones, although cost- effectiveness relative to routine psychiatric services will depend on the willingness to pay threshold. For Borderline Personality Disorder, the addition of Cog- nitive Behavioral Therapy had the potential to be more cost-effective than usual care alone after six years, and Schema-Focused Therapy dominated Transfer- ence-Focused Psychotherapy after four years, although no comparison was made to usual care. For personality-disordered patients who self-harm, neither Dialec- tical Behavior Therapy nor a joint crisis plan written in collaboration with service providers for treatment preference had any clinical or cost differences compared to usual care.

Overall, more data are needed to draw meaningful conclusions about the cost- effectiveness of behavioral interventions for personality disorders in general and any of the ten specific types in particular.

BACKGROUND ON DISORDER Personality disorders are a class of neuropsychiatric disorders characterized by a long-lasting pattern of inflexible and pervasive thoughts and behaviors that deviate from social norms and can cause significant distress across all domains of life including interpersonal relationships and work. Notably, people with per-

164 Personality Disorders sonality disorders often think their distorted thoughts and behaviors are appropriate and normal, and they may not desire to change themselves (NIMH, 2014).

In addition to these general characteristics, there are ten unique personality disorders outlined in the most recent version of the American Psychiatric Associa- tion’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5). A proposed update recommends a shift to focus more on personality traits than categorical diagnoses, but the current manual retains the following classifications:

• Antisocial Personality Disorder is characterized by disregard for right or wrong, including lack of empathy, lack of remorse, persistent lying or deceit to exploit others, risk-taking behaviors, disregard for safety of self or others, irritability, aggressiveness, impulsivity, and irresponsibility.

• Avoidant Personality Disorder is characterized by an inability to stop thinking about one’s own shortcomings and a pattern of feeling shy and inade- quate. It can include sensitivity to rejection, reluctance to become involved with people, and avoidance of activities or jobs that involve others.

• Borderline Personality Disorder is characterized by problems with regulating emotions and thoughts, impulsive and reckless behaviors, and unstable relationships. It can include extreme reactions to real or perceived abandonment, a distorted and unstable sense of self, intense and highly changeable moods, and stress-related paranoid thoughts. Note that self-harm behaviors are one of the potential diagnostic criteria for Borderline Personality Disorder.

• Dependent Personality Disorder is characterized by an over-dependence on others to meet emotional and physical needs, including distrust in one’s own ability to make decisions and becoming very upset by separation and loss. It can include avoidance of being alone, avoidance of personal responsibility, and becoming easily hurt by criticism and disapproval.

• Histrionic Personality Disorder is characterized by attention-seeking behaviors, including being overly seductive, easily influenced by others, overly concerned with looks, overly dramatic and emotional, overly sensitive to criticism or disapproval, blaming failure or disappointment on others, constantly seeking reassurance or approval, and quickly changing emotions.

• Obsessive-Compulsive Personality Disorder is characterized by a preoccupation with rules, orderliness, and control, including over-devotion to work, lack of flexibility, lack of generosity, unwillingness to show affection, and preventing others from actions. Unlike Obsessive-Compulsive Disorder where thoughts are unwanted (see Chapter 2 on Anxiety Disorders), in the case of Obsessive Compulsive Personality Disorder the thoughts are believed to be correct.

165 Personality Disorders

• Narcissistic Personality Disorder is characterized by an excessive sense of self-importance, extreme preoccupation with self, and lack of empathy for others. It can include strong reactions to criticism, taking advantage of others to achieve goals, exaggerating achievements and talents, needing constant attention and admiration, and disregarding the feelings of others.

• Paranoid Personality Disorder is characterized by a persistent pattern of distrust and suspicion of others, including concerns about the hidden motives of others, expectation of exploitation by others, inability to work with others, social isolation, detachment, and hostility.

• Schizoid Personality Disorder is characterized by social isolation and a pattern of indifference to others, including a lack of emotional expression, appearing aloof and detached, avoiding social activities that involve emotional intimacy with others, and not wanting or enjoying close relationships. It is the mildest disorder in the schizophrenic spectrum of disorders (see Chapter 4), as it does not include paranoia or hallucinations.

• Schizotypal Personality Disorder is also characterized by limited interactions with others, in part due to others impressions of the person as being odd and eccentric and in part due to the individual’s limited understanding on how relationships form or how behaviors impact others. It can include a lack of emotional expression, distrust and suspicion of others, high social anxiety, inappropriate responses to social cues, and peculiar beliefs and behaviors. It is also part of the schizophrenic spectrum of disorders (see Chapter 4).

Notably, Personality Disorders are less commonly diagnosed and treated in the United States, so most data to date come from other regions. There is a strong bias for researching Borderline Personality Disorder, which many consider the most common and most treatable of the personality disorders, with the remainder of personality disorders understudied or unspecified when studied.

PREVALENCE OF DISORDER In the United States, two nationally representative studies found lifetime prevalence rates ranging from 9.1% to 14.8% (30.8 million people) for at least one personality disorder, the latter estimate limited to seven of the ten personality disorders (Lenzenweger et al., 2007; Grant et al., 2004). Lifetime prevalence for the specific disorders were estimated at 7.88% for Obsessive-Compulsive Personality Disorder, 5.9% for Borderline Personality Disorder, 4.41% for Paranoid Personali- ty Disorder, 3.63% for Antisocial Personality Disorder, 3.13% for Schizoid Per- sonality Disorder, 2.36% for Avoidant Personality Disorder, 1.84% for Histrionic Personality Disorder, and 0.49% for Dependent Personality Disorder. Estimates for Narcissistic Personality Disorder and Schizotypal Personality Disorder are currently unavailable (Grant et al., 2004; Grant et al., 2008).

Like many neuropsychiatric disorders, not all persons with disordered symptoms meet criteria for a categorical diagnosis. A meta-analysis of over 100 studies including Personality Disorder Not Otherwise Specified (PDNOS) estimated life-

166 Personality Disorders time prevalence in the range of 8% to 13%, noting it may be the third most common diagnosis after Borderline Personality Disorder and Avoidant Personality Disorder (Verheul & Widiger, 2004). This may explain in part why a sizeable number of studies do not limit their findings to a single personality disorder. However, it may also lead to underestimates for prevalence and economic burden if persons with these disordered symptoms are not accounted for in calculations.

Personality disorders are significant predictors of disability (Grant et al., 2004; Grant et al., 2008), and a global meta-analysis suggests four times the risk of mortality (Eaton et al., 2008). In most cases, personality disorders are highly comorbid with each other and with other neuropsychiatric disorders. For instance, Borderline Personality Disorder has a high co-occurrence with other neuropsychiatric disorders (84.5%), including mood (29.4%), anxiety (21.5%), and substance use (14.7%) disorders, as well as substantial physical and mental disability. Among other things, Borderline Personality Disorder is associated with severe functional impairment, substantial treatment utilization, and a high rate of mortality by suicide (Lenzenweger et al., 2007; Grant et al., 2008).

ECONOMIC BURDEN OF DISORDER One in ten people are estimated to have at least one personality disorder in their lifetime, yet no representative studies have estimated the economic burden of personality disorders in the United States. A global meta-analysis also found limited economic data, with one study from the Netherlands estimating the health and social costs of treatment at £11,126 per patient in the year prior to treatment, of which 66.5% were due to direct medical costs, and the remainder were due to productivity losses (Soeteman et al., 2008). Based on this, it was estimated that if every American with the disorder were to receive treatment, it would cost $446 billion annually; however, data are unavailable on the number of people who need, would participate in, or would benefit from treatment (Eaton et al., 2008).

Data from comparable countries like England estimated direct health and social service costs due to personality disorders at £704 million annually. When indirect costs (i.e. productivity losses) were included, it brought the estimates up to £7.9 billion annually as of 2007. Further, the costs were projected to reach £1.1 billion in direct costs and £12.3 billion in combined direct and indirect costs by 2026 (McCrone et al., 2008). Both of the above estimates rely on data from persons who were in contact with services, and not those unknown to services, in contact but with a different diagnosis, or opting to reject treatment (Tyrer et al., 2010). Finally, estimates across 30 European countries was estimated at €27.3 billion annually, with 78% from indirect costs as of 2010 (Olesen et al., 2012). Clearly, personality disorders impart a large economic burden on the healthcare system and society at large.

CLINICALLY EFFECTIVE INTERVENTIONS Specific treatment guidelines for most personality disorders do not exist; however, psychotherapy is always first-line treatment. Pharmacotherapy is not approved for any personality disorders, although psychiatric medications may be used to target specific symptoms. In some cases, personality disorders do require

167 Personality Disorders psychiatric hospitalization if persons are a threat or danger to themselves or others or unable to take care of themselves. After stabilization, they may transition to a residential program, day program, or outpatient treatment. Notably, much of the existing cost-effectiveness research specifically compares these different types of delivery mechanisms. Interestingly, in cases where persons with personality disorders do not want their personalities to change, modifying the environment rather than their personality may be another avenue of research (Tyrer et al., 2010).

Borderline Personality Disorder is one the few personality disorders with treatment guidelines. As with personality disorders in general, the primary treatment recommendation is for psychotherapy, with adjunctive pharmacotherapy to target symptoms if helpful. Multiple psychotherapies have demonstrated clinical effectiveness for Borderline Personality Disorder, including Dialectical Behavior- al Therapy (DBT), Comprehensive Validation Therapy (CVT), and psychoanalytic/psychodynamic therapy. Cognitive Behavioral Therapy (CBT) may also be effective. At time of writing, cost-effectiveness trials for CVT and psychoanalytic/psychodynamic therapy were not available.

CBT is a common psychotherapy across neuropsychiatric disorders; It involves learning how to target and modify thoughts, feelings, and behaviors that lead to distorted beliefs and self-destructive actions. Personality disorders in particular include extreme and inflexible patterns of thinking that may benefit from CBT; however, it may also require overcoming treatment resistance from patients who think their disordered thoughts, feelings, and behaviors are normal and acceptable and do not require modification.

DBT is a popular psychotherapy for personality disorders, and is considered the gold standard treatment for Borderline Personality Disorder. Building on CBT, the core tenet is acceptance of thoughts, feelings and behaviors, even if they are uncomfortable or undesired, while acknowledging the need for change. This includes validation, training on mindfulness and other relaxation techniques, supportive therapy, and development of coping skills. DBT combines individual therapy, group skills training, and team support for therapists to build skills to regulate emotions, tolerate distress, and facilitate interpersonal relationships.

One cost-effectiveness study compared Schema-Focused Therapy and Transfer- ence-Based Psychotherapy. Schema-Focused Therapy specifically targets lifelong, self-defeating thought patterns known as schema. There are 18 enumerated schemas, focused primarily on early maladaptive and dysfunctional patterns regarding the self and others. Transference-Based Psychotherapy is a psychodynamic therapy created for Borderline Personality Disorder. Like all of the treatments discussed thus far, the goal is to correct distorted thoughts; in this case, the target is the patient’s perception of significant others and of the therapist.

COST-EFFECTIVENESS OF INTERVENTIONS In addition to the lack of U.S. studies, just over half of available studies do not limit their interventions to a single type of personality disorder (although some have exclusion criteria for specific types such as schizotypal and antisocial). Fur-

168 Personality Disorders ther, no societal value has been assigned for acceptable costs per improvement on personality-disorder-related outcomes, which would be needed to standardize willingness to pay thresholds. In short, limited data are available to draw any meaningful conclusions about the cost-effectiveness of behavioral interventions for personality disorders in the United States or elsewhere.

A review of cost-effective interventions for Borderline Personality Disorder noted that psychotherapy’s clinical efficacy was more promising than its cost- effectiveness but that there was a high level of uncertainty in the findings. Based on included trials, Manual-Assisted Cognitive Behavioral Therapy was unlikely to be cost-effective, Dialectical Behavior Therapy had the potential to be cost- effective but current data did not support that conclusion, and Mentalization- Based Partial Hospitalization might be cost-effective (Brazier et al., 2006).

Unspecified or Multiple Personality Disorders In studies that do not specify a single personality disorder, most focus on the way treatment is delivered rather than the type of treatment itself; in particular, comparing between specialist versus generalist care, or inpatient versus outpatient treatments, or studying aftercare programming. Since specialist and inpatient treatments are typically more resource intensive and expensive while general and outpatient treatments are relatively less intensive and expensive, it is useful to compare cost-effectiveness between them.

For example, a longer specialist inpatient treatment for 11-16 months (One-Stage program) and a shorter specialist inpatient treatment for 6 months followed by community-based therapeutic support for 12-18 months (Step-Down program; longer treatment period overall) were compared to routinely available psychiatric services in the United Kingdom. Due to geographical limitations, participants were non-randomly allocated to treatment depending on proximity to outpatient services. Both treatment programs were more clinically effective and more expensive than routine services after a year. However, while they were similarly costly, Step-Down was more clinically effective than One-Stage. Given this, cost- effectiveness analyses compared Step-Down to routine services, with incremental cost per incremental improvement on all measures exceeding £1,000 (£1,231 per incremental improvement for Positive Symptoms, £3,405 for Global Assessment Scale, £30,304 for General Severity Index) after 18 months (Beecham et al., 2006). Cost-effectiveness will depend on the willingness to pay threshold.

In Norway, a similar comparison was made between inpatient treatment followed by outpatient treatment and outpatient treatment alone. In this case, inpatient step-down treatment entailed day-hospital-based group psychoanalytic and cognitive behavioral therapies for 18 weeks, followed by outpatient individual and group therapy for two-and-a-half years and only group therapy for the final year. The outpatient treatment alone consisted of individual psychotherapy without limit to intensity, duration, or other services. After three years, there were no significant differences in total costs, but outpatient treatment was more clinically effective than inpatient step-down treatment, suggesting the inpatient treatment cost approximately €22 per incremental decrease on a measure of functioning (Global Assessment of Functioning) compared to outpatient treatment.

169 Personality Disorders

Further analyses suggested these differences were limited to patients with Avoidant Personality Disorder (40% of total), who has significantly greater improvements but also significantly greater costs. For Borderline Personality Disor- der (46% of total), there were no significant differences in improvements or costs (Kvarstein et al., 2013). This highlights the importance of specific studies for each disorder type.

After completion of a three-month inpatient program, cost-effectiveness of two different aftercare interventions to sustain treatment effects was compared in the Netherlands. Usual aftercare of two booster sessions at three and nine months dominated a specialized reintegration program of six monthly three-hour sessions in terms of total intervention costs after 24 months. Notably, the usual care booster sessions also had significantly higher participation than the reintegration program, with average attendance of 83.6% versus 64.6% (Thunnissen et al., 2008). This suggests it is also the more acceptable option.

Finally, Dialectical Behavior Therapy (DBT) with weekly therapy, group skills training, and phone-based coaching for patients with personality disorders and more than five days of self-harm in the prior year in the United Kingdom had the potential to be more cost-effective than treatment as usual (includes psychotherapy other than DBT), depending on the willingness to pay threshold, at £36 per incremental improvement in self-harm per two-month period after 12 months. Notably, only 48% of participants completed the program. The program produced no significant differences in clinical outcomes or total service costs (Priebe et al., 2012).

Table 1. Behavioral Interventions for Unspecified or Multiple Personality Disorders Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Kvarstein et 107 patients Intervention: Global As- PP: al. (2013) with personal- Day-hospital- sessment of Healthcare ity disorders based step- Functioning Inpatient day- in Norway. down treat- (GAF): Total Costs: hospital-based 40% Avoidant ment program I: 57 (12) I: €200631,823 step-down Personality combining in- C: 67 (13) (SE 479) treatment vs. Disorder, 46% dividual and (p<.05) C: €200631,607 outpatient Borderline group psycho- Higher is bet- (SE 956) treatment for Personality therapy for ter. personality Disorder. 75% max. 4 years. Avoidant PD disorders female. 56 in d: -.800 I: €200635,524 intervention, Control: (SE 381)

51 in control. Outpatient Change in GAF C: €200649,728 individual I: 10 (SE .3) (SE 525) psychothera- C: 18 (SE .1) (p<.05) py at special- (p<.05) ist practice, no Borderline PD

limitations on d: -5.406 I: €200629,709 duration, in- (SE 1,275)

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness

tensity, or Avoidant PD C: €200621,309 other services. I: 6 (SE .5) (SE 2,482) C: 19 (SE .01) Measures: (p<.05) ICER (per 1- 3 years point im- d: -6.819 provement in GAF): Borderline PD All patients

I: 14 (SE .6) -€200622 C: 17 (SE .2) (NS) Avoidant PD

€20061,093 d: -1.014 Borderline PD

-€2006-2,800 Priebe et al. 74 partici- Intervention: Zanarini Rat- PP: (2012) pants with Dialectical ing Scale for Healthcare a personality Behavior Borderline and Social Dialectical disorder and Therapy with Personality Services Behavior 5+ days of weekly 1-hour Disorder Therapy for self-harm in therapy ses- (ZAN-BPD): self-harming the previous sions, weekly I: 13.1 (6.9) Total Service patients with year in UK. 38 1-hour skills C: 15.9 (7.5) Costs: personality in interven- training (NS) I: £5,685 disorders tion, 36 in groups, and (€6,786) control. 48% phone-based d: .389 C: £3,754 completed in- skills coaching (€4,481) tervention. as needed for (NS) 12 months. ICER (per 1- Control: point reduc- Treatment as tion in self- usual. harm per 2- month peri- Measures: od): 12 months £36 Thunnissen et 128 ex- Intervention: Global Severi- PP: Interven- al. (2008) patients (age Reintegration ty Index (GSI): tion 20-53 years) program I: .44 (.40) Reintegration who had aimed at im- C: .40 (.43) Program training pro- completed 3- proving gen- (NS) Costs: gram vs. month inpa- eral function- I: €1,891 booster ses- tient psycho- ing and work d: .096 C: €1,198 sions after therapy for resumption short-term in- personality with 6 month- Percent with Lower costs and patient psy- disorders in ly 3-hour ses- Paid Job: better clinical

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness chotherapy the Nether- sions. Aver- I: 75.9% outcomes for for personali- lands. Often c- age 64.6% par- C: 86.8% usual aftercare ty disorders morbid with ticipation. with booster other neuro- Percent with sessions. Given psychiatric Control: Absence from this, did not disorders Usual after- Work: conduct cost- (e.g., anxiety care of two I: 7.4% effectiveness or depressive one-day C: 11.5% analysis. disorders). booster sessions at 3 and Percent with 9 months with Impediments same thera- at Work: pists as pri- I: 36.1% mary treat- C: 27.8% ment. Aver- age 83.6% participation.

Measures: 24 months Beecham et al. 108 patients Interventions: Change in PP: Societal (2006) (age 18-55 (1) One-Stage Global As- years) with program with sessment Total Costs: Comparing personality 11-16 months Scale (GAS): I1: £58,241 two psycho- disorders in of inpatient I1: 10.44 (12,623) social pro- UK. 32 in in- treatment, in- (12.99) I2: £59,041 grams (One- tervention #1, cluding 2x/ I2: 12.21 (13,172) Stage and 29 in interven- week individ- (14.41) C: £29,002 Step-Down) tion #2, and ual psycho- C: 5.40 (8.92) (10,682) for personali- 47 in control. therapy, ty disorders weekly group d1: .460 Since I2 more psychothera- d2: .584 clinically effec- py, psycho- d3 (I1 vs. I2): tive than I1, all tropic medica- .129 ICER compare tion, and I2 and control. structured ac- Change in tivities. General Se- ICER (per 1- (2) Step-Down verity Index point im- group with 6 (GSI): provement on months of in- I1: .40 (.80) GAS): patient treat- I2: .82 (.89) £3,405 ment as de- C: .01 (.64) scribed above ICER (per 1- followed by d1: .542 point im- and 12-18 d2: 1.059 provement on months of fol- d3 (I1 vs. I2): GSI):

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness low-up outpa- .497 £30,304 tient treatment includ- Change in ICER (per 1- ing 2x/week Positive point im- group analytic Symptom To- provement on psychothera- tal (PST): PST): py, individual I1: 9.09 (18.39) £1,131 and group I2: 23.45 meetings, and (23.11) ICER (per ad- care manage- C: 1.28 (15.51) ditional per- ment. son with clini- d1: .461 cally signifi- Control: d2: 1.148 cant im- Routinely d3 (I1 vs. I2): provement in available non- .692 outcome on specialist psy- GAS): chiatric ser- £2,660 vices. ICER (per additional per- Measures: son with clini- 1-year follow- cally signifi- up cant improvement in outcome on PST): £2,993

Borderline Personality Disorder While the above studies do include persons with Borderline Personality Disorder (BPD), a subset of cost-effectiveness studies focuses exclusively on this disorder.

A long-term study measured the cost-effectiveness of adding a year of Cognitive Behavioral Therapy for personality disorders (CBT-PD) to treatment as usual in the United Kingdom. After six years, 54% of the participants no longer met diagnostic criteria for BPD, and there were no significant differences on any clinical measures or costs. CBT was more clinically effective than usual care at earlier time points including at end of treatment at two years. Moreover, average total costs continued to be lower for CBT (£6,582) compared to treatment as usual (£18,737), suggesting cost-effectiveness with better to similar clinical effectiveness and lower costs (Davidson et al., 2010; Davidson et al., 2006; Palmer et al., 2006).

Another long-term study compared Schema-Focused Therapy and Transference- Focused Therapy in the Netherlands after four years. Both treatments were offered twice weekly for three years. After four years, Schema-Focused Therapy was significantly more clinically effective at decreasing disorder severity, with a higher number of recovered patients (52% vs. 29%). While total costs between the

173 Personality Disorders two therapies were similar, Schema-Focused Therapy dominated per additional recovered patient and cost an additional €90,457 per QALY, which had an 84% likelihood of being more cost-effective at a standard willingness to pay threshold of €20,000 per QALY (van Asselt et al., 2008). However, it was not compared to usual care to assess overall cost-effectiveness.

As before, one study for BPD also looked specifically at persons who had self- harmed in the previous year in the Netherlands. A joint crisis plan, which included a written document created by participants in collaboration with service providers to outline treatment preferences in advance for the management of future crises, had no significant differences on any clinical outcomes or on total costs compared to treatment as usual after six months (Borschmann et al., 2013). Similarly, Dialectical Behavior Therapy had no clinical or cost differences compared to treatment as usual for patients with personality disorders who self- harm (Priebe et al., 2012).

Table 2. Behavioral Interventions for Borderline Personality Disorder (BPD) Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Borschmann 73 adults with Intervention: Percent Oc- PP: et al. (2013) Borderline Treatment as currence of Healthcare Personality usual plus Self-Harming and Social Joint crisis Disorder who joint crisis Behavior: Services plans for per- self-harmed in plan, a written I: 69.4% sons with the previous document C: 55.6% Total Costs: Borderline 12 months in created by I: £5,308 Personality UK. 37 in in- participant in (5,468) Disorder tervention, 36 collaboration Frequency of C: £5,631 in control. with service Self-Harm Ep- (10,293) providers out- isodes: lining treat- I: 20.6 (89.7) ment prefer- C: 20.3 (67.0) ences for (NS) management of future cri- d: .004 ses. Average cost £146/ No significant participant. difference on any measure. Control: Treatment as usual.

Measures: 6 months Davidson et 76 partici- Intervention: Suicide At- PP: al. (2010 & pants with Treatment as tempts: Healthcare 2006) & Palm- Borderline usual plus 1 year and Social

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness er et al. (2006) Personality Cognitive Be- I: .61 (.95) Services Disorder in havioral C: 1.02 (2.14) Cognitive Be- UK. 84% fe- Therapy for (NS) Total Costs: havioral male. At 6- personality I: £6,582 Therapy vs. year follow- disorders 2 years (6,913) usual care for up, 54% no (CBT-PD) for I: .87 (1.47) C: £18,737 Borderline longer met 30 sessions C: 1.73 (311) (43,998) Personality diagnostic cri- over 1 year. (p=.020) (NS) Disorder teria. 43 in intervention, 33 Control: 6 years No statistically in control. Treatment as I: 1.88 (3.19) significant cost usual. C: 3.03 (4.16) differences, but (p=.061) total costs on Measures: average contin- 6 years No statistically ue to be lower. significant differences on any other measures at 6 years. van Asselt et 86 patients Interventions: Proportion of PP: Societal al. (2008) with Border- (1) Schema- Recovered Pa- line Personali- Focused tients: Total Costs:

Schema- ty Disorder Therapy tar- I1: 52% I1: €200037,826 Focused (BPD) across 4 geting 4 dys- I2: 29% (3,411)

Therapy vs. sites in the functional I2: €200046,795 Transference- Netherlands. schema Border- (5,630) Focused Psy- 44 in interven- modes specif- line Personalit ICER (per chotherapy tion #1, 42 in ic to BPD for y Disorder Se QALY; I1 vs. for Borderline intervention 50-minute verity Index I2):

Personality #2. sessions 2x/ (BPDI): €200090,457 Disorder week for 3 I1: 16.94 years. (11.34) ICER (per re- (2) Transfer- I2: 21.98 covered pa- ence-Focused (11.00) tient): Psychothera- (p=.035) I1 vs. I2 py with nego- Dominant tiated treat- d: .451 ment contract Willingness to between pa- pay threshold: tient and If value is therapist to €20K/QALY, resolve primi- 84% probabil- tive internal- ity Schema- ized object re- Focused Ther- lations for 50- apy more minute ses- cost-effective

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness sions 2x/ than Transfer- week for 3 ance-Focused years. Psychothera- py. Regard- Measures: less of value 4 years per recovered patient, >90% probability more cost- effective.

LIMITATIONS AND FUTURE DIRECTIONS The biggest limitations to identifying cost-effective behavioral interventions for personality disorders include the lack of economic data for the United States and absence of cost-effectiveness studies in America as well as the lack of studies on the nine personality disorders other than Borderline Personality Disorder.

In studies of unspecified or multiple personality disorders, the results are difficult to generalize without further understanding of which components of personality disorders are being targeted in the interventions. In one study that did a secondary analysis by type, it revealed that the cost-effectiveness findings were limited to one of the two types of personality disorders assessed. This supports the idea that the wide range of personality disorders may not all benefit from the same types of interventions. Finally, the high level of comorbidity between multiple personality disorders as well as with other neuropsychiatric disorders may play an important role in evaluating the cost-effectiveness of interventions that target symptoms or behaviors that occur across multiple disorders.

The evolving understanding of how to define and measure personality disorders may be a significant factor in this lack of data and the need for new types of research. Given the high number of persons who currently fall into the classification “Personality Disorder Not Otherwise Specified” (PDNOS) and the proposal under consideration to shift to a less categorical diagnostic system and instead identify key traits common across personality disorders, additional research on both treatment efficacy and associated costs will naturally need to follow.

The majority of cost-effectiveness data available for personality disorders does not use a standard measure of improvement (e.g., QALY) nor establish any willingness to pay thresholds, making it difficult to assess overall cost-effectiveness between treatment options, across studies, or across other disorders. Moreover, many of the comparisons are limited between two types of interventions and not assessed relative to usual care or other type of control. Compared to other disorders reviewed in this book, the incremental cost per improvement on most outcome measures were much higher. However, since the measures are for different outcomes, it is difficult to conclude whether or not the difference is meaningful.

176 Personality Disorders

Lastly, available cost-effectiveness studies were divided between treatment type and delivery modality; however, additional studies are needed for both. While studies comparing specialist/generalist inpatient/outpatient treatment options are valuable, further data need to confirm whether the underlying treatment components (e.g., type of psychotherapy) are also cost-effective options. There is a shocking absence of adequate data to make treatment recommendations for most personality disorders, let alone to assess associated costs. Treatments for personality disorders are often time and resource intensive, so optimizing costs without diminishing overall cost-effectiveness is of particular importance. Until then, no conclusions can be drawn about the cost-effectiveness of behavioral interventions for personality disorders in general or any sub-type in particular.

KEY POINTS All key points for personality disorders are based on results from single studies for interventions outside the United States and without standardized willingness to pay thresholds. Findings should be interpreted cautiously.

Unspecified or Multiple Personality Disorders • A stepped program of inpatient treatment followed by outpatient treatment (longer treatment overall) was more cost-effective than a one-stage program of longer inpatient treatment alone, but its cost-effectiveness compared to routinely available psychiatric services will depend on the willingness to pay threshold. • A stepped program of inpatient treatment followed by outpatient psychotherapy was less cost-effective than outpatient psychotherapy alone after three years, although overall cost-effectiveness will depend on comparison to routine services, as well as the willingness to pay threshold. These findings persisted when limited to patients with Avoidant Personality Disorder, but not when limited to patients with Borderline Personality Disorder. • After three months of inpatient treatment, usual aftercare of two booster sessions at three and nine months dominated a more intensive six-month reintegration program with monthly sessions. • For patients with personality disorders who self-harm, Dialectical Behavioral Therapy with weekly therapy, groups skills training and phone-based coaching had no significant clinical or cost differences compared to usual care after a year, but may be cost-effective per incremental improvement in self-harm, depending on the willingness to pay threshold. • In sum, lower intensity programs appear to be more cost-effective than higher intensity ones, although specific psychotherapies were not compared to each other. Outpatient therapy alone appeared more cost-effective than a stepped program of inpatient treatment followed by outpatient therapy, which in turn appeared more cost-effective than inpatient treatment alone, although whether or not any of these are more cost-effective than routinely available psychiatric services will depend on the willingness to pay threshold. Similarly, a two-session aftercare program was more cost-effective than a six-session one.

177 Personality Disorders

Borderline Personality Disorder • Adding Cognitive Behavioral Therapy to usual care had the potential to be more cost-effective than usual care alone. It was more clinically effective after two years and equally clinically effective after six years, while having lower total costs after six years. • Schema-Focused Therapy dominated Transference-Focused Psychotherapy after four years in terms of number of recovered patients. It had a 84% likelihood of being more cost-effective at a standard willingness to pay threshold; however, it was not compared to usual care to determine overall cost- effectiveness. • For patients who self-harm, a joint crisis plan (i.e. a written agreement between patient and provider for treatment preferences for future crises) had no clinical or cost differences compared to usual care after six months. • In sum, Cognitive Behavioral Therapy appeared more cost-effective than usual care and Schema-Focused Therapy was more cost-effective than Trans- ference-Focused Psychotherapy but was not compared to usual care for Bor- derline Personality Disorders. It is also surprising to note the lack of studies comparing Dialectical Behavior Therapy, which is considered the clinical gold standard for Borderline Personality Disorder. More studies are needed to compare different types of psychotherapies to each other; additionally, delivery modalities could also be compared for Borderline Personality Disorder.

Self-Harm • For patients who self-harm, neither psychosocial intervention tested (Dialec- tical Behavioral Therapy and joint crisis plans) demonstrated any clinical or cost differences to usual care. Given self-harm is one of the possible diagnostic criteria for Borderline Personality Disorder, it warrants further research. It is possible that patients with personality disorders and self-harm behaviors have particularly severe versions of these disorders. See Chapter 6 on Delib- erate Self-Harm for more interventions targeting this behavior.

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Davidson K, Norrie J, Tyrer P, Gumley A, Tata P, Murray H, Palmer S. The effectiveness of cognitive behavior therapy for borderline personality disorder: results from the borderline personality disorder study of cognitive therapy (BOSCOT) trial. J Pers Disord. 2006 Oct;20(5):450-65.

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Grant BF, Hasin DS, Stinson FS, Dawson DA, Chou SP, Ruan WJ, Pickering RP. Prevalence, correlates, and disability of personality disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. J Clin Psychiatry. 2004 Jul;65(7):948-58.

Kvarstein EH, Arnevik E, Halsteinli V, Rø FG, Karterud S, Wilberg T. Health service costs and clinical gains of psychotherapy for personality disorders: a randomized controlled trial of day-hospital-based step-down treatment versus outpatient treatment at a specialist practice. BMC Psychiatry. 2013 Nov 22;13:315.

Lenzenweger MF, Lane MC, Loranger AW, Kessler RC. DSM-IV personality disorders in the National Comorbidity Survey Replication. Biol Psychiatry. 2007 Sep 15;62(6):553-64.

McCrone P, Dhanasiri S, Patel A, Knapp M, Lawton-Smith S. Paying the price: the cost of mental health care in England to 2026. London: King's Fund, 2008.

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Olesen J, Gustavsson A, Svensson M, Wittchen HU, Jönsson B; CDBE2010 study group; European Brain Council. The economic cost of brain disorders in Europe. Eur J Neurol. 2012 Jan;19(1):155-62.

Palmer S, Davidson K, Tyrer P, Gumley A, Tata P, Norrie J, Murray H, Seive- wright H. The cost-effectiveness of cognitive behavior therapy for borderline personality disorder: results from the BOSCOT trial. J Pers Disord. 2006 Oct;20(5):466-81.

179 Personality Disorders

Priebe S, Bhatti N, Barnicot K, Bremner S, Gaglia A, Katsakou C, Molosankwe I, McCrone P, Zinkler M. Effectiveness and cost-effectiveness of dialectical behaviour therapy for self-harming patients with personality disorder: a pragmatic randomised controlled trial. Psychother Psychosom. 2012;81(6):356-65.

Soeteman DI, Hakkaart-van Roijen L, Verheul R, Busschbach JJ. The economic burden of personality disorders in mental health care. J Clin Psychiatry. 2008 Feb;69(2):259-65.

Thunnissen M, Duivenvoorden H, Busschbach J, Hakkaart-van Roijen L, van Til- burg W, Verheul R, Trijsburg W. A randomized clinical trial on the effectiveness of a reintegration training program versus booster sessions after short-term inpatient psychotherapy. J Pers Disord. 2008 Oct;22(5):483-95.

Tyrer P, Mulder R, Crawford M, Newton-Howes G, Simonsen E, Ndetei D, Kol- dobsky N, Fossati A, Mbatia J, Barrett B. Personality disorder: a new global perspective. World Psychiatry. 2010 Feb;9(1):56-60. van Asselt AD, Dirksen CD, Arntz A, Giesen-Bloo JH, van Dyck R, Spinhoven P, van Tilburg W, Kremers IP, Nadort M, Severens JL. Out-patient psychotherapy for borderline personality disorder: cost-effectiveness of schema-focused therapy v. transference-focused psychotherapy. Br J Psychiatry. 2008 Jun;192(6):450-7.

Verheul R, Widiger TA. A meta-analysis of the prevalence and usage of the personality disorder not otherwise specified (PDNOS) diagnosis. J Pers Disord. 2004 Aug;18(4):309-19.

180 Self-Harm

CHAPTER 6: DELIBERATE SELF-HARM

ABSTRACT Deliberate self-harm is intentional physical harm to oneself—a maladaptive coping strategy in response to negative emotions or situations. This includes both non-suicidal self-harm (e.g., cutting, burning, hitting), suicidal self-harm (e.g., gunshots, hanging, overdose), and self-harm where intent is unclear. Self-harm commonly co-occurs with other neuropsychiatric disorders, occurs most frequently in adolescents, and results in death more frequently when lethal means are readily available (e.g., gun in home).

U.S. prevalence is broadly estimated at 7.5% to 8% for children, 10% to 23% for adolescents, and 1% to 5.9% for adults. The economic burden was estimated at $32 billion in 2000, of which almost all of it ($31 billion) was due to lost productivity. Unfortunately, there is little evidence for clinically effective treatments, which in turn leads to sparse cost-effectiveness data. In the cost-effectiveness trials reviewed, none demonstrated clinical efficacy. Furthermore, no trials available to date were in the U.S. population. For young people who engaged in prior self-harm, neither a brief Home-Based Family Intervention nor Developmental Group Therapy were cost-effective compared to usual care. However, both adult interventions required limited in-person support, decreasing costs and increasing cost-effectiveness. For adults who engaged in prior self-harm, manual-based brief Cognitive Behavioral Therapy had greater than 90% likelihood of being more cost-effective than usual care for reducing self-harm, and 44% to 88% likelihood of being more cost-effective for improving quality of life. For adults with mild to moderate suicidal thoughts, an unguided web-based self-help intervention based on cognitive behavioral techniques was cost-saving relative to a waiting list control at $41,325 saved per person who significantly decreased suicidal ideation after six weeks, although studies of longer duration are warranted.

In addition, public health interventions outside of healthcare settings have focused on reducing suicide. Three main approaches include providing support services (e.g., crisis hotlines), reducing access to lethal means (e.g., regulating guns or medications), and increasing barriers (e.g., at bridges and train platforms). The current data suggest the costs of implementing these interventions are justified by the value of the lives saved by them. More effective clinical interventions must be developed prior to any meaningful assessments of cost- effectiveness. In the meantime, additional economic evaluations of public health interventions may reveal other cost-effective solutions.

BACKGROUND ON DISORDER Individuals who engage in self-harming behaviors may or may not have suicidal intent. However, even when self-harming behaviors are not intended to end one’s life, they can still become life threatening. Self-harm is also an important risk factor for suicide: people who self-harm are more likely to later attempt suicide.

Broadly, self-harm is intentional and deliberate physical harm to one’s own body. The most common self-harm behavior is cutting with sharp or jagged ob-

181 Self-Harm jects. However, self harming also includes behaviors like burning, poisoning, hitting, or pulling out hair, as well as putting oneself in dangerous situations or neglecting oneself. Self-harm is believed to be a maladaptive coping strategy in response to negative emotions like pain, anger, frustration, or anxiety. Self-harm may provide some distraction or relief in the short-term, but is often followed by the return of the original negative emotions as well as guilt and shame for the self-harming behaviors.

Suicide specifically refers to self-harm with the intent to end one’s life, often in reaction to stressful or overwhelming life experiences that lead to feelings of hopelessness (e.g., end of a relationship, diagnosis of terminal illness). Suicide attempts may be efforts to decrease feelings of rejection, loss, or loneliness; of shame, guilt, or burden; or of being a victim. Suicidal behaviors are usually limited to gunshots, poisoning, overdose, hanging, and jumping from a height. Im- portantly, many suicide attempts, especially overdose, are not successful; the attempt might not be fatal or rescue might be possible. In such cases, these attempts may be intended as a signal that the person needs help. Given this, the spectrum of self-harm with or without suicidal intent is difficult to disentangle and we will use the term self-harm to refer to the full spectrum of behaviors.

Self-harm is rooted in a complex combination of biological, psychological, social, and cultural factors, as well as negative life experiences (Hawton et al., 2012). Both self-harming behaviors and suicidal thoughts often co-occur with other neuropsychiatric disorders, although the specific disorders differ depending on whether it is self-harm with or without suicidal intent. This co-occurrence is estimated within a broad range from 40% to 87% for adolescents and 2% to 20% in adults (Hawton et al., 2012; Kerr et al., 2010). Thus, interventions for self-harm are often part of broader treatment plans. The full extent of co-occurrences will not be reviewed here; however, it is worth noting that Borderline Personality Disorder is the only disorder where self-harm can be a diagnostic criterion (see Chapter 5) and that Depressive Disorders have a clear relationship with suicide (see Chapter 2). Notably, self-harm and suicide also occur more commonly in certain populations, such as homosexual, bisexual, or transgender persons (e.g., King et al., 2008).

Availability of lethal means, particularly guns, has been shown to be a risk factor for suicide. While gun owners do not have more or less mental health problems and are not more or less likely to commit suicide, those who are feeling suicidal and have access to a gun are more likely to complete suicide. This is especially true for young people, for whom more than half of all suicides are completed by gun. If an adolescent uses a gun to commit suicide, the gun typically belongs to a parent or other family member (Harvard, 2015).

PREVALENCE OF DISORDER Self-harm is of particular concern for youth. Self-harm rates are high during adolescence and suicide is the second leading cause of death for young people globally (Hawton et al., 2012). Crucially, there appears to be an increasing trend for self-harm in adolescents and young adults (Kerr et al., 2010). For children under age 12, limited data exist but prevalence for non-suicidal self-harm is estimated

182 Self-Harm at 7.5% to 8%. Self-harm often starts in adolescence, with the highest rate of self- harm between the ages of 15 and 24 years. For adolescents, prevalence is estimated at 10% to 23%, with more than half reporting self-harming more than once (Hawton et al., 2012; Washburn et al., 2012; Kerr et al., 2010; Corso et al., 2007). For adults, non-suicidal self-harm is estimated at 1% to 5.9% (Kerr et al., 2010; Klonsky, 2011). While most suicide rates have been decreasing or only increasing marginally, the suicide rate for persons age 35 to 64 years increased by 28.4% from 1999 to 2010. It has been suggested that part of the cause was the economic recession. In both adolescents and adults, self-harm occurs more frequently in females than males. However, while women are more likely to attempt suicide, men are more likely to complete suicide. Self-harm now surpasses the number of lives lost to car accidents and is ranked sixth for years of life lost, following ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury (CDC, 2013; US Burden of Disease Collaborators, 2013).

ECONOMIC BURDEN OF DISORDER In 2000, the total lifetime direct and indirect costs of self-harm in the United States were estimated at $33 billion, of which $32 billion was due to lost productivity and only $1 billion to healthcare. Further, 91% of these costs ($30.4 billion) were estimated to be due to the 9% of self-harm cases ending in suicide (Corso et al., 2007). The costs of self-harm include direct costs like emergency room attendance and hospitalization as well as indirect costs like productivity losses due to illness and premature death. As counterpoint, some researchers suggest that any economic assessment of suicide should consider the potential savings to society, such as funds not spent for treating underlying psychiatric disorders or caring for persons into old age (Yang & Lester, 2007).

CLINICALLY EFFECTIVE INTERVENTIONS There is currently little evidence for effective pharmacotherapeutic or psychotherapeutic options to prevent or decrease deliberate self-harm (Hawton et al., 2012; Washburn et al., 2012). In fact, although treatment increased significantly from 1990 to 2000, there was not a corresponding decrease in suicidal thoughts or behaviors (Kessler et al., 2005). Given this, treatment guidelines for deliberate self-harm in the United States typically utilize interventions effective for co- occurring conditions or specific symptoms and not specifically for self-harm.

No medications are specifically approved for self-harm or suicidal thoughts and behaviors; however, a few preliminary studies show promise (Kerr et al., 2010). Notably, pharmacotherapy for associated neuropsychiatric diagnoses (e.g., antidepressants for Depressive Disorders, lithium for Bipolar Disorders, clozapine for Schizophrenic Disorders) may also alleviate self-harm by targeting specific symptoms and improving overall mental health. Medication may also be recommended for related symptoms such as insomnia, agitation, anxiety, or panic attacks. In certain cases (e.g., catatonia, pregnancy), electroconvulsive therapy (ECT) may be recommended for short-term benefits, though typically in combination with other treatments with longer-term benefits.

No psychotherapy studies have focused exclusively on non-suicidal self-harm (Kerr et al., 2010). In general, psychotherapy is commonly recommended for self-

183 Self-Harm harm, including but not limited to Cognitive Behavioral Therapy, Dialectical Be- havior Therapy, Psychodynamic Psychotherapy, Problem-Solving Therapy, Mindfulness-Based Therapy, and Family or Couples Therapy. As with pharmacotherapy, these are largely based on recommendations for common co- occurring disorders. Large-scale evaluations of clinical and cost-effectiveness for deliberate self-harm are still needed for most of these psychotherapeutic options.

The psychotherapies for which cost-effectiveness data are available include Cog- nitive Behavioral Therapy (CBT), which is characterized by identifying and targeting maladaptive thoughts and behaviors that may contribute to self-harm. CBT may be particularly effective in decreasing feelings of hopelessness and suicide attempts in depressed persons. Additionally, manual-assisted CBT is designed to be a brief therapy that integrates Problem-Solving Therapy with cognitive techniques and relapse prevention strategies. Problem-Solving Therapy provides training in problem-solving and goal-setting skills to tackle psychosocial challenges and interpersonal issues. Family Therapy is characterized by working with family members of the self-harming person, including on interpersonal communication, behavioral techniques, and problem-solving skills. Developmen- tal Group Psychotherapy is designed for adolescents and integrates Psychody- namic Therapy, Dialectical Behavioral Therapy (DBT), and problem-solving skills. Psychodynamic Therapy is designed to increase self-awareness, especially around how one’s past influences one’s present behaviors, and DBT focuses on the acceptance of thoughts, feelings and behaviors, even if they are uncomfortable or undesired, while acknowledging the need for change. Both Psychodynam- ic Therapy and DBT are also recommended for Borderline Personality Disorder, in which self-harm is a diagnostic criterion.

COST-EFFECTIVENESS OF CLINICAL INTERVENTIONS Limited cost-effective data are available for clinical interventions for self-harm, with no trials taking place in the United States.

Self-Harm in Children and Adolescents For children and adolescents (less than 16 years old) who deliberately poisoned themselves in the United Kingdom, the addition of a brief Home-Based Family Intervention had no advantages over usual care alone after six months. The Home-Based Family Intervention consisted of four home-based visits from a psychiatric social worker focused on intrafamilial communication, behavioral techniques and problem-solving There were no significant differences on any clinical outcome or in total costs, although parental satisfaction was higher for the intervention after two months. In an analysis limited to non-depressed children, suicidal ideation was significantly lower in the intervention than routine care, suggesting the potential for the intervention to be cost-effective for this subpopulation (Byford et al., 1999; Harrington et al., 1998).

For adolescents (12 to 17 years old) with at least two prior episodes of self-harm in the preceding year in the United Kingdom, the addition of a manual-based Developmental Group Therapy program also had no advantages over usual care alone after a year. There were no significant differences on any clinical outcomes including number of episodes of self-harm or in total costs, indicating the Devel-

184 Self-Harm opment Group Therapy would not be cost-effective at any willingness to pay threshold (Green et al., 2011).

Table 1. Behavioral Interventions for Self-Harm in Children and Adolescents Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Green et al. 304 adoles- Intervention: Health of the PP: Societal (2011) cents (age 12- Routine care Nation Out- 17 years) with plus manual- come Scales Total Costs:

Developmen- at least two based Devel- for Children I: £200621,781 tal Group past episodes opmental and Adoles- (38,794)

Therapy for of self- Group Thera- cents: C: £200615,372 adolescents harm within py program I: 10.9 (5.9) (24,981) with repeated previous 12 designed for C: 11.7 (6.7) (NS) self-harm months in UK. adolescents (NS) (Assessment 151 in inter- who self-harm Willingness to of Treatment vention, 153 with 6 weekly d: .127 pay threshold: In Suicidal in control. sessions and Developmen- Teenagers booster phase Mood and tal Group ASSIST Trial) of weekly Feelings Therapy is not groups as Question- more cost- long as need- naire: effective than ed. I: 24.4 (16.6) routine care at C: 24.6 (17.6) any value. Control: (NS) Routine care. d: .012 Measures: 1 year Suicidal Idea- tion Ques- tionnaire: I: 48.3 (42.7) C: 49.2 (46.8) (NS)

d: .020 Byford et al. 149 children Intervention: Mean Differ- PP: Societal (1999) & Har- (age ≤16 Routine care ence in Sui- rington et al. years) with plus brief cidal Ideation Total Costs (1998) diagnosis of Home-Based Question- (per child):

deliberate Family inter- naire: I: £19981,751.45 Home-Based self-poisoning vention, in- -5.1 (95% CI, (95% CI, Family Inter- (i.e. intention- cluding as- -17.5 to 7.3) 1,169.09 to vention for al overdose) sessment ses- 2,333.82) children and in UK. 90% sion and 4 Mean Differ- C: £19981,455.18 adolescents female. 74 in home-based ence in Hope- (95% CI, who deliber- intervention, visits by psy- lessness Scale: 1,087.62 to

185 Self-Harm

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness ately poi- 75 in control. chiatric social .2 (95% CI, 1,822.74) soned them- workers with -.9 to 1.3) (NS) selves with intensive, family- centered ses- No significant sions on intra- differences on familial com- any clinical munication, outcomes. For behavioral subset of non- techniques, depressed pa- and problem- tients, signifi- solving. cantly less suicidal ideation in Control: intervention Routine care. than routine care. Measures: 6 months

Self-Harm in Adults For adults with a prior history of self-harm in the United Kingdom, a manual- based brief Cognitive Behavioral Therapy intervention had a greater than 90% likelihood of being more cost-effective than usual care at decreasing self-harm after a year, at £120 saved per 1% reduction in the number of persons who self- harm. Notably, although it cost £66,000 per QALY, the intervention still had a 44% to 88% likelihood of being more cost-effective than usual care by this metric, despite being marginally less effective. This shows that despite the lack of significant differences in any clinical outcomes or in total costs per person after 12 months, manual-based Cognitive Behavioral Therapy would still be the more cost-effective option (Byford et al., 2003; Tyrer et al., 2003).

One trial looked at self-harm thoughts rather than behaviors. For adults with mild to moderate suicidal thoughts in the Netherlands, an unguided web-based self-help intervention with six weekly modules was cost-saving at $41,325 per person who responded to the treatment (i.e. decreased their score on a measure of suicidal thoughts) compared to waiting list control after six weeks. Even if no value were assigned to improving this outcome, the self-help intervention had a greater than 90% likelihood of being more cost-effective than the waitlist (van Spijker et al., 2012). While these results align with similar cost-effectiveness findings for guided and unguided web-based self-help interventions for Depressive Disorders, which often include suicidal thoughts, assessments over longer duration are needed to confirm whether cost-savings persist after treatment is over.

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Table 2. Behavioral Interventions for Self-Harm in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness van Spijker et 236 adults Intervention: Percent PP: Societal al. (2012) with mild to Usual care Treatment Re- moderate sui- plus unguid- sponse (≥6.48 ICER (per ad- Unguided cidal thoughts ed web-based improvement ditional web-based in the Nether- self-help with on Beck Scale treatment re- self-help to lands. 66.1% 6 weekly for Suicidal sponse): reduce suicid- female. 116 in modules Ideation): -$200941,325 al ideation intervention, based on cog- I: 35.3% 120 in control. nitive behav- C: 20.8% Willingness to ioral tech- (p=.01) pay threshold: niques to re- If no value per duce frequen- treatment re- cy and inten- sponder, 93% sity of suicidal probability ideation. Es- unguided timated costs web-based

$2009176/partic self-help more ipant. 22.4% cost-effective did not start than waiting intervention. list. If value is 21.6% com- €30K/treatme pleted whole nt responder, intervention. 98.5% probability more Control: cost-effective. Usual care plus waitlist with link to information- only website.

Measures: 6-week follow-up Byford et al. 397 patients Intervention: Percent with PP: Societal (2003) & Tyrer (age 16-65 Manual- Repeated Epi- et al. (2003) years) with assisted brief sode of Delib- ICER (per history of re- Cognitive Be- erate Self- QALY):

Brief Cogni- current delib- havioral harm: £200066,000 tive Behavior- erate self- Therapy. Pa- I: 39% al Therapy for harm in UK. tients sent C: 46% ICER (per 1%- recurrent de- 197 in inter- treatment (NS) change in liberate self- vention, 200 manual and proportion of harm in control. offered up to persons with (POPMACT 7 sessions No significant repeat self-

187 Self-Harm

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Study) with trained differences on harm epi- therapist. any secondary sode):

measure (e.g., -£2000120 Control: anxiety, depres- Treatment as sion, social Willingness to usual. functioning). pay threshold: If value is £0 Measures: to £66K/ 12 months QALY, brief Cognitive Be- havioral Therapy more likely cost- effective than usual care. If value >£6K, usual care more likely cost-effective. For 1% change in proportion of persons with repeat self-harm episode, >90% probability more cost- effective at all values.

MODELED COSTS OF PUBLIC HEALTH APPROACHES Public health, rather than clinical, interventions have been a large focus of suicide prevention efforts. Common public health interventions focus on three main approaches: (1) providing support services for persons in crisis or with suicidal intent, (2) reducing access to lethal means, which might increase the likelihood that a suicide attempt might be survived or (3) increasing barriers to suicide, such that attempts require more time and effort, and are therefore less likely to be carried out impulsively. Almost all of these public health interventions are either infeasible or unethical to test in randomized clinical trials, and thus gold- standard trials will likely never be conducted to establish their cost-effectiveness. However, models have been developed to provide some estimates of cost- effectiveness of these public health approaches. Given the paucity of literature on clinical aspects and cost-effectiveness of suicide interventions, and recent interest in incorporating some elements of these public health interventions into healthcare delivery models, we present estimates from some of these models here. As before, the majority of data are from outside of the United States.

188 Self-Harm

Support Services Crisis hotlines are the most common example of the support services approach. In general, crisis lines (i.e. hotlines, helplines, warmlines) are considered low-cost options compared to traditional in-person health services.

One model from Belgium assessed a telephone and chat helpline for suicide prevention and estimated it to be cost-saving over ten years. The helpline cost €218,899 to run but saved €1,452,022 in healthcare costs. It also had a modest impact on QALYs for most participants except for women using chat services, for whom there was no effect on QALYs (Pil et al., 2013).

A unique model from Australia focused on a post-intervention (StandBy Re- sponse Service) for those bereaving the loss of a loved one to suicide, with the intent to decrease distress and reduce future suicides. The intervention included a national 24-hour crisis line as a centralized contact as well as face-to-face support and referral services as needed. StandBy Response Service was cost-saving at Australian $803 less than no intervention in total costs. StandBy Response Service would be considered dominant since it also increased QALYs (Comans et al., 2013).

Reducing Access to Lethal Means As described earlier, access to lethal means increases risk for suicide. Thus, making access more difficult can reduce risk of suicide. Interventions to restrict access to lethal means include efforts focused on gun safety and on preventing poisoning. Gun focused interventions include regulations to reduce access to guns or ammunition, gun lock programs, gun safe removal and temporary storage programs. Poisoning prevention efforts include medication take-back programs, or restrictions on volume of dispensing of medication. Some even recommend classifying certain painkillers (e.g., acetaminophen) as prescription-only. Inter- ventions to increase access to rescue services might also be considered in this category. For example, opioid overdose education and naloxone distribution programs provide at-risk patients or their significant others education on recognition of opioid overdose and a rescue medication, naloxone, to reverse an intentional or accidental opioid overdose.

Increasing Barriers Interventions to increase barriers to suicide can sometimes overlap with those restricting access to lethal means, but can also include approaches such as pack- aging medications commonly used for suicide attempts in blister packs so that opening a lethal dose takes time, and adding fencing or other barriers around bridges and train tracks.

A model estimated the cost per life saved based on development of a suicide barrier on the Golden Gate Bridge at $180,419 (Whitmer & Woods, 2013). The model assumed that suicide attempts would continue at the rate observed between 1936 and 2006, would have the previously observed fatality rate (98%), and that all attempts prevented by the barrier would be carried out by jumping off another structure (average fatality rate of 47%). Costs were estimated at $50 million for development of the barrier and $78,000 per year in maintenance. This estimate is

189 Self-Harm far below the Department of Transportation’s standard estimate of the value of a life saved (averaging $6 million, with a range of $3.2-8.4 million; USDOT, 2009).

A model from Japan assessed the effect of installing blue lights on train platforms to prevent suicides by railway or metro, and concluded there was an 84% decrease in the number of suicides over ten years. As installing lights is easier and less expensive than physical barriers such as screen doors, this suggests this could be a cost-effective option compared to other barrier options for suicide prevention at train platforms (Matsubayashi et al., 2013).

LIMITATIONS AND FUTURE DIRECTIONS In addition to the need for additional cost-effectiveness trials, the biggest limitation is the lack of clinically effective treatments. The lack of significant clinical improvements on any measure not only decreases the likelihood of cost- effectiveness but also confirms that the needs of self-harming patients are not being adequately met.

Clearly, the high occurrence of self-harm in adolescence has significant economic implications. It is particularly important to investigate treatment for young people in order to maximize the long-term cost benefits. In this review, neither of the interventions targeting young people demonstrated cost-effectiveness. Of note, one of the adult interventions showed that thinking about self-harm – even without engaging in self-harm behaviors – contributes to overall societal costs. While it is more difficult to assess thoughts than behaviors, it signals the importance in understanding the underlying mental states linked with deliberate self-harm. Early screening or intervention programs may offer another avenue of research.

Given the extensive co-occurrence with other neuropsychiatric disorders, there is a possibility of immense heterogeneity for effective treatments; different interventions may be more or less effective depending on other conditions. Self-harm can also occur outside any co-occurring conditions, for which treatment options may differ as well. In short, developing a better understanding of the underlying mechanisms and epidemiology and then developing corresponding treatments for the different sub-populations will enable assessments for cost-effectiveness.

Lastly, despite the logistical and ethical barriers to conducting gold standard randomized cost-effectiveness trials for public health interventions, these data provide insights into alternative solutions in cases where clinically effective solutions are current unavailable. To prevent self-harm, they warrant further investigation.

KEY POINTS • There is currently not enough data to draw meaningful conclusions about cost-effective behavioral interventions to reduce self-harm. No studies occurred in the United States, and all studies lacked clinical efficacy. Public health models may provide alternatives.

190 Self-Harm

Clinical Interventions • In children with prior self-harm, a brief Home-Based Family Intervention was not cost-effective relative to usual care with no differences in clinical outcomes or total costs after six months; however, there was a significant reduction in suicidal ideation for non-depressed children, which suggests it could be more cost-effective for this sub-population.

• In adolescents with prior self-harm, manual-based Developmental Group Therapy was not cost-effective relative to usual care at any willingness to pay threshold after one year.

• In adults with prior self-harm, manual-assisted brief Cognitive Behavioral Therapy had more than 90% likelihood of being more cost-effective than usual care for reducing self-harm after one year, and a 44% to 88% likelihood of being more cost-effective for improving quality of life.

• In adults with mild to moderate suicidal thoughts, an unguided web-based self-help intervention based in cognitive behavioral techniques had a more than 90% probability of being cost-saving over usual care. Studies over longer durations are warranted.

Public Health Interventions • Public health interventions for suicide prevention cannot truly test cost- effectiveness but data support cost-offset in terms of lives saved. Three main approaches are: (1) providing support services, (2) reducing access to lethal means, and (3) increasing barriers to suicide.

• Low-cost supportive services include crisis telephone lines. Both a suicide prevention helpline and a post-suicide national crisis line (for those bereaving the loss of a loved one to suicide) were considered cost-effective with lower costs of implementation compared to the estimated costs of lives saved.

• Access to lethal means is known to increase suicide risk. Reducing access to lethal means includes regulations around gun and ammunition access, storage, and removal as well as regulations around medication dispensation and return. It is postulated that the costs of implementing these reductions would be outweighed by the costs of lives saved.

• Barriers can increase the time and effort required for suicide attempts, decreasing the likelihood they will be carried out impulsively. Barriers at two popular suicide sites were considered cost-effective: Building a physical barrier at a bridge was estimated to cost substantially less per death prevented than the standard value of a life saved, and using blue lights at train platforms was easier and less expensive than building a physical barrier while still being effective at decreasing suicides.

191 Self-Harm

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Byford S, Knapp M, Greenshields J, Ukoumunne OC, Jones V, Thompson S, Tyrer P, Schmidt U, Davidson K; POMACT Group. Cost-effectiveness of brief cognitive behaviour therapy versus treatment as usual in recurrent deliberate self-harm: a decision-making approach. Psychol Med. 2003 Aug;33(6):977-86. Centers for Disease Control and Prevention (CDC). Suicide among adults aged 35-64 years--United States, 1999-2010. MMWR Morb Mortal Wkly Rep. 2013 May 3;62(17):321-5.

Comans T, Visser V, Scuffham P. Cost effectiveness of a community-based crisis intervention program for people bereaved by suicide. Crisis. 2013 Jan 1;34(6):390- 7.

Corso PS, Mercy JA, Simon TR, Finkelstein EA, Miller TR. Medical costs and productivity losses due to interpersonal and self-directed violence in the United States. Am J Prev Med. 2007 Jun;32(6):474-482.

Green JM, Wood AJ, Kerfoot MJ, Trainor G, Roberts C, Rothwell J, Woodham A, Ayodeji E, Barrett B, Byford S, Harrington R. Group therapy for adolescents with repeated self harm: randomised controlled trial with economic evaluation. BMJ. 2011 Apr 1;342:d682.

Harrington R, Kerfoot M, Dyer E, McNiven F, Gill J, Harrington V, Woodham A, Byford S. Randomized trial of a home-based family intervention for children who have deliberately poisoned themselves. J Am Acad Child Adolesc Psychia- try. 1998 May;37(5):512-8.

Harvard Injury Control Research Center. Firearms Research: Suicide. Retrieved March 17, 2015, from http://www.hsph.harvard.edu/hicrc/firearms- research/gun-ownership-and-use/

Hawton K, Saunders KE, O'Connor RC. Self-harm and suicide in adolescents. Lancet. 2012 Jun 23;379(9834):2373-82.

Kerr PL, Muehlenkamp JJ, Turner JM. Nonsuicidal self-injury: a review of current research for family medicine and primary care physicians. J Am Board Fam Med. 2010 Mar-Apr;23(2):240-59.

Kessler RC, Berglund P, Borges G, Nock M, Wang PS. Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990-1992 to 2001-2003. JAMA. 2005 May 25;293(20):2487-95.

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King M, Semlyen J, Tai SS, Killaspy H, Osborn D, Popelyuk D, Nazareth I. A systematic review of mental disorder, suicide, and deliberate self harm in lesbian, gay and bisexual people. BMC Psychiatry. 2008 Aug 18;8:70.

Klonsky ED. Non-suicidal self-injury in United States adults: prevalence, socio- demographics, topography and functions. Psychol Med. 2011 Sep;41(9):1981-6.

Matsubayashi T, Sawada Y, Ueda M. Does the installation of blue lights on train platforms prevent suicide? A before-and-after observational study from Japan. J Affect Disord. 2013 May;147(1-3):385-8.

Pil L, Pauwels K, Muijzers E, Portzky G, Annemans L. Cost-effectiveness of a helpline for suicide prevention. J Telemed Telecare. 2013 Jul;19(5):273-81.

Tyrer P, Thompson S, Schmidt U, Jones V, Knapp M, Davidson K, Catalan J, Air- lie J, Baxter S, Byford S, Byrne G, Cameron S, Caplan R, Cooper S, Ferguson B, Freeman C, Frost S, Godley J, Greenshields J, Henderson J, Holden N, Keech P, Kim L, Logan K, Manley C, MacLeod A, Murphy R, Patience L, Ramsay L, De Munroz S, Scott J, Seivewright H, Sivakumar K, Tata P, Thornton S, Ukoumunne OC, Wessely S. Randomized controlled trial of brief cognitive behaviour therapy versus treatment as usual in recurrent deliberate self-harm: the POPMACT study. Psychol Med. 2003 Aug;33(6):969-76.

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US Burden of Disease Collaborators. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA. 2013 Aug 14;310(6):591-608. van Spijker BA, Majo MC, Smit F, van Straten A, Kerkhof AJ. Reducing suicidal ideation: cost-effectiveness analysis of a randomized controlled trial of unguided web-based self-help. J Med Internet Res. 2012 Oct 26;14(5):e141.

Washburn JJ, Richardt SL, Styer DM, Gebhardt M, Juzwin KR, Yourek A, Al- dridge D. Psychotherapeutic approaches to non-suicidal self-injury in adolescents. Child Adolesc Psychiatry Ment Health. 2012 Mar 30;6(1):14.

Whitmer DA, Woods DL. Analysis of the cost effectiveness of a suicide barrier on the Golden Gate Bridge. Crisis. 2013;34(2):98-106.

Yang B, Lester D. Recalculating the economic cost of suicide. Death Stud. 2007 Apr;31(4):351-61.

193 Eating Disorders

CHAPTER 7: EATING DISORDERS

ABSTRACT Eating disorders, which include Anorexia Nervosa, Bulimia Nervosa, Binge Eat- ing Disorder, and Eating Disorders Not Otherwise Specified, comprise patterns of abnormal eating behaviors. These disorders occur more frequently in women. Onset often occurs in adolescence, with 2.7% of adolescents meeting criteria for an eating disorder in their lifetime. In adults, 0.6% will experience Anorexia, 1.0% will experience Bulimia, and 2.8% will experience Binge Eating Disorder.

Data on the economic burden of eating disorders in the United States is limited. In Australia, the direct healthcare costs of eating disorders were estimated at Au$22 million annually. In Germany, the direct and indirect costs of eating disorders were estimated at €319 million annually. Like most disorders, these cost estimates are likely to be underestimates that do not include all the indirect negative consequences of these disorders. Currently, limited cost-effectiveness analyses exist for eating disorders. In adolescents, we identified two studies: specialist outpatient treatment may be more cost-effective than standard inpatient or outpatient treatment for Anorexia, and Family Therapy and guided Cognitive Behavioral Therapy (CBT)-based self-care were similarly cost-effective for Bulim- ia and Eating Disorders Not Otherwise Specified.

No studies were available for Binge Eating Disorder in adolescents. In adults, no studies were available for Anorexia. For Bulimia, three studies in women concluded that medication, telehealth CBT and stepped care CBT may be relatively more cost-effective than traditional in-person CBT. For recurrent Binge Eating Disorder, the only study available found adding CBT-guided self-help to treatment as usual was cost-saving. Overall, more data are needed before conclusions can be drawn about the cost-effectiveness of behavioral interventions for Anorex- ia, Bulimia, Binge Eating Disorder, and Eating Disorders Not Otherwise Speci- fied in both adolescents and adults.

BACKGROUND ON DISORDER Eating disorders involve abnormal eating behaviors that can lead to severe health consequences. There are only a few major types of eating disorders:

• Anorexia Nervosa is characterized by distorted body image and fear of weight gain. Persons with Anorexia will believe they are overweight even when they are extremely underweight, and engage in self-starvation and/or excessive exercise leading to severe weight loss. Persons with Anorexia often struggle with perfectionism and may respond to stress with attempts to regulate weight.

• Bulimia Nervosa is also characterized by body image and weight concerns. Persons with Bulimia are of average- or overweight, and experience repeated episodes of binge eating followed by attempts to compensate for the overeat- ing, commonly with behaviors such as induced vomiting, laxative use, fasting, or excessive exercise.

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• Binge Eating Disorder is also characterized by repeated episodes of binge eating, but without the extreme behaviors to attempt to compensate for overeat- ing that are seen in Bulimia Nervosa.

• Eating Disorders Not Otherwise Specified (EDNOS) is a classification used for eating disorders that do not meet diagnosis criteria for Anorexia and Bu- limia. Binge Eating Disorder is sometimes included in this category.

PREVALENCE OF DISORDER Initial onset of eating disorders commonly occurs in adolescence, with adult age of onset most often between 18 to 21 years. Among U.S. adolescents (age 13 to 18 years), lifetime prevalence for any eating disorder was 2.7%, or 0.3% for Anorex- ia, 0.9% for Bulimia, and 1.6% for Binge Eating Disorder (Swanson et al., 2011). Among U.S. adults, lifetime prevalence was 0.6% for Anorexia, 1.0% for Bulimia, and 2.8% for Binge Eating Disorder (Hudon et al., 2007). Notably, data indicate that Eating Disorders Not Otherwise Specified (which can include Binge Eating Disorder and related symptoms) occurs more frequently than both Anorexia and Bulimia combined and can have comparable economic and health consequences.

Eating disorders are significantly more common in women. Additionally, more than half of people with eating disorders also meet criteria for at least one additional neuropsychiatric disorder (56.2% with Anorexia Nervosa, 94.5% with Bu- limia Nervosa, 78.9% with Binge Eating Disorder; Hudson et al., 2007). Eating disorders also influence physical health since they can disrupt neuroendocrine function and/or lead to nutritional deficiencies (Patrick, 2002). Anorexia Nervosa has the highest mortality rate of any neuropsychiatric disorder (Agras, 2001; Si- mon et al., 2005), and Bulimia Nervosa and Eating Disorders Not Otherwise Specified also have elevated mortality rates (Crow et al., 2009a). Risk of death has been found to be three times higher for eating disorders than for depression, schizophrenia or alcoholism (Simon et al., 2005).

ECONOMIC BURDEN OF DISORDER There is limited research available on the economic burden of eating disorders, although there is clear evidence they exert a significant toll. The best data currently available are from comparable developed nations, although they do not provide a consistent picture nor always include broader estimates of societal costs beyond those incurred by healthcare systems. Even the healthcare estimates are likely to be underestimates given eating disorders are under-diagnosed and under-treated. Moreover, estimates are often limited to Anorexia and Bulimia despite data for the higher prevalence of Eating Disorders Not Otherwise Speci- fied, including Binge Eating Disorder, which have comparable economic and health consequences.

In the United States, no population-wide estimates were available. In terms of treatment costs, 1.1% of annual mental health claims in a national insurance database were for an eating disorder in 1995. For women, the average cost of treat-

195 Eating Disorders ment was estimated at $6,045 for Anorexia, $2,962 for Bulimia, and $3,207 for Eating Disorders Not Otherwise Specified (Striegel-Moore et al., 2000; Agras, 2001). A global review (with two-third of studies from the United States) standardized costs across countries by correcting for the relative value of each currency (i.e. purchasing power parity) and found that annual treatment costs per eating disorder patient were between $1,288-$8,042 (Stuhldreher et al., 2012), similar to the earlier estimates. Ultimately, these treatment costs, along with population prevalence rates, could be used to estimate part of the economic burden in the United States, but do not capture costs related to those who are undiagnosed or untreated nor the broader societal costs of these disorders.

In Australia, annual public and private healthcare expenditures for eating disorders were estimated to be Au$22 million as of 1993/1994. In the United King- dom, healthcare costs of Anorexia Nervosa alone were estimated to be only £4.2 million annually as of 1990; however, it was hypothesized these lower costs may be due to a relatively higher threshold for in-patient admissions and related under-provision of services (Simon et al., 2005). In Germany, annual healthcare insurance costs were estimated to be €65 million for Anorexia Nervosa and €10 million for Bulimia Nervosa as of 1998. Adding indirect costs (e.g., lost productivity, premature death) brought the estimates up to €195 million (67% indirect costs) for Anorexia Nervosa and €124 million (92% indirect costs) for Bulimia Nervosa for a total of €319 million annually (Krauth, 2002; Simon et al., 2005). Clearly, indirect costs far exceed healthcare costs and must be included to accu- rately estimate the overall economic burden of eating disorders.

A challenge in understanding the cost of eating disorders is that these disorders are frequently under-diagnosed and under-treated in current healthcare systems. Under-recognition will limit healthcare cost estimates for the disorders, making them significant underestimates. A global review concluded that eating disorders often go unnoticed in primary care. Notably, people with eating disorders still have higher healthcare utilization for associated symptoms even if their disorders remain undiagnosed and they do not pay for direct treatment costs (Si- mon et al., 2005). For example, a nationally representative study in the United States found that the majority of adolescents with an eating disorder engage in health services for emotional or behavioral problems, even if most do not directly discuss their eating or weight concerns (Swanson et al., 2011). A more recent review through 2010 corroborated the underestimates by noting that most studies do not include all associated costs beyond the intervention, especially indirect costs (Stuhldreher et al., 2012).

An important aspect of calculating economic burden is assessing the impact on quality of life, which reflects the degree to which persons enjoy and find satisfaction with their lives. Illnesses, their symptoms, co-morbidities, treatments, and side effects all impact this perception of well-being (i.e. health-related quality of life). Specifically, persons across all types of eating disorders report poorer health-related quality of life compared to the general population, especially on mental components (relative to physical components). While health-related quality of life does improve with treatment and the reduction of eating disorder symptoms, more research is needed to ascertain which aspects of treatment con-

196 Eating Disorders tribute to these improvements (e.g., Hay & Mond, 2005; Baiano et al., 2014). Ef- fective treatments with substantial quality of life benefits can contribute to the overall cost-effectiveness of otherwise seemingly costly treatment options.

CLINICALLY EFFECTIVE INTERVENTIONS Recommended treatment guidelines for eating disorders include nutritional rehabilitation, psychosocial interventions, and medication, although psychosocial interventions are most common. Recommended medications, usually combined with psychosocial interventions, include selective serotonin reuptake inhibitors (SSRIs) for both Anorexia and Bulimia, bupropion for Anorexia, and tricyclic antidepressants for Bulimia. No medications have been approved for adolescents.

Eating Disorders in Adolescents For Anorexia, inpatient treatment, which places the child in a controlled food environment, is relatively common but has not consistently shown clinical effectiveness, especially compared to outpatient treatments. For outpatient treatment, Family-Based Treatments that focus on retraining both family members and the young person on how to address and react to eating behaviors and encourage regular eating patterns are clinically effective for Anorexia; additionally, they are more effective than Interpersonal Therapy (IPT) or Supportive Therapy. For Bu- limia, relatively few treatments have been tested in adolescents and there are no adolescent-specific recommendations. The most evidence-based treatments are Cognitive Behavioral Therapy (CBT) and antidepressants, although some evidence suggests Family-Based Treatments are also effective. A pilot study reviewed here indicated a CBT-based self-care intervention might also be effective (Schmidt et al., 2007). There are no data on the treatment of Binge Eating Disor- der in adolescents, and no cost-effectiveness trials for IPT or Supportive Therapy.

Eating Disorders in Adults For adults, no single treatment has been identified as clinically superior for Ano- rexia, although clinical guidelines recommend Cognitive Behavioral Therapy (CBT), Interpersonal Therapy (IPT), and/or Psychodynamic Therapy. For Bulim- ia and Binge Eating Disorder, both CBT and IPT are clinically effective, and CBT is currently the most commonly recommended treatment for both disorders. CBT focuses on getting the person not to skip meals or restrict their food choices, and instead eat a regular diet with frequent planned meals and snacks. The treatment also works on changing thought patterns that encourage binging and purging, and teaches problem-solving skills to address issues that drive binge eating. IPT focuses less on eating and more on interpersonal interactions that lead to stress and altered eating patterns. Treatment works to improve interactions and reactions to social situations. Finally, Internet-adapted CBT delivery and CBT-based self-help programs are promising avenues of further research. No cost- effectiveness trials are currently available for IPT or Psychodynamic Therapy.

COST-EFFECTIVENESS OF INTERVENTIONS To date, very few randomized controlled trials of the cost-effectiveness of behavioral interventions for eating disorders have been published. We only identified two for adolescents and four for adults. The most recent review of cost-of-illness and cost-effectiveness studies for eating disorders determined that the vast het-

197 Eating Disorders erogeneity of design and methodology and limited assessment of the robustness of the findings make any conclusions difficult (Stuhldreher et al., 2012). Fortu- nately, it is an active area of research with at least three additional studies un- derway. These ongoing studies include: one on a guided self-help intervention for Anorexia; a comparison of a Family-Based Treatment (adapted for adults) and specialist support management for Anorexia; and a comparison of Internet- based Cognitive Behavioral Therapy (CBT) and traditional CBT for Bulimia (Crow et al., 2014).

Eating Disorders in Adolescents One study on Anorexia Nervosa and one study on Bulimia Nervosa compared common treatment strategies for adolescents in the United Kingdom.

Anorexia Nervosa For Anorexia, three treatment modalities were compared: in-patient psychiatric treatment; specialist outpatient treatment including Cognitive Behavioral Thera- py (CBT), parental involvement, and dietary therapy; and general outpatient treatment as usual. Neither clinical outcomes nor total costs were significantly different between the three options after two years; however, specialist outpatient treatment had the lowest costs per person (£26,738) followed by inpatient psychiatric treatment (£34,531) and then general outpatient treatment (£40,794). Based on incremental improvements on an outcome measure (Morgan–Russell Average Outcome Scale), specialist outpatient treatment had a 78% likelihood of being the most cost-effective option (Byford et al., 2007; Gowers et al., 2007).

Bulimia and Eating Disorders Not Otherwise Specified For Bulimia and Eating Disorders Not Otherwise Specified, Family Therapy was compared to Cognitive Behavioral Therapy (CBT)-guided self-care supported by a health professional. CBT-guided self-care had a higher rate of abstinence from binging at six months, but that difference was not observed for binging and purging combined, nor was it maintained at 12 months. Likewise, CBT-guided self-care had significantly lower treatment costs at six months (£245.63 versus £409.35), but that difference was not observed for any other costs nor maintained at 12 months. Overall, CBT-guided self-care might have a slight advantage at treatment end (6 months) but there were no significant differences in clinical efficacy or total costs after 12 months, suggesting both options were equally cost- effective (Schmidt et al., 2007), but should be compared to usual care.

Table 1. Behavioral Interventions for Eating Disorders in Adolescents Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Anorexia Nervosa Byford et al. 167 adoles- Interventions: Morgan– PP: Societal (2007) & cents (age 12- (1) In-patient Russell Aver- Gowers et al. 18 years) with psychiatric age Outcome Total Costs (2007) Anorexia treatment us- Scale (per person):

Nervosa in ing multidis- (MRAOS; ad- I1: £200434,531 Comparing UK. 57 in in- ciplinary psy- justed for ado- (52,439)

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness three treat- tervention #1, chiatric ap- lescents): I2: £200426,738 ment strate- 55 in interven- proach for 6 I1: 8.3 (2.6) (46,809) gies for Ano- tion #2, and weeks, ex- I2: 8.4 (2.4) C: £200440,794 rexia Nervosa 55 in control. tended as in- C: 8.3 (2.6) (63,652) in adolescents dicated. (NS) (NS) (Treatment (2) Specialist Outcome for outpatient d1: 0 Willingness to Child and ad- treatment d2: .040 pay threshold: olescent Ano- with individ- d3 (I1 vs. I2): If value is rexia Nervosa ual Cognitive .040 £0/1-point TOuCAN Tri- Behavioral improvement al) Therapy, par- in MRAOS, ent counseling 78% probabil- with partici- ity specialist pant, dietary outpatient therapy, and services most multi-modal cost-effective, feedback. 16% in-patient services, 6% Control: treatment as General out- usual. As val- patient treat- ue increases, ment as usual. decreases to ~47% for spe- Measures: cialist outpa- 2 years tient services, but still higher than other two options. Bulimia Nervosa & Eating Disorders Not Otherwise Specified Schmidt et al. 47 adolescents Interventions: Percent Ab- PP: Public (2007) (age 13-20 (1) Family stinence from Sector years) with Therapy for Binging and Family Ther- Bulimia Ner- Bulimia Ner- Purging: Total Costs apy vs. Cogni- vosa or Eating vosa. 2 indi- I1: 41.4% (for patients): tive Behavior- Disorder Not vidual ses- I2: 36.0% I1: £320.25 al Therapy- Otherwise sions plus up (NS) (469.52) guided self- Specified in to 13 sessions I2: £437.32* care for ado- UK. 29 in in- with close BMI: (725.63) lescents with tervention #1, others over 6 I1: 21.7 (3.5) (NS) Bulimia Ner- 25 in interven- months. I2: 20.5 (2.0) vosa or Eating tion #2. *1 patient ex- Disorder Not (2) Individual d: .436 cluded due to Otherwise Cognitive Be- extended hospi- Specified havioral Day of Strict talization for Therapy- Dieting (per drug overdose

199 Eating Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness guided self- week): not directly re- care support- I1: 1.7 (3.0) lated to bulim- ed by a health I2: 1.6 (3.0) ia. Otherwise, professional total costs for 10 weekly d: 0 would be sessions, 3 £2,330.04 monthly fol- Day of Fasting (9,490). low-up ses- (per week): sions, and 2 I1: .8 (1.6) Lost Em- optional ses- I2: .4 (1.5) ployment: sions with I: £57.77 close others d: .258 (149.75) over 6 C: £31.44 months. Food-Related (55.14) Fear and Dis- Measures: gust: Family Out- 12-month fol- I1: 1.9 (1.7) of-Pocket Ex- low-up I2: 1.7 (1.8) penses: Lower is better. I: £6.67 (30.55) C: £0 d: .114 Patient Out- Food-Related of-Pocket Ex- Preoccupa- penses: tion: I: £112.57 I1: .8 (.8) (214.60) I2: .7 (.9) C: £92.40 (228.82) d: .118

Eating Disorders in Adults As of 2014, there were no cost-effectiveness studies for the behavioral treatment of Anorexia Nervosa in adults, only three trials for the treatment of Bulimia Ner- vosa, and one for Binge Eating Disorder. All four trials are based on Cognitive Behavioral Therapy (CBT), with one comparison to medication and the rest between different CBT delivery modalities.

Bulimia Nervosa For Bulimia Nervosa, all trials were limited to women and used the same cost- effectiveness measure of the incremental cost per additional abstinent woman. However, as there are currently no standardized willingness to pay thresholds for the societal value of abstinence or methods of converting these clinical outcomes to QALYs, we cannot ascertain overall cost-effectiveness.

A small, older study comparing CBT and medication (tricyclic antidepressant desipramine) found the 24-week course of desipramine alone was the most cost-

200 Eating Disorders effective option after one year compared to a 16-week course of desipramine alone, CBT alone, and the combination of 16-week and 24-week courses of desipramine with CBT (Koran et al., 1995). More recently, two studies from the same set of researchers compared delivery modalities of CBT; in both cases, the novel delivery modality was more cost-effective than traditional CBT delivery.

For Bulimia Nervosa or subsyndromal symptoms, traditional face-to-face CBT was more effective and more expensive than telehealth-based CBT after a year. There was 21.1% likelihood that telehealth CBT was dominant (more effective and less costly), and 78.9% likelihood that telehealth CBT was less effective but also less costly (Crow et al., 2009b; Mitchell et al., 2008). Overall, this suggests that telehealth-based CBT could be the more cost-effective option.

Similarly, compared to traditional face-to-face CBT, stepped care treatment utilizing CBT-based self-help that moved from less intensive and expensive interventions to more intensive and expensive interventions as needed had an 81% likelihood of dominating as more clinically effective and less expensive in terms of direct medical costs after a year. Notably, both treatments were augmented with the selective serotonin reuptake inhibitor (antidepressant medication) fluoxetine as indicated (Crow et al., 2013; Mitchell et al., 2011). However, both telehealth and stepped care CBT-based treatments still need to be compared to usual care to ascertain overall cost-effectiveness.

Binge Eating Disorder For adults with recurrent Binge Eating Disorder, the addition of a CBT-guided self-help intervention with therapist support to treatment as usual led to significantly more binge-free days (BFDs) compared to treatment as usual alone after a year. CBT-guided self-help was cost-saving at $26,847 saved per QALY or $20 saved per BFD. If the value were $40 per BFD, it was 90% likely to be cost- effective, and if the value were $100 per BFD, it increased to 98% likely to be cost- effective (Lynch et al., 2010).

Table 2. Behavioral Interventions for Eating Disorders in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Bulimia Nervosa Crow et al. 293 women Interventions: Eating Disor- PP: (2013) & with Bulimia (1) Stepped der Examina- Healthcare Mitchell et al. Nervosa. 146 care treatment tion (EDE): (2011) in interven- (moves from I1: 1.9 (1.4) ICER (per ab- tion, 147 in less intensive I2: 2.0 (1.9) stinent wom- Stepped care control. and expensive an): treatment vs. to more inten- d: .061 I1: $200512,146 Cognitive Be- sive and ex- I2: $200520,317 havioral pensive if Percent Ab- Therapy for needed) with stinence: 81% probabil- Bulimia Ner- Cognitive Be- I1: 26% ity stepped care vosa havioral I2: 18% treatment with

201 Eating Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Therapy- Cognitive Be- based self- havioral Thera- help for eight py-based self- 20-minute Percent Re- help dominates sessions over mission: high intensity first 20 weeks. I: 32% Cognitive Be- (2) High in- I2: 44% havioral Thera- tensity Cogni- py. tive Behavior- al Therapy for eighteen 50- minute sessions over 4 months.

Augmented with fluoxetine as needed.

Measures: 1-year follow- up Crow et al. 128 women Interventions: Eating Disor- PP: Societal (2009b) & with Bulimia (1) Telemedi- der Examina- Mitchell et al. Nervosa or cine Cognitive tion (EDE) ICER (per ab- (2008) subsyndromal Behavioral Subscales: stinent wom- variants. 62 in Therapy for Restraint an):

Cognitive Be- intervention, 20 sessions I1: 1.8 (1.5) I1: $20087,300 havioral 66 in control. over 16 I2: 1.6 (1.5) I2: $20089,325 Therapy de- weeks. d: −.133 21.1% probabil- livered via ity telemedicine telemedicine (2) Face-to- Eating con- Cognitive Be- vs. face-to- face Cognitive cerns havioral Thera- face for Bu- Behavioral I: .9 (1.3) py dominates limia Nervosa Therapy for C: .6 (1.0) face-to-face 20 sessions d: −.261 Cognitive Be- over 16 havioral Thera- weeks. Shape concerns py, and 78.9% I1: 2.1 (1.6) probability less Measures: I2: 1.8 (1.2) effective but 12-month fol- d: −.214 also less costly. low-up Weight concerns I1: 2.1 (1.5) I2: 1.8 (1.2)

202 Eating Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness d: −.222

Percent Ab- stinence: I1: 22.6% I2: 28.8% Koran et al. 61 women Interventions: Percent Ab- PP: Treatment (1995) (age 18-65 (1) Cognitive stinence: years) with Behavioral I1: 11% (48) ICER (per ab- Comparing Bulimia Ner- Therapy I2: 3% (25) stinent wom- five treat- vosa. 22 in in- (CBT) for 15 I3: 6% (50) an): ments for Bu- tervention #1, weekly ses- I4: 4% (33) I1: $3,230 limia Nervosa 10 in interven- sions then 3 I5: 6% (50) I2: $3,117 tion #2, 10 in monthly ses- I3: $1,982 intervention sions. I4: $6,613 #3, 10 in in- (2) Medication I5: $4,832 tervention #4, (desipramine) and 9 in inter- for 16 weeks. vention #5. (3) Medication (desipramine) for 24 weeks. (4) CBT plus medication for 16 weeks (I1+I2). (5) CBT plus medication for 24 weeks (I1+I3).

Measures: 1 year Binge Eating Disorder Lynch et al. 123 adults Intervention: Binge-Free PP: Societal (2010) with recurrent Treatment as Days (BFDs): Binge Eating usual plus I: 330.7 (41.0) ICER (per Cognitive Be- Disorder. Cognitive Be- C: 305.5 (60.3) QALY): havioral 91.9% female. havioral (p=.002) −$200626,847 Therapy- 59 in interven- Therapy- (95% CI, guided self- tion, 64 in guided self- d: .497 −312,835 to help interven- control. help interven- 38,085) tion for Binge tion. Includes Eating Disor- one 60-minute ICER (per der intro session, BFD):

and 7 addi- −$200620.23 tional 20-25- (95% CI,

203 Eating Disorders

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness minute coach- −154.06 to ing sessions 113.61) with therapist. Average cost Willingness to $167/patient. pay threshold: If value is Control: $40/BFD, 90% Treatment as probability usual. self-help intervention Measures: more cost- 12-month fol- effective than low-up treatment as usual. If value is $100, 98% probability more cost- effective.

LIMITATIONS AND FUTURE DIRECTIONS In addition to the overall need for more clinical and cost-effectiveness trials from which to draw meaningful conclusions, there are some areas that would specifically benefit from additional research. While single studies for any diagnosis are insufficient, there are no randomized controlled trials at all with cost- effectiveness data for Binge Eating Disorder in adolescents, for Anorexia in adults, or for Eating Disorders Not Otherwise Specified in adults.

Given that eating disorders most commonly start in adolescence or early adulthood, it is particularly important to develop interventions for these populations. Most importantly, given that many interventions appear to only produce small benefits and are not effective for many patients, on-going development of new interventions for eating disorders is crucial. Studies for longer durations are needed to measure chronicity, treatment-resistance, and relapse, which will have implications for long-term efficacy, quality of life, and economic burden.

Trials that include Eating Disorders Not Otherwise Specified as well as subsyndromal symptoms will reveal how conditions that do not meet full diagnostic criteria impact the overall economic burden of disordered eating. This is particularly relevant given that Eating Disorders Not Otherwise Specified occur more frequently than both Anorexia and Bulimia combined. Trials that include men are also needed. While most studies focus on females due to higher prevalence of eating disorders, additional data on unique treatment and cost effects for men will also be valuable. The societal stereotype that eating disorders are limited to females will likely perpetuate under-diagnosis and under-treatment in males.

204 Eating Disorders

Finally, cost-effectiveness studies for eating disorders are limited by lack of standardization of outcome measurements. While some studies include similar outcomes such as the cost per binge-free day or per additional abstinent individual, no societal value has been established for these outcomes. Trials should either include outcomes in QALYs or else establish willingness to pay thresholds for common outcomes so that results can be compared with each other. Stand- ardization will also allow comparison to treatment of other clinical conditions, which is especially relevant given that treatment for eating disorders is not widely available and encouraged in most healthcare systems. Cost-effectiveness data for behavioral interventions for eating disorders may make a compelling case to develop new treatments and expand access to available ones.

KEY POINTS • Insufficient data is available to draw cost-effectiveness conclusions for behavioral interventions for both adolescents and adults.

Eating Disorders in Adolescents • For Anorexia, specialist outpatient treatment including Cognitive Behavioral Therapy, parental involvement, and dietary therapy had a 78% likelihood of being more cost-effective than standard inpatient or outpatient treatment based on incremental improvements on an outcome measure after two years.

• For Bulimia and Eating Disorders Not Otherwise Specified, Cognitive Behav- ioral Therapy-guided self-help supported by a health professional had some clinical and cost advantages over Family Therapy at six months but those differences were gone at 12 months, suggesting the two interventions were similarly cost-effective to each other but should be compared to usual care.

• For Binge Eating Disorder, no studies were available.

Eating Disorders in Adults • For Bulimia in women after a year, antidepressant medication may be relatively more cost-effective than in-person Cognitive Behavioral Therapy (CBT). Also, lower-intensity delivery mechanisms (telehealth, stepped care) of CBT were more cost-effective than high-intensity, face-to-face CBT. How- ever, low-intensity delivery mechanisms of CBT were not compared directly to medication and none of the treatments were compared to usual care.

• For recurrent Binge Eating Disorder, adding CBT-guided self-help with therapist support to treatment as usual was cost-saving at $26,847 saved per QALY or $20 saved per binge-free day after a year.

• For Anorexia and Eating Disorders Not Otherwise Specified, no studies were available

205 Eating Disorders

REFERENCES Agras WS. The consequences and costs of the eating disorders. Psychiatr Clin North Am. 2001 Jun;24(2):371-9.

Baiano M, Salvo P, Righetti P, Cereser L, Baldissera E, Camponogara I, Balestrieri M. Exploring health-related quality of life in eating disorders by a cross-sectional study and a comprehensive review. BMC Psychiatry. 2014 Jun 4;14:165.

Byford S, Barrett B, Roberts C, Clark A, Edwards V, Smethurst N, Gowers SG. Economic evaluation of a randomised controlled trial for anorexia nervosa in adolescents. Br J Psychiatry. 2007 Nov;191:436-40.

Crow S. The economics of eating disorder treatment. Curr Psychiatry Rep. 2014 Jul;16(7):454.

Crow SJ, Agras WS, Halmi KA, Fairburn CG, Mitchell JE, Nyman JA. A cost effectiveness analysis of stepped care treatment for bulimia nervosa. Int J Eat Dis- ord. 2013 May;46(4):302-7.

Crow SJ, Mitchell JE, Crosby RD, Swanson SA, Wonderlich S, Lancanster K. The cost effectiveness of cognitive behavioral therapy for bulimia nervosa delivered via telemedicine versus face-to-face. (2009b). Behav Res Ther. 2009 Jun;47(6):451- 3.

Crow SJ, Peterson CB, Swanson SA, Raymond NC, Specker S, Eckert ED, Mitch- ell JE. Increased mortality in bulimia nervosa and other eating disorders. (2009a). Am J Psychiatry. 2009 Dec;166(12):1342-6.

Gowers SG, Clark A, Roberts C, Griffiths A, Edwards V, Bryan C, Smethurst N, Byford S, Barrett B. Clinical effectiveness of treatments for anorexia nervosa in adolescents: randomised controlled trial. Br J Psychiatry. 2007 Nov;191:427-35.

Hay, PJ, Mond, J. How to ‘count the cost’ and measure burden? A review of health-related quality of life in people with eating disorder. J Ment Health. 2005 Dec;14(6):539-52.

Hudson JI, Hiripi E, Pope HG Jr, Kessler RC. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychia- try. 2007 Feb 1;61(3):348-58.

Koran LM, Agras WS, Rossiter EM, Arnow B, Schneider JA, Telch CF, Raeburn S, Bruce B, Perl M, Kraemer HC. Comparing the cost effectiveness of psychiatric treatments: bulimia nervosa. Psychiatry Res. 1995 Sep 8;58(1):13-21.

Krauth C, Buser K, Vogel H. How high are the costs of eating disorders - anorexia nervosa and bulimia nervosa - for German society? Eur J Health Econ. 2002;3(4):244-50.

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Lynch FL, Striegel-Moore RH, Dickerson JF, Perrin N, Debar L, Wilson GT, Kra- emer HC. Cost-effectiveness of guided self-help treatment for recurrent binge eating. J Consult Clin Psychol. 2010 Jun;78(3):322-33.

Mitchell JE, Agras S, Crow S, Halmi K, Fairburn CG, Bryson S, Kraemer H. Stepped care and cognitive-behavioural therapy for bulimia nervosa: randomised trial. Br J Psychiatry. 2011 May;198(5):391-7.

Mitchell JE, Crosby RD, Wonderlich SA, Crow S, Lancaster K, Simonich H, Swan- Kremeier L, Lysne C, Myers TC. A randomized trial comparing the efficacy of cognitive-behavioral therapy for bulimia nervosa delivered via telemedicine versus face-to-face. Behav Res Ther. 2008 May;46(5):581-92.

Patrick L. Eating disorders: a review of the literature with emphasis on medical complications and clinical nutrition. Altern Med Rev. 2002 Jun;7(3):184-202.

Schmidt U, Lee S, Beecham J, Perkins S, Treasure J, Yi I, Winn S, Robinson P, Murphy R, Keville S, Johnson-Sabine E, Jenkins M, Frost S, Dodge L, Berelowitz M, Eisler I. A randomized controlled trial of family therapy and cognitive behavior therapy guided self-care for adolescents with bulimia nervosa and related disorders. Am J Psychiatry. 2007 Apr;164(4):591-8.

Simon J, Schmidt U, Pilling S. The health service use and cost of eating disorders. Psychol Med. 2005 Nov;35(11):1543-51.

Striegel-Moore RH, Leslie D, Petrill SA, Garvin V, Rosenheck RA. One-year use and cost of inpatient and outpatient services among female and male patients with an eating disorder: evidence from a national database of health insurance claims. Int J Eat Disord. 2000 May;27(4):381-9.

Stuhldreher N, Konnopka A, Wild B, Herzog W, Zipfel S, Löwe B, König HH. Cost-of-illness studies and cost-effectiveness analyses in eating disorders: a systematic review. Int J Eat Disord. 2012 May;45(4):476-91.

Swanson SA, Crow SJ, Le Grange D, Swendsen J, Merikangas KR. Prevalence and correlates of eating disorders in adolescents. Results from the national comorbidity survey replication adolescent supplement. Arch Gen Psychiatry. 2011 Jul;68(7):714-23.

207 Alcohol Use

CHAPTER 8: ALCOHOL USE

ABSTRACT Many Americans surpass guideline recommendations for alcohol consumption, leading to both risky alcohol use and Alcohol Use Disorder. This over consumption of alcohol, in turn, has significant health consequences. Over use of alcohol is a known risk factor for certain cancers, depression, epilepsy, coronary heart disease, hypertension, stroke, and liver cirrhosis, among others. Alcohol Use Disorder (e.g., alcohol dependence and/or abuse) commonly co-occurs with other neuropsychiatric disorders including Drug Use Disorders as well as Anxiety Disorders, Depressive Disorders, Mood Disorders, and Schizophrenia.

The U.S. prevalence of Alcohol Use Disorder was 8.46% in 2002. Further, the economic burden of excessive alcohol use (e.g. binge or heavy drinking, alcohol consumption by youth or pregnant women) was estimated at $223.5 billion in 2006. In adolescents, school-based family-focused preventive skills training programs appeared to have long-term cost benefits for both families and society. Motiva- tional Interviewing was also cost-effective in reducing alcohol use. Motivational Interviewing was particularly cost-effective when provided in combination with personalized Normative Feedback (i.e. data on their alcohol use compared to population patterns), and when provided to male populations. For adolescents who used alcohol, cannabis, or both, a combination of Motivational Enhance- ment Therapy and Cognitive Behavioral Therapy was more cost-effective than Chestnut’s Bloomington Outpatient Treatment (designed to increase desire to change and provide necessary skills), and more cost-effective without the addition of Assertive Continuing Care (home-based care).

Studies of Motivational Interviewing in adults targeted two main populations: 1) those in the general public who were screened for risky alcohol use, and 2) those actively seeking treatment to decrease or stop their alcohol use. For adults screened in emergency rooms (ER), interventions, including Normative Feedback seemed cost-effective when limited to those with alcohol-related ER incidents, and Brief Behavioral Counseling seemed more cost-effective than Patient Educa- tion, including up to four years later. However, for adults with excessive alcohol use identified in sexual health clinics, Brief Advice was less cost-effective. For adults seeking treatment, shorter therapies with fewer components seemed more cost-effective: Brief Intervention limited to one session was more cost-effective than Cognitive Behavioral Therapy, and individual alcohol counseling alone was more cost-effective than adding Behavioral Couples Therapy. Motivational En- hancement Therapy and Social Behavior and Network Therapy were both considered cost-effective in terms of overall public sector costs but were not compared to usual care or no intervention; cost-effectiveness between the two varied depending on the willingness to pay threshold, with lower thresholds favoring Social Behavior and Network Therapy and higher thresholds favoring Motiva- tional Enhancement Therapy. In one comparison of medication and behavioral intervention alone or in combination with each other, none of the options including behavioral interventions were cost-effective. Lastly, for Internet-based self- help treatments with or without a therapist, the self-help modules plus therapist were more cost-effective than self-help alone.

208 Alcohol Use

It is clear that excessive alcohol use is a problem for both adolescents and adults, and available data support some cost-effective prevention and treatment behavioral interventions that can be easily implemented within limited time and resources.

BACKGROUND ON EXCESSIVE ALCOHOL USE Alcohol overuse is a serious public health issue in the United States, and considered the third-leading preventable cause of death after smoking and high blood pressure. Recommendations for ideal alcohol use include 1) complete abstinence or 2) less than one drink per day for women or two drinks per day for men (not to exceed 14 drinks per week total). Recommendations also include complete abstinence under the age of 21 years and during pregnancy. These recommendations vary for people with specific risk factors or health conditions (e.g., young or old age, chronic disease, acute illness, medications, mental health problems, sleep problems, poor diet, and family history of alcohol or drug use problems).

Importantly, the measure of a “standard” drink is 18 milliliters of pure alcohol. Typical servings of alcohol often exceed this “standard” drink size, commonly leading to underestimates of alcohol consumption. For instance, a pint of 5% beer (e.g., Budweiser, Coors) is 1.3 standard drinks. For higher alcohol content beer, this can increase to the equivalent of more than two standard drinks, or more than the daily amount recommended for men and more than double the daily amount recommended for women. Likewise, a 750-milliliter bottle of 12% wine equals five standard drinks. In other words, it should take five women or 2.5 men to consume a typical bottle of wine over dinner.

Excessive alcohol use can cause both immediate and future health risks. The short-term risks have three main causes: coordination impairment, amplification of emotions and impulsivity, and alcohol poisoning. Alcohol use is also a risk factor for injury and chronic conditions. A meta-analysis found that the volume of alcohol consumed was associated with increased risk for all diseases studied including multiple cancers, depression, epilepsy, coronary heart disease, hypertension, stroke, and liver cirrhosis. Conversely, some patterns of controlled alcohol consumption have shown beneficial effects on coronary heart disease, stroke, and diabetes (Rehm et al., 2003). Finally, alcohol use in young people is associated with continued risky usage into adulthood, alcohol abuse, and academic problems or other risky behaviors, while alcohol use during pregnancy increases the risk of infertility, miscarriage, stillbirth, and premature delivery as well as increases the likelihood for Fetal Alcohol Spectrum Disorders.

Alcohol Use Disorder In addition to general health concerns of alcohol overuse, Alcohol Use Disorder is an official classification of the Diagnostic and Statistical Manual of Mental Dis- orders (DSM–5). This diagnosis targets recurrent alcohol use (especially in excess of one’s own intentions) despite negative consequences and oftentimes with a desire to decrease or quit use. In prior editions of the DSM, this diagnosis was subdivided into Alcohol Abuse and Alcohol Dependence:

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• Alcohol Abuse included repeated alcohol use with negative consequences (e.g., poor work performance, absence from school, neglect of household, or social and interpersonal problems (e.g., arguments with spouse)) or hazardous behaviors, like operating a car, after alcohol use. • Alcohol Dependence included tolerance (e.g., same amount of alcohol has less effect or conversely requires more alcohol to have same effect) and withdrawal (e.g., experience negative symptoms in the absence of alcohol or require alcohol to alleviate the symptoms).

The updated definition of Alcohol Use Disorder includes any combination of the Abuse and Dependence symptoms. However, much of the available data from earlier studies remains divided into Abuse and Dependence.

PREVALENCE OF EXCESSIVE ALCOHOL USE Likelihood of alcohol overuse increases during adolescence and peaks in young people age 21 to 25 years. Among young people, 33.3% of 18 to 20 year olds and 45.5% of 21 to 25 year olds reported binge alcohol use (i.e. five or more drinks in a single occasion in the previous 30 days) as of 2010 (SAMHSA, 2011). While the prevalence of excessive alcohol use in the U.S. adult population was not available, the prevalence of Alcohol Use Disorder was 8.46% (17.6 million people) as of 2002, based on Alcohol Abuse in 4.65% (9.7 million people) and Alcohol Depend- ence in 3.81% (7.9 million people). In general, Alcohol Use Disorder is more common in men than women and decreases with age (Grant et al., 2004).

Alcohol Use Disorder frequently co-occurs with other neuropsychiatric disorders including other Drug Use Disorders. The prevalence of dual Alcohol Use Disor- der and Drug Use Disorder is only 1.1% (2.3 million people), but the conditional prevalence of someone with Alcohol Use Disorder also having Drug Use Disor- der is 13% and of someone with Drug Use Disorder also having Alcohol Use Disorder exceeds 50% (Stinson et al., 2005). Furthermore, for those with Alcohol Dependence, 36.9% have a comorbid Anxiety Disorder, 29.2% Mood Disorder, 29.9% Major Depressive Disorder, and 24% Schizophrenia. These same patterns parallel those with Alcohol Abuse, with 29.1% Anxiety Disorder, 12.3% Mood Disorder, 11.3% Major Depressive Disorder, and 9.7% Schizophrenia, all of which are higher than in the general population (Petrakis et al., 2002).

ECONOMIC BURDEN OF EXCESSIVE ALCOHOL USE The economic burden of excessive alcohol use (i.e. binge drinking more than four to five drinks per occasion, heavy drinking more than one to two drinks per day, and alcohol consumption by youth or pregnant women) in the United States was estimated at $223.5 billion as of 2006, of which more than 70% ($161.3 billion) was due to lost productivity. Moreover, 75% ($170.7 billion) was due specifically to binge drinking. Meanwhile, underage drinking cost $27 billion, drinking during pregnancy cost $5.2 billion, and crime attributed to alcohol use cost $73.3 billion (Bouchery et al., 2011). This is corroborated by earlier estimates of annual costs at $184.8 billion in 1998, inflated to $265 billion in 2006 (Harwood, 1998; Bouchery et al., 2011). Alcohol is unique in that some cost estimates could in-

210 Alcohol Use clude economic benefits due to potential positive health effects of limited alcohol use; the above estimates do not.

CLINICALLY EFFECTIVE INTERVENTIONS Clinical recommendations for risky alcohol use begin with prevention, early detection and brief intervention. More intensive psychotherapies as well as pharmacotherapy are recommended if risky alcohol use continues and for Alcohol Use Disorder.

Early Detection and Initial Treatment General recommendations start with screening for risky alcohol use in primary care and providing Behavioral Counseling and Patient Education if needed. Be- havioral Counseling is an umbrella term and can vary greatly, although often comprises brief session(s), with multiple six to 15 minute sessions demonstrating the greatest clinical effectiveness to date. This counseling can include different elements such as cognitive behavioral strategies, problem-solving, or stress management, and can be provided face-to-face, via telephone, or via a computer or the Internet. Patient Education can also vary, but a common tool in the studies reviewed was to provide an informational brochure or pamphlet. In some cases, tailored/personalized Normative Feedback, in which individuals receive data about how their alcohol use compares with a larger population, was also provided in-person or mailed directly to the individual.

A review of reviews of Brief Interventions (including Brief Counseling and Pa- tient Education) for alcohol use in primary care concluded that they are clinically effective, although some components may be more effective than others (O’Donnell et al., 2014). Importantly, while screening may identify persons along the entire spectrum of alcohol misuse, Brief Interventions are not likely to be sufficient for Alcohol Use Disorder (see below).

Alcohol Use in Adolescents and Young Adults As described earlier, early alcohol use can have lifelong adverse consequences, underlining the importance of early interventions for adolescents and young adults. Brief Interventions (typically lasting 1-2 sessions) are the standard recommendation. A review of almost 200 Brief Interventions aimed at motivating behavior change in adolescents (age 11 to 18 years) and young adults (age 19 to 30 years) who were not seeking treatment found they were effective at decreasing alcohol consumption and alcohol-related problems in both age groups for up to a year (Tanner-Smith et al., 2015). Another review of Brief Interventions specifically for young people (up to age 21) who visit the emergency room with alcohol-related problems concluded data were inconclusive about the effectiveness of Brief Interventions for both alcohol and drug-related problems (Newton et al., 2013).

Additionally, many interventions focus on college students, considering college age as a time of transition and changes in alcohol use. A review of behavioral interventions specifically targeting alcohol use amongst first-year college students concluded that interventions were effective in reducing alcohol consumption and alcohol-related problems. These interventions, most of which lasted a single ses-

211 Alcohol Use sion and could be classified as Brief Interventions, included Normative Feed- back, Moderation Strategies, Expectancy Challenge, Identification of Risky Situa- tions, and Goal Setting. The most effective ones included Normative Feedback, Identification of Risky Situations, and Goal Setting (Scott-Sheldon et al., 2014).

Alcohol Use Disorder Recommendations for Alcohol Use Disorder can include pharmacology and/or psychotherapy, although medication is typically only used to treat specific symptoms (e.g., withdrawal) or as adjunctive treatment, while psychosocial interventions can be integral to decreasing or quitting use. Clinically effective psychosocial interventions include Motivational Enhancement Therapy, Cognitive Behav- ioral Therapy, Behavioral Therapies, Twelve-Step Facilitation Therapy, Marital and Family Therapies, Group Therapies, Psychodynamic Therapy, and Interper- sonal Therapy. However, cost-effectiveness data are only available for a few.

Motivational Interviewing helps individuals identify their ambivalence, generate internal motivations, set goals, and promote behavior change. Motivational En- hancement Therapy is a version of Motivational Interviewing designed specifically for substance use that utilizes these techniques to develop internal motivation to quit the addiction and achieve other life goals. Cognitive Behavioral Ther- apy helps the individual identify and overcome negative thoughts and behaviors. CBT for alcohol disorders include developing skills to promote self-control, prevent relapse, and engage in effective coping strategies during the process of quitting alcohol use. It can be useful to plan in advance for times when self- control may be more difficult (e.g., cravings, environments when others are engaging in alcohol use).

In general, twelve-step peer-based self-help groups such as Alcoholic Anony- mous are helpful for persons with substance dependence or abuse. Twelve-Step Facilitation (TSF) Therapy utilizes the same principles as these programs in individual or group settings, and focuses on the same core themes such as accepting the need for abstinence and surrendering to full participation in the treatment. Marital and Family Therapies can involve family members of the affected individual. For instance, Behavioral Couples Therapy includes both the alcohol-using person and their partner. In addition to the individual counseling sessions for the alcohol-using person, this joint therapy includes a contract to abstain from alcohol use, homework assignments, behavioral rehearsal, and communication skills.

COST-EFFECTIVENESS OF INTERVENTIONS Briefly, it is worth noting that cost-effective public health interventions for alcohol use exist at the population level (e.g., regulating alcohol price and availability, banning alcohol advertising, legislating alcohol-related harm such as driving under the influence), but in this chapter we focus on changes at the individual level.

Two reviews of brief interventions (e.g., screening, counseling) in primary care) concluded they are cost-effective for risky alcohol use, and more cost-effective than comparable preventive services for other health outcomes. By one estimate, Brief Screening and Counseling cost $1,755 per QALY from the healthcare per-

212 Alcohol Use spective and was cost-saving from a societal perspective (Angus et al., 2014; Sol- berg et al., 2008). A meta-analysis of single-session Normative Feedback outside of primary care (without therapeutic support) concluded it was probably cost- effective given its efficacy and the minimal time and financial investments needed to implement it (Riper et al., 2009).

Alcohol Use in Adolescents and Young Adults One study looked at school-wide family-focused preventive skills training to reduce the risk of Alcohol Use Disorder for families of sixth graders, projecting the number of cases prevented based on the number of Alcohol Use Disorders after four years. Two different programs on parenting skills, the Iowa Strengthening Families Program with interactive sessions of parents and children together and Preparing for the Drug Free Years focused primarily on parents, were projected to have fewer cases of Alcohol Use Disorders over their lifetime and therefore less societal costs compared to no intervention. Specifically, it was estimated to cost $12,459 per case prevented in the Iowa Strengthening Families Program and $20,439 per case prevented in the Preparing for the Drug Free Years program, with a net benefit per family of $3,923 in the former and $2,697 in the latter (Spoth et al., 2002).

Motivational Interviewing was cost-effective in decreasing alcohol use in young people with prior excessive alcohol use, particularly adolescent males and college freshman. In children and adolescents (age 9 to 19) who ended up in the emergency room due to alcohol use, Motivational Interviewing was more cost- effective than standard care (i.e. brief advice about alcohol use) after six months. Motivational Interviewing was more clinically effective on every measure and only cost $8,795 per QALY, within typical willingness to pay thresholds. Nota- bly, this cost-effectiveness was much better for males at $2,414 per QALY, which likely drove overall cost-effectiveness as it actually was not cost-effective for females alone at $121,469 per QALY (Neighbors et al., 2010; Monti et al., 1999).

In college freshman (99% under age 20) who were screened for a recent episode of heavy drinking in the past two weeks, both a single session of Motivational Interviewing or an automated Normative Feedback email were dominated by no intervention. However, combining Motivational Interviewing and Normative Feedback had the potential to be cost-effective after three months: If a decrease of one drink per drinking episode was valued at more than $47 per student, then the combined intervention had up to 80% likelihood of being more cost-effective, and if a decrease in one less heavy drinking day (five or more drinks for men, four or more drinks for women) was valued at more than $64 per student, then the combined intervention had up to 75% likelihood of being more cost-effective. Overall, not intervening was least expensive and least effective, while the combined intervention was most expensive and most effective, with cost- effectiveness depending on the value of each improvement (Cowell et al., 2012).

Lastly, one study looked at adolescents with Alcohol Use Disorder, Cannabis Use Disorder, or both disorders combined. Chestnut’s Bloomington Outpatient Treatment (CBOP) consists of multiple treatment components designed to increase the desire to change, provide necessary skills, and create an environment

213 Alcohol Use supportive for this change. CBOP was compared against a combination of Moti- vational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). Each treatment was provided either with or without Assertive Continuing Care (ACC; i.e. home-based continuing care). Based on the average cost per day abstinent and per person in recovery after 12 months, MET/CBT without ACC was more cost-effective than MET/CBT with ACC or CBOP with or without ACC at $4.25 per day abstinent or $2,620 per person in recovery at 12 months. However, it was not compared to standard care or no intervention (Godley et al., 2010)

Table 1. Behavioral Interventions for Alcohol Use in Children and Adolescents Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Cowell et al. 656 college Interventions: Mean Effec- PP: University (2012) freshmen (1) Motiva- tiveness for (99% age <20 tional Inter- Decrease in ICER (per Motivational years) with viewing (MI) Average one-drink re- Interviewing recent heavy with a single, Drinks per duction in av- with Norma- drinking at a brief (30-45 Drinking Oc- erage drinks tive Feedback university in minute) coun- casion: per session): to reduce col- U.S. 60% fe- seling session. I1: .286 (.023) I1: Dominated lege drinking male. 165 in $200916.51/ I2: .360 (.022) I2: Dominated intervention student. I3: .769 (.022) I3: $200947.04 #1, 170 in in- (2) Normative C: -.003 (0.024) tervention #2, Feedback ICER (per de- 154 in inter- (NF) automat- Mean Effec- crease in #of vention #3. ically generat- tiveness for heavy drink- ed from base- Decrease in ing sessions): line assess- Number of I1: Dominated ment and Heavy Drink- I2: Dominated

emailed after ing Sessions: I3: $200964.34 1 week. I1: 1.354

$200917.33/stu (0.040) Willingness to dent. I2: 1.475 pay threshold: (3) Motiva- (0.040) For one-drink tional Inter- I3: 1.848 reduction per viewing (MI) (0.044) session, no and Norma- C: 1.288 intervention tive Feedback (0.039) more likely to (NF) com- be cost- bined. No significant effective if

$200936.03/stu differences on value ≤$47 dent. any other and MI plus measure. NF more like- Control: ly to be cost- Assessment effective if only with no >$47. For one intervention. less heavy drinking day,

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Measures: no interven- 3-month fol- tion more low-up likely to be cost-effective if ≤$64 and MI plus NF more likely to be cost-effective if >$64. Godley et al. 320 adoles- Intervention: Percentage of PP: Treatment (2010) cents (age 12- Days Absti- 18 years) with Assertive Con- nent from Al- Average Cost Adolescent Substance Use tinuing Care cohol or Other (per episode): outpatient Disorders in (ACC) is home- Drugs for Past I1a: based care for treatment and U.S. 76% 90 Days: $19975,303.14 continuing male. 73% in- 12-14 weeks. I1a: 81.8% I1b: (1a) Chest- care for Sub- volved in ju- I1b: 78.0% $19973,246.66 stance Use venile justice nut’s Bloom- I2a: 79.3% I2a: ington Outpa- Disorders system. 75% I2b: 85.0% $19973,655.95 Cannabis Use tient Program I2b: (CBOP) to in- Disorder, 49% GAIN’s Sub- $19971,143.89 Alcohol Use crease desire stance Prob- Disorder, 35% to change, lem Scale Average Cost both Cannabis provide nec- (SPS) for Past (per day ab- and Alcohol essary skills, Month: stinent): and create an Use Disor- I1a: 1.2 I1a: $199719.37 environment ders. 80 in in- I1b: 1.68 I1b: $199714.00 supportive for tervention I2a: 1.2 I2a: $199714.97 this change. #1a, 80 in in- I2b: 1.2 I2b: $19974.25 tervention With ACC. #1b, 81 in in- (1b) CBOP No significant Average Cost tervention without ACC. differences in (per person in #2a, 79 in in- (2a) Motiva- clinical care. recovery at 12 tervention tional En- months): #2b. hancement I1a: Therapy and $199713,945.28 Cognitive Be- I1b: havioral $199711,131.42 Therapy I2a: (MET/CBT) $199712,113.57 for 2 individ- I2b: ual sessions, 3 $19972,619.87 group sessions, 2 family Based on cost sessions. With per day absti- ACC. nent and cost

215 Alcohol Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness (2b)MET/CBT per person in without ACC. recovery at 12 months, Measures: MET/CBT 12-month fol- without ACC low-up was the most cost-effective option. Neighbors et In U.S., 94 Intervention: Percentage PP: Societal al. (2010) & youth (age 9- Motivational- Drink and Monti et al. 19 years) ad- Interviewing Drive: ICER (per (1999) mitted to based inter- I: 35.9% QALY): emergency vention for C: 55.9% $8,795 Motivational department one session. (p<.05) Interviewing- for drinking- Average cost Men only based inter- related inju- $169.74- Percentage $2,414 vention in ries and $173.15/ Alcohol- emergency screened for person. Related Inju- Women only department risky alcohol ries: $121,469 use. 64% Control: I: 20.5% male. 52 in Standard care C: 50.0% intervention, (brief advice (p<.01) 42 in control. to stop alcohol-related Percentage risk behav- Vehicular Ci- iors). Average tation: cost $81.04/ I: 13.2% person. C: 29.4% (p<.05) Measures: 6-month fol- Percentage low-up Alcohol- Related Prob- lems: I: 51.2% C: 60.5% (p<.05) Spoth et al. 478 families of Interventions: Projected Life- PP: Societal (2002) 6th graders in (1) Iowa time Alcohol 33 rural Strengthening Use Disorder ICER (per case Family- schools. Ran- Families Pro- Rate: prevented): focused inter- domized by gram, 7- I1: 37.65% I1: $12,459 ventions in school. 162 in session inter- (3.59) I2: $20,439 Alcohol Use intervention vention with I2: 40.46% Disorder pre- #1, 153 in in- parents and (3.74) Benefit-Cost vention in ad- tervention #2, students to- C: 43.17% Ratio:

216 Alcohol Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness olescents 163 in inter- gether. Total (3.68) I1: $9.60 per vention #3. cost $80,562. $1 invested (2) Preparing I2: $5.85 per for the Drug $1 invested Free Years 5- session inter- Net Benefit vention fo- (per family): cused pri- I1: $5,923 marily on I2: $2,697 parents. Total cost $68,903.

Control: No intervention.

Measures: 4 years

Alcohol Use in Adults Interventions for alcohol use in adults typically fall into two categories: 1) for adults in the general population who are screened while receiving healthcare services to determine whether they have high quantity and/or frequency or alcohol use and 2) for adults who are actively seeking treatment for their alcohol use, which can include but is not limited to a diagnosis of Alcohol Use Disorder.

Adults in General Population In studies similar to those for young people visiting the emergency room, three studies looked at adults visiting the emergency room and screened for risky alcohol use. An Australian study compared mailing personalized Normative Feedback to no intervention for people (age 14 and older) who ended up in the emergency room for any reason, but only found differences within the 23% of persons with alcohol-related incidents. Amongst these persons, the intervention decreased alcohol use by more than half and only cost Au$0.48 for an individual to have one less drink each week, as measured after six weeks (Havard et al., 2012).

Information pamphlets alone or combined with single in-person sessions also appeared to be cost-effective for adults visiting emergency rooms with alcohol misuse problems. In the United Kingdom, participants were informed that their level of drinking might be harmful to their health and asked if they would like to receive a brief intervention. Those who agreed received an information pamphlet alone or in combination with a referral for an in-person session with a health worker. Importantly, only 33% of people who received the referral attended the session. Despite this, the referral to the health worker dominated the pamphlet alone at £22 per incremental decrease in weekly alcohol consumption and a

217 Alcohol Use greater than 65% probability of being more cost-effective at all willingness to pay thresholds after one year (Barrett et al., 2006; Crawford et al., 2004).

In the United States, primarily low-income African American and Hispanic adults visiting the emergency room and screened for risky alcohol use also received an information pamphlet alone or combined with Brief Counseling. The latter combined approach included customized action plans depending on the persons “readiness to change” (i.e. how willing they said they were to change their drinking behaviors). Importantly, the majority of costs were due to the screening itself. The additional costs of the Brief Counseling were $135 per patient. Overall, the combined intervention cost $219 per one drink decrease in average number of weekly drinks and $61 per 1% improvement in heavy episodic drinking compared to the informational pamphlet alone after three months, but cost-effectiveness will depend on the willingness to pay threshold for these outcomes (Kunz et al., 2004).

Outside the emergency room, adults screened for risky alcohol use in primary care also found Brief Counseling including Normative Feedback, with emphasis on the need to decrease alcohol use and support for goal development was more cost-effective than usual care (an informational pamphlet). Notably, clinical improvements at six and 12 months mostly persisted at 48 months (e.g., significant reductions in alcohol use, binge drinking episodes, hospitalization, emergency department visits), yet those receiving usual care also reduced their alcohol use over time leading to no significant clinical differences at 48 months. Nonetheless, the incremental net benefit (i.e. cost of the desired health outcome minus the cost of the intervention) of Brief Counseling was positive at $7,780 (Fleming et al., 2002; Fleming et al., 2000; Mundt et al., 2006).

Finally, people attending sexual health clinics also have high levels of alcohol consumption. For patients identified with excessive alcohol use, Brief Advice with feedback on alcohol and health, written information, and an offer to make an appointment with an Alcohol Health Worker had no differences in costs, quality of life, or clinically significant improvements in alcohol use compared to a generic health information leaflet after six months. Brief Advice was less cost- effective than the generic health information leaflet at all willingness to pay thresholds (Crawford et al., 2015).

Table 2. Behavioral Interventions for Alcohol Use for Adults in General Population Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Crawford et 592 people Intervention: Mean Weekly PP: al. (2015) (age 19+ Brief advice Alcohol Con- Healthcare years) who with feedback sumption (in and Social Brief advice attended sex- (2-3 minutes) prior 90 days): Services for excessive ual health on alcohol I: 18.1 (15.6) alcohol con- clinics and and health, C: 20.3 (16.6) ICER (per sumption were drinking written in- d: .137 QALY): among people excessively in formation, Dominated

218 Alcohol Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness attending UK. 301 in in- and offer for a Mean Units sexual health tervention, follow-up ap- per Drinking Total Costs clinics 291 in control. pointment. Day: (per partici- Average cost I: 9.3 (5.3) pant): £12.57/patient C: 10.4 (5.8) I: £319.28 d: .198 C: £310.87 Control: (NS) Leaflet on Percent Days health and Abstinent: lifestyle. I: 70.9% (22.1) C: 70.7% (22.6) Measures: 6-months fol- Percent Un- low-up protected Sex: I: 52.9% C: 59.1% Havard et al. 244 partici- Intervention: Drinks Per PP: Hospital (2012) pants (age 14+ Mailed Per- Week: years; median sonal- Alcohol-related ICER (per 1- Mailed Per- age 29) who ized Feedback ED visit drink reduc- sonalized presented in 5 regarding al- I: 11.9 tion per Feedback for emergency cohol con- C: 24.1 week): risky alcohol departments sumption. (p<.05) Alcohol-related use assessed (ED) in Aus- Average cost ED visit in emergency tralia and Au$5.83/ d: .59 Au$0.48 rooms screened posi- patient. tive for risky alcohol use. Control: 74% male. No feedback 23% alcohol- or contact. related ED visit. 124 in Measures: intervention, 6-week fol- 120 in control. low-up Barrett et al. 290 alcohol Intervention: Mean Weekly PP: Societal (2006) & misusing “Think About Units of Con- Crawford et adult patients Drink” infor- sumption: ICER (per 1- al. (2004) presenting in mational I: 57.2 (68.4) unit reduction a hospital pamphlet C: 70.8 (88.8) in weekly al- Emergency emergency with referral d: .173 cohol con- department room in UK. to alcohol sumption): referral to al- 131 in inter- health worker Mean Units £200222 cohol health vention, 159 who delivers Consumed worker for in control. brief 30-50 Per Drinking Willingness to brief interven- minute inter- Day: pay threshold: tion vention. 33% I: 13.1 (11.1) Dominates at

219 Alcohol Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness attended ses- C: 16.0 (15.6) all values, sion. Average (p=.038) with >65%

cost £200219. d: .217 probability pamphlet plus Mean Propor- referral to al- tion Days Ab- cohol health Control: stinent: worker more “Think About I: 48.0 (33.0) cost-effective Drink” infor- C: 44.6 (35.7) than pam- mational d: .099 phlet alone. pamphlet only. Mean Num- ber of Attend- Measures: ances at Local 12-month fol- ED: low-up I: 1.2 (2.4) C: 1.7 (3.4) (p=.046) d: .172 Fleming et al. 774 adult pa- Intervention: Change in PP: Societal (2002 & 2000) tients (age 18- Brief physi- Frequency of & Mundt 65 years) cian advice Heavier Net Benefit (2006) screened for (e.g., Norma- Drinkers (>20 (cost benefits at-risk alcohol tive Feedback, drinks in men of interven- Brief alcohol consumption alcohol ef- or >13 drinks tion minus intervention across 17 pri- fects, drinking in women in costs of inter- in primary mary care diary cards, prior 7 days): vention): care clinics in U.S. drinking I: 22.4% $19937,780 (95% (Trial for Ear- 392 in inter- agreement) C: 26.4% CI, $894 to ly Alcohol vention, 382 via two 15- (NS) $14,668) Treatment, in control. minute physi- (p=.01) TrEAT) cian visits (1 Change in month apart) Frequency of and two 5- Any Binge Estimates of minute nurse Drinking (>5 cost benefits follow-up drinks in one based on reduc- calls (2 weeks sitting) Per tions in future after visits). Month: emergency I: 63.8% room visits and Control: C: 70.4% hospitalizations Usual care (p<.10) and reduction (health book- in legal events let and sug- and motor vehi- gestion to cle accidents. contact physician if ques-

220 Alcohol Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness tions arise).

Measures: 48-month follow-up Kunz et al. 194 patients Intervention: Alcohol Use PP: Treatment (2004) presenting in Brief Counsel- Disorders a hospital ing session Identification ICER (per Alcohol emergency and health in- Test (AUDIT): one-point im- screening and department in formation I: 11.59 (SE provement in brief interven- the U.S. and packet. Aver- 8.99) AUDIT): tion in emer- screened for age cost C: 14.04 (SE $257.90 gency de- problem $632/patient. 9.17) partment drinking dur- ICER (per 1- ing visit. Pri- Control: d: .027 drink de- marily low- Health infor- crease in av- income Afri- mation packet Average erage number can-American only. Average Number of of weekly and Hispanic cost $497/ Weekly drinks): drinkers. 90 in patient (for Drinks: $218.70 intervention, screening). I: 17.19 (SE 104 in control. 26.47) ICER (per Measures: C: 20.08 (SE one-percent 3-month fol- 26.76) improvement low-up in heavy epi- d: .011 sodic drinking): Proportion $61.11 Heavy Drink- ing Episodes in Past Month: I: 58.89% C: 69.23%

Adults Seeking Treatment An Australian study focused on people seeking alcohol treatment after screening for risky alcohol use at a free, community-based counseling service. As the participants were actively seeking services, everyone was provided with treatment. Comparison to no intervention was not feasible. All participants were provided with personalized Normative Feedback comparing them to population norms as well as an informational pamphlet. Additionally, participants received one of two counseling treatments: Brief Intervention or Cognitive Behavioral Therapy (CBT). Brief Intervention, limited to one session, focused on FRAMES (feedback, responsibility, advice, menu, empathy, self-efficacy). While there were no significant differences in clinical effectiveness on any measure, the lower costs of im-

221 Alcohol Use plementing Brief Intervention made it more cost-effective than CBT on the available measures after six months (Shakeshaft et al., 2002).

Another study looked specifically at married persons with alcohol use disorder in outpatient counseling who were also actively seeking services to stop all alcohol use. All participants received individual alcohol counseling. In addition, some couples attended Behavioral Couples Therapy or a generic couples group with their spouse for ten weeks. After two years, all three options had a positive net benefit (i.e. the costs ascribed to the positive outcomes exceeded the costs of the intervention), but the additional costs of the Behavioral Couples Therapy meant it was not cost-effective. In other words, individual alcohol counseling was sufficiently cost-effective and combining it with Behavioral Couples Therapy did not provide additional cost benefits (O’Farrell et al. 1996; O’Farrell et al. 1992).

For persons with alcohol problems in the United Kingdom, both Motivational Enhancement Therapy (an established treatment option) and Social Behavior and Network Therapy (designed to utilize social networks to support behavior change) were considered cost-effective because they significantly reduced overall public sector costs (i.e. saved about five times as much as they cost); however, the therapies were not compared to usual care or no intervention. Between the two, Motivational Therapy was more clinically effective and marginally less cost- saving, with the relative cost-effectiveness depending on the willingness to pay threshold. If a QALY were not valued at anything, then Social Therapy had 74.7% likelihood of being more cost-effective, but at the standard willingness to pay threshold of £30,000 per QALY, Motivational Therapy had 58% likelihood of being the more cost-effective (UKATT Research Team, 2005a; UKATT Research Team, 2005b). In other words, Social Therapy was more cost-effective at lower willingness to pay thresholds, but as the threshold increased, the probability of Motivational Therapy being more cost-effective increased as well.

For persons with a diagnosis of Alcohol Dependence, different combinations of medication and behavioral interventions were compared to identify the most cost-effective option. The medications included naltrexone, acamprosate, naltrexone and acamprosate combined, or placebo. In each case, there was an option for the medication alone or in combination with a behavioral intervention (as well as the behavioral intervention alone). Notably, most of the options – including all medications with the behavioral intervention – were not cost-effective. However, the follow-up duration was only 16 weeks. Overall, placebo alone was the least expensive, and naltrexone and acamprosate combined was the most effective. Cost-effectiveness varied between placebo, naltrexone and acamprosate combined, and naltrexone alone depending on the willingness to pay threshold (Zarkin et al., 2008).

Lastly, a study in the Netherlands compared Internet-based interventions rooted in Cognitive Behavioral Therapy and Motivational Interviewing with or without therapist support. It found the Internet-based intervention with text-based chat therapy sessions more effective than the Internet-based self-help intervention alone. The Internet-based intervention with text-based chat was likely to be cost-

222 Alcohol Use effective at €14,710 per QALY or €3,683 per additional person who responded to treatment, with the QALY measure within standard willingness to pay thresholds (Blankers et al., 2012; Blankers et al., 2011).

Table 3. Behavioral Interventions for Alcohol Use for Adults Seeking Treatment Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Blankers et al. 136 adults Interventions: Percent PP: Societal (2012 & 2011) with harmful Based on Cog- Treatment Re- alcohol use in nitive Behav- sponders: ICER (per Internet-based a substance ioral Therapy I1: 53% QALY): interventions abuse treat- and Motiva- I2: 29% €201014,710 with and ment center tional Inter- (p=.06) without ther- website in the viewing. ICER (per apist support Netherlands. (1) Internet- Drinks in Last treatment re- for harmful 68 in interven- based therapy Week: sponder): alcohol use tion #1, 68 in including I1: 17.8 (19.9) €20103,683 intervention treatment ex- I2: 26.2 (25.0) #2. ercises plus (p=.03) Willingness to seven 40- pay threshold: minutes text- d: .374 If value is based chat €20K/QALY, therapy ses- Alcohol Use 60% probabil- sions. Aver- Disorders ity Internet- age cost €283/ Identification based self- participant. Test (AUDIT): help with chat (2) Internet- I: 12.6 (6.0) therapy ses- based therapy C: 15.0 (6.4) sions more of treatment (p=.02) cost-effective exercises than Internet- alone. Aver- d: .387 based self- age cost help alone. €12/participa nt.

Measures: 6 months Zarkin et al. 1,383 patients Interventions: Percent Days PP: Treatment (2008) with diagno- (1a) Medical Abstinent: sis of primary management I1a: 80.00% All ICER Combined Alcohol De- with naltrex- I1b: 75.90% measured dom- Pharma- pendence one for 16 I2a: 75.60% inated except cotherapies across 11 sites weeks. I2b: 78.30% for the follow- and Behavior- in U.S. 154 in (1b) 1a com- I3a: 80.50% ing: al Interven- intervention bined with I3b: 77.60% ICER (per 1- tion #1a, 155 in in- behavioral in- I4a: 73.80% percent im- (COMBINE) tervention tervention. I4b: 79.80% provement in for Alcohol #1b, 152 in (2a) Medical I5: 66.70% days absti-

223 Alcohol Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Dependence intervention management nent):

#2a, 151 in in- with Proportion of I1a: $200742.24 tervention acamprosate Patients Who I3a: $2007663.80 #2b, 148 in for 16 weeks. Avoid Heavy ICER (per pa- intervention (2b) 2a com- Drinking (SE): tient of avoid- #3a, 157 in in- bined with I1a: .35 (.04) ing heavy tervention behavioral in- I1b: .34 (.04) drinking): #3b, 153 in tervention. I2a: .33 (.04) I1a:

intervention (3a) Medical I2b: .35 (.04) $20072,846.85 #4a, 156 in in- management I3a: .39 (.04) I3a:

tervention with both nal- I3b: .28 (.04) $20078,095.12 #4b, 157 in trexone and I4a: .26 (.03) intervention acamprosate I4b: .31 (.04) ICER (per pa- #5. for 16 weeks. I5: .24 (.04) tient of (3b) 3a com- achieving bined with Proportion of good clinical behavioral in- Patients With outcome): tervention. Good Clinical I1a:

(4a) Medical Outcomes $20071,689.74 management (SE): I3a:

with placebo I1a: .74 (.04) $20077,543.18 for 16 weeks. I1b: .75 (.04) (4b) 4a com- I2a: .61 (.04) Willingness to bined with I2b: .75 (.04) pay threshold: behavioral in- I3a: .78 (.04) For percent tervention. I3b: .74 (.04) days absti- (5) Behavioral I4a: .58 (.04) nent, at values intervention I4b: .71 (.04) <$50, placebo only for 16 I5: .61 (.04) most likely to weeks. be more cost- effective, at Measures: $50-$350, nal- 16-week fol- trexone most low-up likely, at >$350, naltrexone and acamprosate most likely (up to 40%). UK Alcohol 608 clients Interventions: Number of PP: Public Treatment (age >16 (1) Social Be- Drinks Per Sector Trial (UKATT years) with havior and Drinking Day: Research alcohol prob- Network I1: 19.8 (SE ICER (per Team, 2005a lems across 7 Therapy to 1.15) QALY): & 2005b) sites in UK. help build so- I2: 18.7 (SE I2 vs. I1

261 in inter- cial networks 1.11) £200118,230

224 Alcohol Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Social Behav- vention, 347 to support d: .061 Willingness to ioral and in control. change in pay threshold: Network drinking be- Percentage of If no value per Therapy vs. haviors for Days Absti- QALY, 74.4% Motivational eight 50- nent: probability Enhancement minute ses- I1: 46.6% (SE Social Behav- Therapy for sions. Aver- 3.06) ior and Net- Alcohol Prob- age cost £221. I2: 45.4% (SE work Therapy lems (2) Motiva- 2.98) more cost- tional En- d: .023 effective than hancement Motivational Therapy com- Enhancement bining moti- Alcohol De- Therapy. At vational coun- pendence: standard val- seling and ob- I1: 11.2 (SE ue of £30K, jective feed- .766) 42.4% proba- back for three I2: 10.6 (SE bility more 50-minute .728) cost-effective. sessions. Av- d: .048 When value is erage cost £100K/QALY, £129. Alcohol- 33.8% proba- Related Prob- bility more Measures: lems: cost-effective. 12 months I1: 6.38 (SE .489) I2: 5.90 (SE .467) d: .060 Shakeshaft et 115 clients Interventions: Weekly Con- PP: Provider al. (2002) (age >16 (1) Brief Inter- sumption: years) in free, vention using I1: 24.9 (95% ICER: Brief Interven- community- FRAMES CI, 19.6 to I1: $2.80-2.95 tion vs. Cog- based drug (feedback, re- 30.1) I2: $6.69-8.10 nitive Behav- and alcohol sponsibility, I2: 25.0 (95% (p≤.01) ioral Therapy counseling advice, menu, CI, 20.0 to for clients in service in empathy, self- 29.9) Brief Interven- drug and al- Australia. efficacy) for tion is approx. cohol counsel- ~70% con- one session Binge Con- 2-3 times less ing sented; ~30% for max. 90 sumption: expensive than completed fol- minutes. Ap- I1: 15.4 (95% Cognitive Be- low-up. 61 in prox. $32.84/ CI, 11.9 to havioral Thera- intervention person. 18.9) py, with no #1, 54 in in- (2) Cognitive I2: 16.5 (95% significant dif- tervention #2. Behavioral CI, 14.1 to ference in effec- Therapy for 6 19.9) tiveness, mak- consecutive Alcohol Prob- ing it the more

225 Alcohol Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness 45-minute lems Ques- cost-effective weekly ses- tionnaire intervention. sions for max- (APQ): imum of 270 I1: 8.6 (95% minutes. Ap- CI, 7.5 to 9.8) prox. $76.53/ I2: 9.3 (95% person. CI, 8.1 to 10.5)

Measures: Alcohol Use 6-month fol- Disorders low-up Identification Test (AUDIT) ≥ 8: I1: 82.3 (95% CI, 75.2 to 88.1) I2: 82.4 (95% CI, 75.3 to 88.2)

No significant differences on any measure. O’Farrell et al. 34 couples Interventions: Husband’s PP: Societal (1996 & 1992) with newly Individual al- Marital Ad- abstinent male cohol counsel- justment Test Net Benefit:

Behavioral alcoholics in ing plus: (MAT): I1: $19925,824 Couples Ther- outpatient (1) Behavioral I1: 87.20 (9,286) apy for addic- counseling. 10 Couples Ther- (31.20) I2: -$19923,143 tion in interven- apy with anti- I2: 87.92 (10,342)

tion #1, 12 in abuse con- (31.20) C: $19927,131 intervention tract, home- C: 85.58 (5,106) #2, 12 in con- work assign- (42.26) trol. ments, behavioral rehears- Wife’s Marital Benefit-to- al, and com- Adjustment Cost Ratio: munication Test (MAT): I1: 8.64 (12.33) skills for 10 I1: 77.20 I2: -2.82 weeks. Cost (47.54) (12.32)

$1992857/partic I2: 75.50 C: 20.77 ipant. (30.99) (15.26) (2) Interac- C: 65.92 tional couples (41.45) Based solely on group with cost, adding mutual shar- Behavioral ing of feelings Couples Thera-

226 Alcohol Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness and problem Percent Days py to individual solving dis- Abstinent: alcohol therapy cussion for 10 I1: 79.07% was not cost- weeks. Cost (30.44) effective.

$1992895/ I2: 83.23% participant. (27.83) C: 66.41% Control: (39.98) Individual alcohol counseling alone.

Cost $1992d450/ participant.

Measures: 2-year follow- up

LIMITATIONS AND FUTURE DIRECTIONS One of the most fascinating aspects of excessive alcohol use is that it is both legal and common, including in non-recommended quantities and frequencies, even though the health and societal consequences are well known. In addition to clear linkages to liver disease, stroke, and cancer and to increased likelihood of accidents and injuries, excessive alcohol use has also been linked to larger societal issues such as domestic violence, marital conflict, and child abuse. While there are legislative attempts to address some of these negative outcomes (e.g., drunk driving laws) they have not been sufficient to stop excessive alcohol use in the United States.

The recommended treatment guidelines include screening adults in primary care settings to identify and target risky alcohol use, even amongst those who might not otherwise realize they have a problem or seek treatment. After screening, Brief Interventions are clinically effective and relatively low-cost (e.g., Normative Feedback, Brief Counseling); the greater costs appear to be the screening itself. Future investigations could test different screening processes; it is quite possible a brief or abridged screening tool could be more cost-effective. Related to this, despite the strong literature demonstrating the effectiveness of Brief Interven- tions, they have not been widely integrated into primary care practice. In addition to cost-effectiveness, it is important to understand other barriers to uptake.

Another major limitation of studies around alcohol treatment is that they typically require the consent of the participants, which implies a certain willingness to change. Thus, data from such studies may not be representative for individuals who would be disinterested in treatment or resistant to change. As with smoking, the health provider can make available relevant health information to inform

227 Alcohol Use patients’ choices, but cannot require individuals to participate in any intervention even if they receive a clinical diagnosis.

Given the wide-reaching social implications of excessive alcohol use, including effects on families and children, through accidents and from violent crime, most cost-effectiveness studies are not able to consider the full extent of costs that would be saved by decreased alcohol use. For instance, studies may be able to utilize legal records for car accidents, but they cannot easily measure the psychological impact on children living with an alcoholic parent who may, in turn, be more prone to violence and reckless behavior that impacts the household’s overall economic prospects. In short, the extent of alcohol’s effects are real and pervasive, and any cost benefits for reducing alcohol use into acceptable ranges is likely to be greater than estimated in the studies reviewed here.

KEY POINTS Adolescents and Young Adults • School-based family-focused preventive skills training programs for parents decreased lifetime prevalence for Alcohol Use Disorders with a net benefit for the families.

• For adolescents with prior excessive alcohol use, Motivational Interviewing to decrease alcohol use was a cost-effective strategy over usual care in boys based on gains in QALY.

• For college freshmen with prior excessive alcohol use, neither a session of Motivational Interviewing nor emailed Normative Feedback were cost- effective after three months. However, the combination of both had up to 75- 80% likelihood of cost-effectiveness.

Adults • For adults screened for risky alcohol use in the emergency room or primary care, both Brief Behavioral Counseling and Normative Feedback have the potential to be cost-effective for those with prior risky alcohol use. o After emergency room screening in Australia, mailing Normative Feed- back had the potential to be cost-effective for persons with alcohol-related incidents. o After emergency room screening in the United Kingdom, a referral to a health worker for Brief Counseling dominated an informational pamphlet alone for decreasing weekly alcohol consumption after a year. o After emergency room screening in the United States, a Brief Counseling session had the potential to be more cost-effective than an informational pamphlet for reducing weekly consumption or heavy drinking. o After primary care screening in the United States, Brief Counseling including Normative Feedback had a positive net benefit over an informational pamphlet after four years. o After sexual health clinic screening in the United Kingdom, a few minutes of Brief Advice with feedback on alcohol and health and an offer to make

228 Alcohol Use

a follow-up appointment was less cost-effective than a health information leaflet.

• For adults seeking treatment, shorter and individual therapies appear to be more cost-effective than longer or couple therapies. o For individuals seeking treatment after SBIRT, one session of Brief Coun- seling was similarly effective and less expensive than Cognitive Behavior- al Therapy after six months. o For married alcoholics in outpatient counseling, adding Behavioral Cou- ples Therapy was not more effective than adding a generic couples group or individual alcohol counseling alone. o For individuals with alcohol problems in the United Kingdom, both Moti- vational Enhancement Therapy and Social Behavior and Network Thera- py significantly reduced overall costs but were not compared to usual care or no intervention. • One study compared different medications to a behavioral intervention in combination or alone for Alcohol Dependence. Most options, including all with the behavioral intervention, were not cost-effective but the duration was limited to 16 weeks. For medication, cost-effectiveness depended on the willingness to pay threshold.

• One study compared Internet-based treatment with or without virtual therapist support in the Netherlands. The version with the therapist was more cost-effective per additional person who responded to treatment, within standard willingness to pay thresholds for QALYs.

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232 Tobacco Use

CHAPTER 9: TOBACCO USE

ABSTRACT Tobacco use is considered the largest component of preventable causes of death and disease in the United States. Using tobacco has severe health consequences including cancer, lung disease, and cardiovascular disease. Approximately 19% (43.8 million) of adults smoke cigarettes, of which 70% want to quit. Further- more, smoking is estimated to cost $193 billion annually, half in direct medical costs and half in lost productivity. Clinically effective pharmacotherapy and psychotherapy already exist, with the combination of both considered the most effective. Moreover, smoking cessation interventions are considered highly cost- effective, especially compared to other clinical disorders.

Counseling delivered in multiple formats (including via phone) and for varying intensities (including less than ten minutes) are all considered effective, with efficacy increasing in parallel with intensity. Although more intense behavioral interventions may be more costly, preliminary data suggest that the greater clinical improvements contribute to overall cost-effectiveness. In the studies reviewed here, a psychological intervention appeared more cost-effective than medication, although the difference was not significant. Combined behavioral and pharmacological treatment appeared cost-effective, with combinations including lower dosage medication being more cost-effective than those including higher dosage medication. However, the individual and combined treatments were not compared to each other. Internet-based computer-tailored programs were more cost- effective in video-based than text-based formats, and could be more cost- effective than a generic self-help program, generic text-based advice, or usual care. But, an internet-based computer-tailored program plus counseling was dominated by usual care. However, these were not compared to pharmacotherapy or psychotherapy.

For low-income pregnant women, psychotherapy was more cost-effective for smoking cessation during pregnancy but not post-pregnancy, while Motivational Interviewing was more cost-effective for relapse prevention (i.e. maintaining pri- or smoking cessation) post-pregnancy, but not for initiating smoking cessation during pregnancy. Despite the immense economic burden, cost-effective smoking cessation appears desirable and attainable.

BACKGROUND Tobacco is considered the most preventable cause of death and disease in the United States. While tobacco products including cigarettes are legal, their economic costs, addictive properties, and negative health consequences are well known. Health consequences include but are not limited to poor lung function, lung disease, cancer, cardiovascular disease, impotence, infertility, and death. Notably, smoking is considered the primary casual factor for at least 30% of mortality due to cancer and almost 80% of mortality due to chronic obstructive pulmonary disease, in addition to early cardiovascular disease and death (CDC, 2008). Smoking during pregnancy makes it harder to get pregnant; increases chances of miscarriage, premature birth, low birth weight, and birth defects; and is a risk factor for infant death (CDC, 2014). Importantly, quitting smoking at any

233 Tobacco Use age leads to positive health benefits; quitting before age 35 leads to mortality rates similar to having never smoked (CDC, 2011).

Additional health consequences for non-smokers can occur due to secondhand smoke. The U.S. Surgeon General concluded that any exposure to secondhand smoke increases health risk in both children and adults who do not smoke, leading to disease and premature death. In children, this includes increased risk for sudden infant death syndrome (SIDS), acute respiratory infections, ear problems, and more severe asthma. In adults, secondhand smoke has immediate adverse affects on the cardiovascular system and can cause cardiovascular heart disease and lung cancer (U.S. Department of Health and Human Services, 2006).

Tobacco Use Disorder Given the highly addictive properties of nicotine, a chemical in tobacco, most people who smoke find it difficult to quit and probably meet diagnostic criteria for Tobacco Use Disorder. Like other Substance-Related and Addictive Disorders (see Alcohol Use Disorder in Chapter 8), this diagnosis includes recurrent tobacco use that may exceed the person’s own intentions and persist despite the desire to decrease or quit use. Prior editions of the Diagnostic and Statistical Manual of Mental Disorders included Tobacco Dependence, which is defined by tolerance (e.g., same amount of tobacco has less effect or conversely require more tobacco to have same effect) and withdrawal (e.g., experience negative symptoms in the absence of tobacco or require tobacco to alleviate the symptoms). The updated manual (DSM-5), which combined the prior distinctions of Substance Abuse and Dependence into singular diagnoses, now also includes Tobacco Abuse (i.e. repeated use with negative consequences) as a criterion. In general, most people who use tobacco experience dependence, which means smoking cessation interventions are generally the same whether or not diagnostic criteria are assessed.

PREVALENCE OF SMOKING It is estimated that around 19% of adults in the United States currently smoke cigarettes, totaling 43.8 million adults in 2011. There is higher prevalence amongst males (21.6%) than females (16.5%), with more than three-quarters of smokers smoking daily (CDC, 2012a). For pregnant women, it is estimated that 10% smoked during the last three months of pregnancy (CDC, 2014); moreover, smoking during pregnancy is highest in women who are poor, single, and less educated (Dornelas et al., 2006).

For adolescents, the prevalence of smoking is 4.3% in middle school students and 15.8% in high school students (CDC, 2012b). Notably, the prevalence rate has decreased significantly among young adults (age 18 to 24 years), shifting from being the age group with the highest prevalence to the one with the second lowest after older adults (age more than 65 years; CDC, 2012a; CDC, 2012b). This is of particular importance given that almost 90% of smokers are believed to start smoking before the age of 18. Most significantly, almost 70% of current smokers said they wanted to quit in 2010 (CDC, 2011), which emphasizes the immediate demand for cost-effective interventions.

234 Tobacco Use

ECONOMIC BURDEN OF SMOKING Smoking is an expensive habit. For instance, a pack a day (20 cigarettes) is estimated to cost a smoker almost $2,000 per year or over $70,000 over 20 years. This online calculator helps calculate how much a given person spends on cigarettes, including annual prices increases: http://smokefree.gov/savings-future

Smoking exerts a significant societal toll with the annual economic burden estimated at $96 billion in direct medical costs and $97 billion in lost productivity costs, for a total of $193 billion in 2004 (CDC, 2008). For pregnant smokers, the direct medical costs due to low birth weight were estimated at an additional $511 per pregnant smoker or $263 million annually in 1995 (Lightwood et al., 1999). Meanwhile, the costs of parental secondhand smoke on children’s health were estimated around $4.6 billion in direct medical costs and $8.2 billion in premature mortality in 1993 (Aligne & Stoddard, 1997). In terms of lost productivity, a meta-analysis of occupational studies found smokers had a 33% higher risk of absenteeism and ex-smokers had a 14% higher risk; on average, current smokers were absent 2.74 more days per year than non-smokers (Weng et al., 2013). In terms of premature mortality, smoking was linked to almost 440,000 deaths annually, primarily due to health conditions like cancer, heart disease, and lung disease. For smoking during pregnancy, annual deaths were almost 800 infants. and secondhand smoke was responsible for the deaths of almost 50,000 non- smokers (CDC, 2008).

In addition to the long-term cost-savings of smoking cessation, there may be significant immediate cost benefits. Studies from the 1990s suggested that if smoking decreased by 1% per year, costs saved from acute myocardial infarction and strokes would be $3.2 billion over seven years (Lightwood et al., 1997). If smoking decreased by 1% per year among pregnant smokers, costs saved from low birth weight would be $572 million over seven years (Lightwood et al., 1999). Fi- nally, as counterpoint, some researchers have pointed out that while smoking cessation can lead to some decreased healthcare costs, it can also lead to other increased healthcare costs due to increased longevity (Barendregt et al., 1997).

CLINICALLY EFFECTIVE INTERVENTIONS Both pharmacotherapy and psychotherapy are effective for treating tobacco dependence, but they are most effective in combination. Thus, when possible, both medication and behavioral interventions are recommended.

Pharmacotherapy is recommended in all cases except for special populations like adolescents, pregnant women, or those with certain medical conditions. Im- portantly, light smokers may also be treated differently (e.g., no medication to start or lower dosages). Approved medications include sustained-release bupropion, varenicline, and nicotine replacement therapies (e.g., gum, inhaler, na- sal spray, patch). One study reviewed here also included nortriptyline, but current guidelines only recommend it for second-line treatment.

Behavioral interventions, namely counseling, are recommended in multiple delivery formats including individual or group settings or via the telephone. They are especially recommended for adolescents. Two key aspects of counseling for

235 Tobacco Use smoking cessation are Problem-Solving and Skills Training and Social Support. Brief Treatments of less than ten minutes, in which health professionals inquire about tobacco use and provide resources and assistance for quitting, can be effective, although not as effective as more intensive treatments. Overall, efficacy increases with intensity (e.g., duration and/or frequency of sessions). Cost- effectiveness studies can be useful to assess the benefit of the increased intensity relative to the increased costs.

By their very nature, most studies of smoking cessation only include persons who want to quit. In cases where the person may be uninterested in quitting, Motivational Interviewing, a technique where a therapist uses a non-judgmental stance to provide feedback on current use patterns and a menu of options to support change, is recommended. No clear recommendations have emerged specifically for relapse prevention (i.e. interventions to prevent a former smoker from starting to smoke again), although it is well known that it usually takes multiple quit attempts with relapses before a person successfully stops smoking.

Finally, interventions that promote physical activity alone or alongside other smoking cessation programs have demonstrated benefits in a few studies but lack sufficient data to draw conclusions at this time (Ussher et al., 2014).

COST-EFFECTIVENESS OF INTERVENTIONS Treatments for tobacco dependence—often including a combination of medication and behavioral interventions—are known to be highly cost-effective, especially compared to treatments for other clinical disorders (Clinical Practice Guideline, 2008). Additionally, telehealth smoking cessation interventions (e.g., via email, text messaging) appear to have small clinical improvements over generic self-help materials and are most likely to be cost-effective combined with in-person behavioral support (Chen et al., 2012).

Finally, it is worth noting that smoking cessation interventions also have the potential to be cost-effective for populations with co-occurring medical disorders, although no cost-effectiveness studies were identified to include in this chapter. For example, a meta-analysis of smoking cessation interventions in patients with chronic obstructive pulmonary disorder suggested both minimal and intensive counseling could be cost-effective (€16,900 and €8,200 per QALY, respectively), although pharmacotherapy dominated both of those options (€2,400 per QALY; Hoogendoorn et al., 2010). Clearly, more data on comorbidity are needed.

Psychotherapy and Pharmacotherapy Some cost-effectiveness studies focus on combined pharmacotherapy and psychotherapy for smokers in the general population. However, one study compared non-combined pharmacotherapy and psychotherapy to each other. Both medication (sustained-release bupropion or dosage-titrated nortriptyline) and a psychological intervention of group therapy (with placebo) had the potential to be more cost-effective than placebo alone depending on the willingness to pay threshold per person who stops smoking after a year, with cost-effectiveness appearing to favor the psychological intervention ($440 versus $1,509 or $741) alt-

236 Tobacco Use hough the difference was not significant (Hall et al., 2005; Hall et al., 2002). No comparison was made to a combined medication and psychological intervention.

Comparing minimally intensive and moderately intensive behavioral interventions combined with two different dosages of medication (sustained-release bupropion) found all four combinations were cost-effective per QALY after one year. While there were no statistically significant differences, combinations with lower medication dosage appeared to be more cost-effective than combinations with higher dosage. In other words, the higher medication dosage cost more with no additional clinical benefits (Javitz et al., 2004). Notably, no comparison was made to either behavioral intervention or medication dosage alone.

Similarly, comparing low, moderate, and high intensity behavioral interventions combined with nicotine replacement therapy looked at clinical effects and treatment costs but did not calculate overall cost-effectiveness. Both the high intensity and low intensity interventions were equally effective after a year. It is unclear, however, why the moderate intensity intervention was significantly less effective. Given the high intensity intervention cost more than the low intensity one, the low intensity intervention had the potential to be the more cost-effective option. In cases where there are no cost concerns or for specific populations, the high intensity option could also be recommended (Alterman et al., 2001). Nota- bly, no comparison was made to the behavioral interventions without nicotine replacement therapy or for nicotine replacement therapy alone.

Table 1. In-Person Behavioral Interventions for Smoking Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Hall et al. 120 cigarette Interventions: Percent Ab- PP: (2005 & 2002) smokers (10+ All include medi- stinence from Healthcare cigarettes/ cation manage- Smoking: Psychological day) who ment. I1: 29% ICER (per intervention wanted to (1) Sustained- I2: 23% person who vs. medica- quit smoking release bu- I3: 21% ceased smok- tion for smok- in U.S. 31 in propion for 12 C: 13% ing): ing cessation intervention weeks. Cost I1: $1,509 #1, 30 in in- $277/treatment. I2: $741 tervention #2, (2) Dosage- I3: $440 28 in inter- titrated nortrip- vention #3, 31 tyline for 12 in control. weeks. Cost $117/ treatment. (3) Placebo plus psychological intervention of 5 group therapy sessions for 12 weeks. Cost

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness $75/ treatment.

Control: Placebo for 12 weeks. Cost $40/ treatment.

Measures: 52 weeks Javitz et al. 1,524 smokers Interventions: 12-Month PP: Societal (2004) (average 23.2 All include sus- Non- cigarettes/ tained-release Smoking All ICER com- Different in- day) who bupropion (dos- Rates: pared to I1a. tensity behav- wanted to age listed). I1a: 23.6% ioral treat- quit smoking (1a) Minimal I1b: 25.7% ICER (per ments com- in U.S. 381 in intensity behav- I2a: 31.4% QALY): bined with intervention ioral interven- I2b: 33.2% I1b: $20022,877 different med- #1a, 378 in tion with tai- (NS) I2a: $2002699 ication dosag- intervention lored mailings I2b: $2002s1,173 es for smok- #1b, 382 in and dosage 150 ing cessation intervention mg for up to 8 ICER (per ad- #2a, 383 in weeks. Cost ditional non- intervention $119/person. smoker):

#2b. (1b) Same as 1a I1b: $20024,190 with dosage 300 I2a: $2002974 mg. Cost $207/ I2b: $20021,708 person. (2a) Moderate ICER (per life- intensity behav- time quitter):

ioral interven- I1b: $20026,652 tion with proac- I2a: $20021,547 tive phone calls I2b: $20022,712 from tobacco cessation specialist in first 6 months and dosage 150 mg for up to 8 weeks. Cost $195/person. (2b) Same as 2a with dosage 300 mg. Cost $283/ person.

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Measures: 1-year follow- up Alterman et 234 one-pack- Interventions: Percent Ab- PP: Interven- al. (2001) a-day smok- All include nico- stinence from tion ers with at tine replacement Smoking: Different in- least one pri- therapy for 8 I1: 27.0% Total Treat- tensity behav- or quitting weeks. I2: 12.0% ment Costs ioral treat- attempt. 75 in (1) Low- I3: 34.7% (per client): ments com- intervention intensity treat- I1: $308 bined with #1, 75 in in- ment with one No significant I2: $338 nicotine re- tervention #2, 30-minute edu- difference be- I3: $582 placement 75 in inter- cation session tween low- therapy for vention #3. with NP. intensity and High-intensity smoking ces- (2) Moderate- high-intensity treatment costs sation intensity treat- treatments. significantly ment with one more than low- 30-minute and intensity one. three 15-20- minute educational sessions with NP. (3) High- intensity treatment with four educational sessions with NP plus 12 weekly 45-50- minute sessions of Cognitive Behavioral Therapy.

Measures: 52 weeks

Internet-Based Computer-Tailored Programs A few studies assessed Internet-based computer-tailored smoking cessation programs, which in general cost less than intensive in-person services, and therefore may be cost-effective alternatives or additions for smoking cessation.

An Internet-based, computer-tailored smoking cessation program with counseling by practice nurses in the Netherlands had mixed findings after a year depending on the measure used. The program was dominated both by the computer-tailored program without counseling and by usual care in terms of cost per

239 Tobacco Use additional abstinent person. However, it cost €40,300 per QALY over usual care and €18,367 per QALY over the computer-tailored program without counseling; the latter is within standard willingness to pay thresholds. Meanwhile, the computer-tailored intervention without counseling could be more cost-effective than usual care at €5,100 per additional abstinent person, depending on the willingness to pay threshold for this metric (Smit et al., 2013). In sum, the computer- tailored program with counseling may be more cost-effective than the program without counseling, which in turn may be more cost-effective than usual care, depending on which clinical outcome is utilized by the decision-maker.

A similar Internet-based, computer-tailored smoking cessation program in the United Kingdom produced a modest increase in quit attempts but no difference in prolonged abstinence over a generic self-help program for smokers recruited in primary care. Overall, the Internet-based computer-tailored program cost £14,432 per QALY after six months and had a 54% to 58% likelihood of being more cost-effective than the generic self-help program within standard willingness to pay thresholds of £20,000 to £30,000. However, the researchers urged caution given the high levels of uncertainty around the estimates (Wu et al., 2014).

Finally, video- and text-based, computer-tailored smoking cessation programs in the Netherlands were compared to each other and to general text-based advice. The researchers noted that with the increasing use of videos and pictures in web- based technologies, text-based messages may not be as attractive to users as they have been previously. Overall, the video-based program led to more quitters and lower societal costs after a year, dominating the text-based program. Additional- ly, the video-based program was more effective and more expensive than generic text-based advice, which cost €60,000 per QALY but only €1,500 per additional percentage prolonged abstinence. While the former (in QALYs) was outside typical willingness to pay thresholds and indicated generic text-based advice was the most cost-effective option, the latter outcome (in prolonging abstinence) suggested the video-based intervention was the most cost-effective across all willingness to pay thresholds (Stanczyk et al., 2014). As discussed in the final section, quality of life might not be the best metric for smoking cessation, at least in the short- term, when individuals may still be experiencing negative withdrawal effects without realizing the longer-term health benefits.

Table 2. Internet-Based Computer-Tailored Behavioral Interventions for Smoking Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Stanczyk et 2,099 smokers Interventions: Percentage PP: Societal al. (2014) in the Nether- Internet-based Prolonged lands. 670 in computer- Abstinence: ICER (per Video- and intervention tailored smok- I1: 9.9% QALY): text-based #1, 708 in in- ing cessation, I2: 7.3% I1: €201360,000 computer- tervention #2, which incorpo- C: 6.4% I2: Dominated tailored in- 721 in control. rates readiness (p=.047) I1 vs. I2: terventions 99.2% with to quit (e.g., one Dominated for smoking cost data. route helps Percent 7-

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness cessation smokers trans- Day Point ICER (per ad- late intent into Prevalence ditional 1% action and in- Abstinence: prolonged ab- crease self- I1: 17.8% stinence):

efficacy and the I2: 17.7% I1: €20131,500 other focuses on I3: 16.2% I2: €201350,400 quitting smok- (NS) I1 vs. I2: ing): Dominated (1) Video-based intervention. Willingness to (2) Text-based pay thresh- intervention. old: At no value Control: per QALY, General text- 45% probabil- based advice. ity control and 38% Measures: probability 12-month fol- video-based low-up intervention more cost- effective. At value of €18K, 43% probability control and 39% probability video- based intervention. At no value per additional 1% prolonged abstinence, 42% probability both video- based intervention and control more cost-effective. At value of €18K, 70% probability video-based intervention.

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Wu et al. 3,309 smokers Intervention: Percentage PP: (2014) in UK. 1,514 Computer- Quit At- Healthcare in interven- tailored self- tempts: and Social Effectiveness tion, 1,795 in help interven- I: 32.3% Services of computer- control. tion with base- C: 29.6% tailored line advice re- ICER (per smoking ces- port and 4- Percentage 3- QALY): sation advice week progress Month Pro- £200914,432 in primary report. Estimat- longed Ab- care ed costs stinence: Willingness to (ESCAPE) £45/participant. I: 3.2% pay thresh- C: 2.7% old: Control: At values of Generic self- £20K-£30K/ help interven- QALY, 54%- tion with in- 58% probabil- formational ity the com- booklet. Esti- puter-tailored mated costs self-help in- £37/participant. tervention is more cost- Measures: effective than 6-month follow- the generic up self-help intervention. Smit et al. 414 smokers Interventions: Fagerström PP: Societal (2013) who wanted (1) Internet- Test for Nico- to quit smok- based comput- tine Depend- ICER (per Internet- ing in the er-tailored ence (FTND): QALY): based com- Netherlands. smoking cessa- I1: 4.76 (2.41) I1 vs. C puter tailor- 163 in inter- tion program I2: 5.21 (2.30) €40,300 ing with or vention #1, plus tailored C: 4.81 (2.46) without 132 in inter- counseling by Lower is better. I1 vs. I2 counseling vention #2, practice nurses. €18,367 for smoking 119 in control. Average cost d1: .021 cessation €57.70/group. d2: .168 I2 vs. C (2) Internet- d3 (I1 vs. I2): Dominated based comput- .191 ICER (per ad- er-tailored pro- ditional absti- gram only. Av- Percent Pro- nent person): erage cost longed Ab- I1 vs. C €7.70/group. stinence: Dominated I1: 8.6% Control: I2: 15.2% I1 vs. I2 Usual care. C: 10.1% Dominated

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Measures: I2 vs. C 12-month fol- €5,100 low-up

Smoking Cessation in Pregnant Women Given the negative health consequences for infants of mothers who smoke during pregnancy, some interventions specifically target pregnant women. Ideally, smoking cessation continues after pregnancy since secondhand smoke negatively affects children as well.

At a prenatal clinic, a psychotherapy session and scheduled monthly to bimonthly telephone follow-up by the therapist led to significantly higher abstinence rates during pregnancy and only cost $299 more per person who abstained from smoking compared to usual care by the end of pregnancy (Dornelas et al., 2006). This was considered cost-effective given the medical costs typically associated with complicated births (e.g., preterm births, low birth weight, neonatal intensive care); however, the clinical effects did not persist six months after pregnancy. Meanwhile, Motivational Interviewing delivered during home visits by nurses had differing results for smoking cessation and relapse prevention. For smoking cessation during pregnancy, Motivational Interviewing was dominated by usual care with no clinical differences and higher costs. However, for relapse prevention after pregnancy, the Motivational Interviewing was cost-saving at $628 saved per QALY at six months after pregnancy although it did cost $1,217 per relapse prevented. In other words, the Motivational Interviewing intervention was cost-effective in maintaining smoking cessation but not for initiating it (Ruger et al., 2008).

Table 3. Behavioral Interventions for Smoking in Pregnant Women Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Ruger et al. 302 low- Intervention: Proportion PP: Societal (2008) income preg- Motivational Smoking Ces- nant women Interviewing sation: ICER (per Motivational who are cur- for smoking I: 6% QALY): Interviewing rent smokers cessation and C: 8% Smoking Cessa- for lowin U.S. 156 in relapse pre- tion income preg- intervention, vention by Proportion Dominated nant smokers 146 in control. public health Relapse Pre- nurse. Aver- vention: Relapse Preven- age three 1- I: 43% tion

hour home C: 18% $1997628 saved visits plus (p=.055) self-help manual. Av- Infant Health ICER (per Life erage cost Outcomes: Year):

$1997309/ Birth Weight Smoking Cessa-

243 Tobacco Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness participant. (g) tion: I: 3241.2 (586) Dominated Control: C: 3321.3 Usual care (612.1) Relapse Preven- with an up-to- tion:

5-minute in- Low Birth $1997851 saved tervention Weight about harmful (<2500 g) ICER (per re- effects of I: 16 (59.3) lapse prevent- smoking dur- C: 11 (40.7) ed): ing/after $1,217 pregnancy NICU/Special plus self-help Care Unit manual. Av- I: 14 (10.1) erage cost C: 23 (17.6)

$19974.85/ participant. Respiratory Problems at Measures: Birth 6-months I: 21 (15.1) postpartum C: 23 (17.8) Dornelas et al. 105 low- Intervention: Percent Ab- PP: Interven- (2006) income preg- Prenatal clin- stinence at tion nant women ic-based 90- Pregnancy Prenatal clin- who are cur- minute psy- End: ICER (per ic-based rent smokers. chotherapy I: 28.3% non-smoker at counseling 66% Hispanic. session plus C: 9.6% end of preg- intervention 53 in interven- phone follow- (p=.015) nancy): for pregnant tion, 52 in up bi-monthly $2000298.76 smokers control. during preg- Percent Ab- nancy and stinence at 6 monthly after Months Post- delivery. 68% Partum: attendance. I: 9.4% Cost $56/ C: 3.8% patient. (p=.251)

Control: Usual care.

Measures: 6-months postpartum

244 Tobacco Use

LIMITATIONS AND FUTURE DIRECTIONS There are already promising data for the cost-effectiveness of existing pharmacological and psychological interventions to promote smoking cessation. Most cost- effectiveness studies focus on participants who want to quit or high-risk populations such as pregnant women; this is an optimal place to begin but future studies can also consider cost-effectiveness for those who may be initially resistant or opposed to smoking cessation. Promisingly, a behavioral intervention for those not ready to quit has undergone a pilot study and should be followed by a cost- effectiveness trial in the future (Taylor et al., 2014).

Many studies tested interventions including behavioral interventions combined with medication; combined behavioral and pharmacological treatment is considered the most effective clinical option. In terms of cost-effectiveness, the additional costs of two interventions may or may not be compensated for by the clinical benefits. As has been demonstrated thus far, combinations of different levels of intensity of behavioral interventions and different dosages of medication will provide insights on the optimal balance of economics and efficacy. However, these studies would benefit from including comparisons to each type of intervention alone as well. One study already suggested a behavioral intervention alone could be more cost-effective than medication alone, although in that case the findings were not significant and no comparison was made to a combined intervention. Similarly, studies of Internet-based, computer-tailored smoking cessation programs have demonstrated promising cost-effectiveness findings compared to a generic self-help program, generic text-based advice, and usual care, but have not been compared directly to psychotherapy, pharmacotherapy, or the combination of them both. Until then, we cannot conclude their overall cost- effectiveness.

Studying pregnant women is of vital importance not only from an economics perspective but also from a health perspective, as smoking during and after pregnancy leads to a litany of well-known immediate and lifelong health issues for the child. The studies included here focused on low-income women, but what ends up being cost-effective may be different for different socioeconomic populations. Notably, interventions that can lead to smoking cessation both during and after pregnancy are important, given the negative consequences of not only smoking for fetal development but also of secondhand smoke on child health. Similarly, smoking is strongly linked with several serious medical conditions. Behavioral interventions may not only benefit from targeting smoking within populations with these medical co-morbidities but might also improve cost- effectiveness by focusing on multiple health outcomes simultaneously.

A notable concern is relapse prevention. Smoking cessation often requires multiple quit attempts. Moreover, the process of smoking cessation can also include periods of relapse in which someone who has quit smoking once again begins to smoke. Currently, no recommended treatments exist specifically for relapse prevention; however, cost-effectiveness studies over longer durations will provide insights into the cost-savings of interventions that keep persons abstinent the longest. Interestingly, quality of life may not be the best measure of cost- effectiveness, at least in the short-term, as smoking cessation does lead to some

245 Tobacco Use negative effects in the beginning (e.g., withdrawal, weight gain) that might prevent the person from appreciating some of the longer-term benefits (e.g., decreasing risk of certain chronic conditions). Moreover, the smoker is not the only person who may experience quality of life improvements from smoking cessation, as secondhand smoke also impacts health. In these cases, measures of abstinence may be more informative.

Understandably, studies of cost-effectiveness include costs during the duration of the study, but it is difficult to factor in costs across the lifetime such as the costs saved for decreasing likelihood of health conditions like lung disease and cancer in smokers, or like low birth weight and infant death in the newborns of pregnant smokers. Finding a way to better account for these factors will likely increase the cost-effectiveness of any intervention considered.

KEY POINTS

Psychotherapy and Pharmacotherapy • Given the high direct medical costs of smoking, almost all treatments tested that lead to significant clinical improvements are considered cost-effective by some; however, additional data are needed to identify the optimal intensity of behavioral interventions and/or the ideal medication dosage to maximize economic efficiency as well as ascertain whether it is more cost-effective to provide them in combination, or alone.

• A psychological intervention had the potential to be more cost-effective than placebo after a year, at $440 per person who stops smoking. This was lower than the costs per person for two different types of medication, although the differences were not significant.

• All combinations of behavioral intervention (minimal or moderate intensity) and medication (lower or higher dosage) were considered cost-effective in terms of QALYs after a year, but the lower dosage combinations had the potential to be more cost-effective than the higher dosage combinations.

• Combined with nicotine replacement therapy, low and high intensity behavioral interventions were equally clinically effective to each other and more effective than a moderate intensity intervention after a year; however, the high intensity intervention cost more, suggesting the low intensity intervention may be the more cost-effective option.

Internet-Based Computer-Tailored Programs • Internet-based computer-tailored smoking cessation programs typically cost less than in-person services, and could be cost-effective options alone or as adjunctive treatment. However, they have not been directly compared to psychotherapy and pharmacotherapy. In general, they appear to be more cost- effective than a generic self-help program, generic text-based advice, or usual care.

246 Tobacco Use

• An internet-based computer-tailored program plus counseling by practice nurses was dominated by the computer-tailored program without counseling and by usual care on most measures. However, the program plus counseling increased QALY compared to the program without counseling at a cost within standard willingness to pay thresholds. The computer-tailored program without counseling may be more cost-effective than usual care for generating prolonged abstinence, depending on the willingness to pay threshold for this outcome.

• An internet-based computer-tailored smoking cessation program was potentially more cost-effective than a generic self-help program per QALY after six months.

• A video-based version of an Internet-based computer-tailored smoking cessation program was more cost-effective than both a text-based version and generic text-based advice in terms of prolonged abstinence, but generic text- based advice was more cost-effective option in terms of QALYs after a year.

Smoking Cessation in Low-Income Pregnant Women • In these two studies, a single-session of psychotherapy in clinic was cost- effective at initiating but not maintaining smoking cessation. Motivational In- terviewing during home visits was cost-saving at maintaining, but not initiating, smoking cessation for low-income pregnant women.

• One psychotherapy session at an antenatal clinic plus planned monthly to bimonthly telephone follow-up by the therapist significantly improved smoking cessation and was considered more cost-effective than usual care for generating abstinence during pregnancy. However, the clinical effects were not maintained at six months postpartum.

• Motivational Interviewing for smoking cessation provided by nurses during home visits was dominated by usual care at the end of pregnancy, but it was cost-saving at 6 months postpartum, suggesting its value for relapse prevention.

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Barendregt JJ, Bonneux L, van der Maas PJ. The health care costs of smoking. N Engl J Med. 1997 Oct 9;337(15):1052-7.

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249 Illicit Drug Use

CHAPTER 10: ILLICIT DRUG USE

ABSTRACT Illicit drug use includes use of illegal substances like heroin, cocaine, and methamphetamine and misuse of prescribed or non-prescribed pharmaceutical drugs like painkillers or sedatives. In all cases, illicit drugs have addictive, rewarding properties that can lead to dependence and abuse. When illicit drug use or medication misuse persists despite negative consequences, this behavior can be classified as a Drug Use Disorder. In the United States, illicit drug use has increased over the last several years, mostly due to the increased use of marijuana. As of 2013, 2.6% of Americans over age 12 had a Drug Use Disorder. Among persons with a Drug Use Disorder, more than 60% had a co-occurring Mood Disorder and more than 40% had an Anxiety Disorder. Illicit drug use is estimated to cost $193 billion annually, with more than $120 billion due to lost productivity (including incarceration and drug-related homicides). More than half of illicit drug users start before the age of 18, and more than half start with marijuana.

Cost-effectiveness studies for children and adolescents only compared interventions with each other and not to standard care or no care. For marijuana treatment, Adolescent Community Reinforcement Approach was more cost-effective than (1) combinations of Motivational Enhancement Treatment (MET) and group Cognitive Behavioral Therapy (CBT) with or without Family Network Support and (2) Multidimensional Family Therapy. For marijuana and/or alcohol treatment, treatment with MET plus CBT was more cost-effective when it did not include Assertive Continuing Care (ACC). The combination of MET and CBT was also more cost-effective than Chestnut's Bloomington Outpatient Program (CBOP) whether or not CBOP included ACC. For youth with illicit drug use who were referred to treatment, there were no clear clinical or cost differences between four different interventions: Skills-Focused Psychoeducation, individual CBT, Functional Family Therapy (FFT), or combined CBT and FFT.

Data for adults are limited to one study per illicit drug. For stimulant users, a prize-based Contingency Management program may be more cost-effective than standard care depending on the willingness to pay threshold for each additional week a person is abstinent (if value is $205, only 10% likely; if value is $325, then 90% likely). For benzodiazepine misuse, slowly reducing the dosage (i.e. tapering) dominated a combination of tapering plus group CBT and may be more cost-effective than usual care at $22 per additional percent abstinence, depending on the willingness to pay threshold. For opiate users already on methadone maintenance, a moderate level of supervised care (three times a week) was more cost-effective than minimal care (one time a week) and enhanced care (seven times a week).

Lastly, for continuing care after intensive residential or day substance use treatment programs, there were no clinical differences between standard aftercare and the addition of the more expensive Contracting, Prompting and Reinforcing aftercare, suggesting standard aftercare would be the more cost-effective option. Without standard willingness to pay thresholds for most of these measures, cost- effectiveness ultimately depends on the decisionmaker. Overall, more studies

250 Illicit Drug Use comparing the different types of interventions and targeting the different illicit drugs are imperative.

BACKGROUND Illicit drugs refer both to addictive and psychoactive illegal drugs, and to non- prescribed or misused pharmaceutical drugs. While it is legal in the United States for adults to use the addictive and psychoactive drugs alcohol and tobacco (see Chapters 8 and 9), it is illegal to use drugs such as heroin, cocaine, and methamphetamine; to use medications without a prescription; or to misuse prescription medications.

Commonly used illegal drugs include marijuana (cannabis), stimulants (e.g., cocaine, methamphetamine), opioids (e.g., heroin), hallucinogens (e.g., LSD), and MDMA (ecstasy). The Federal Drug Administration (FDA) has concluded that all of these substances have high risks and low benefits, classifying them as inappropriate for medicinal or recreational use. Commonly misused prescription medications include prescription painkillers (e.g., oxycodone, morphine, codeine, fentanyl), prescription sedatives (e.g., benzodiazepines, barbiturates), and prescription amphetamines (e.g., Ritalin, Adderall, Dexedrine). While the FDA has approved formulations of these drugs for safe and beneficial medicinal use, they can be harmful and addictive if taken in a different manner than prescribed (e.g., altering amount, frequency, or route) or without a prescription.

A consistent danger with illicit drugs is their addictive, rewarding properties that encourage development of compulsive and repetitive, punishment-resistant use patterns. Some illicit substances also have serious immediate risks that can occur with a single use; for example, overdose on opioids can cause death due to respiratory depression and marijuana can cause psychosis.

Drug Use Disorder Substance Use Disorder is the overarching term for conditions where repeated use of a substance results in development of compulsive use patterns despite negative consequences (e.g., inability to stop use, risky use in hazardous situations, social impairment). This includes conditions previously referred to as Sub- stance Abuse (e.g., repeated use despite negative consequences) and Substance Dependence (e.g., increased tolerance, withdrawal symptoms when use is stopped). Further classifications focus on the specific substance, although many of the diagnostic criteria are identical across the difference substances. Alcohol Use Disorder and Tobacco Use Disorder are included in prior chapters; in this chapter we focus on the broad class of Drug Use Disorders (e.g., Cannabis Use Disorder).

Diagnostic criteria focus less on the legality of the substance use (e.g., that it is illegal or misused) and more on the adverse effects of the continued substance use on the person’s behavioral, physiological, emotional, and social functioning. Unsurprisingly, Drug Use Disorder often co-occurs with other neuropsychiatric disorders and much of the available data focuses on these comorbidities. For adults with a Drug Use Disorder, a large population survey estimated that 60%

251 Illicit Drug Use also had at least one independent (i.e. not substance induced) Mood Disorder, 43% had at least one independent Anxiety Disorder, and, 47.7% had at least one independent Personality Disorder (Grant et al., 2004a; Grant et al., 2004b). These rates are much higher than for Substance Use Disorders more generally.

State-Allowed Marijuana Use Although the FDA has approved the cannabinoid-based medications marinol and nabilone since 1985, marijuana (cannabis) use for medicinal purposes has not been approved. However, there are some states in which voters have declared marijuana to be medicinal. These states allow physicians to recommend marijuana to patients and allow entrepreneurs to sell marijuana to those with physician recommendations. Other states now allow entrepreneurs to sell marijuana for recreational use, despite scientific evidence of negative effects and risks over the short and long term. Regardless of these new legal statuses, clinical trials have yet to demonstrate beneficial effects of marijuana that outweigh the negative effects. For example, trials have shown that marijuana can reduce spasticity in patients with multiple sclerosis, but that it can also reduce cognitive function in these patients, having questionable benefits on quality of life (Honarmand et al., 2011; Corey-Bloom et al., 2012). Similarly, although marijuana has been shown to reduce pain, this pain relief is minimal and not considered clinically significant. Specifically, marijuana has been shown to reduce pain by about half a point on a 0-10 scale of pain severity (e.g. taking pain from a 7 to a 6.5), far less than the standard 30% reduction in pain that patients typically require to notice the difference. As this limited effect comes at the expense of addiction risk, cognitive and emotional impairment, and risk of bronchitis (Martín-Sánchez et al., 2009), the FDA still deems marijuana as inappropriate for medical use.

There is now extensive evidence of the addictive nature of marijuana use. Mari- juana acts directly on the brain’s reward circuitry to artificially amplify the brain’s expectations about the benefits of marijuana use. As use over time leads to addiction and dependence (i.e. where stopping use causes the user distress and unpleasant symptoms for weeks), many users maintain consistent daily use for years or even decades. Current estimates suggest that about 40% of the overall population that ever use marijuana experience these dependence and withdrawal effects (SAMHSA, 2012).

PREVALENCE OF ILLICIT DRUG USE Illicit drug use is common in the United States. The addictive properties of these substances can quickly cause individuals to use them recurrently. Illicit drug use rose from 8.3% of the population in 2002 to 9.2% in 2012. This increase was mostly driven by increased use of marijuana, as use of most other illicit drugs has remained about the same. In particular, marijuana use for persons age 12 years and older has increased from about 5.8% current users in 2007 to 7.3% in 2012. Over- all, marijuana is considered the most common illicit drug; more than half of first- time drug users start with marijuana (NIDA, 2015).

The 12-month prevalence of Substance Use Disorder (including alcohol but not including tobacco) was 8.2% or 21.6 million people as of 2013. Looking at specific substances, the prevalence of Alcohol Use Disorder was 6.6%, Drug Use Disorder

252 Illicit Drug Use was 2.6%, Cannabis Use Disorder was 1.6%, Opioid Use Disorder (other than heroin) was 1.9 %, Heroin Use Disorder was 0.2%, and Cocaine Use Disorder (including crack cocaine) was 0.9%. Smaller proportions of the population had Am- phetamine Use Disorder, Sedative Use Disorder, Hallucinogen Use Disorder and Tranquilizer Use Disorder (SAMHSA, 2014).

Importantly, young adults (age 18 to 25 years) are the age group with the highest number of current illicit drug users (21.2% as of 2009), and adolescents (age 12 to 17 years) also have elevated illicit drug usage (10% as of 2009; NDIC, 2014). More than half of first-time drug users were under the age of 18 in 2012 (NIDA, 2015).

ECONOMIC BURDEN OF ILLICIT DRUG USE Illicit drug use is estimated to cost the United States more than $193 billion annually in both direct and indirect public costs as of 2007, with only $11.4 billion due to healthcare costs, $61.4 billion due to crime, and $120.3 billion due to lost productivity. Within the lost productivity costs, more than $48 billion are due to incarceration costs and another $4 billion to drug-related homicides (NDIC, 2014). Additional data exist for costs due to some specific illicit drugs; for example, Heroin Use Disorder was estimated to cost $21.9 billion in direct and indirect cost as of 1996 (Mark et al., 2001). The data suggest that prevalence and costs are not directly correlated; some drugs incur a higher economic burden than others.

One aspect of early mortality unique to illicit drug use is overdose (i.e. the use of a substance in sufficient quantities that lead to death). While intentional overdose is one method to inflict deliberate self-harm (see Chapter 6), it can also occur ac- cidentally. However, data do not always distinguish between the two; current data indicate the number of deaths due to overdose of prescription medications exceeds the combined number of deaths due to overdoses on cocaine, heroin or methamphetamine (NDIC, 2014). Another aspect that contributes significantly to costs is the illegal status of substances, which consequentially involves law enforcement and criminal justice systems. The associated costs occur at multiple preliminary stages including illegal drug production, trafficking, and distribution as well as ultimate drug use.

CLINICALLY EFFECTIVE INTERVENTIONS There are numerous evidence-based, clinically effective interventions for the treatment of Drug Use Disorders. Most generally, there are a number of psychosocial treatments that have been shown to reduce substance use and/or increase abstinence rates in persons with Substance Use Disorders. These include Cogni- tive Behavioral Therapy, Motivational Enhancement Therapy, Twelve-Step Facil- itation, and treatments that include family or community members, such as Be- havioral Couples Therapy and Community Reinforcement Approach. Addition- ally, Contingency Management Programs, which provide rewards for abstinence or other recovery-oriented behaviors, are also clinically effective.

Generally, these treatments focus on modifying thoughts, emotions, and behavioral patterns by identifying triggers and response patterns that maintain drug use; learning effective ways to avoid triggers, cope with stress, and solve prob-

253 Illicit Drug Use lems; developing supportive social networks to encourage abstinence; and developing alternate rewarding activities. Treatment may include significant others, family members, and the community to reshape interactions and environments to reduce the drive to use drugs. Contingency Management Programs, which provide rewards for abstinence or other recovery-oriented behaviors, have also been shown to be effective.

In addition to psychosocial treatments, several medications have been shown to be effective for treatment of Opioid Use Disorders, including opioid agonist treatment with methadone or buprenorphine (i.e. binds consistently to the receptors to generate constant activation, thereby preventing the time-linked activation that drives behavioral choices), and opioid antagonist treatment with naltrexone (i.e. blocks the receptors so opioids cannot bind to them). Methadone treatment can only be delivered in specially licensed clinics. Buprenorphine can be provided by physicians in general clinical settings, once the physician obtains a prescribing waiver. There are no restrictions on prescribing naltrexone, but effectiveness of the oral formulation is limited by lack of adherence to the prescription. A depot version, which delivers medication over the course of a month, has been developed to overcome this limitation. No effective pharmacotherapies have been developed for other Drug Use Disorders.

COST-EFFECTIVENESS OF INTERVENTIONS A limited number of studies are available for illicit drug use in children and adolescents (primarily marijuana) and in adults (full spectrum of illicit substances).

Illicit Drug Use in Children and Adolescents Only three studies assessed cost-effective options for treating illicit drug use in children and adolescents. One focused specifically on Cannabis Use Disorder and the other two more broadly on Substance Use Disorders but these latter two still primarily included young people with Cannabis Use Disorder.

For Cannabis Use Disorder, two large-scale studies assessed five time- and resource-intensive interventions, some with similar components but varying in duration or frequency (Dennis et al., 2004). Two interventions combined individual Motivational Enhancement Treatment (MET) and group Cognitive Behavioral Therapy (CBT), one with additional CBT sessions. Another intervention further added Family Support Network with parent education sessions, therapeutic home visits, referral to self-help groups, and case management. Comparing these three options, the least intensive option (only MET and CBT, with the lesser number of CBT sessions) dominated as most cost-effective per person in recovery (i.e. living in the community with no substance use in the past month after 12 months). The fourth and fifth interventions (Adolescent Community Reinforce- ment Approach and Multidimensional Family Therapy) both combined individual, parent, and family components. Adolescent Community Reinforcement Ap- proach dominated the most cost-effective option of the original three (MET plus CBT, with fewer CBT sessions). MET plus CBT, with fewer CBT sessions, dominated the Multidimensional Family Therapy in terms of cost per person in recovery. In short, Adolescent Community Reinforcement Approach was the most cost-effective overall, with combined MET and CBT without Family Network

254 Illicit Drug Use

Support following second. None of the interventions were compared to standard care or no intervention.

For adolescents with Cannabis Use Disorder, Alcohol Use Disorder, or both, two treatments were compared: Chestnut’s Bloomington Outpatient Program (CBOP), which consists of multiple treatment components to increase the desire to change, provide necessary skills, and create an environment supportive for this change, and combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). Each treatment was provided either with or without As- sertive Continuing Care (ACC), home-based continuing care for 12 to 14 weeks. Based on the average cost per day abstinent and per person in recovery after 12 months, MET/CBT without ACC was the more cost-effective option than with ACC and than CBOP with or without ACC at $4.25 per day abstinent or $2,620 per person in recovery at 12 months. Again none were compared to standard care or no intervention (Godley et al., 2010).

Finally, for Substance Use Disorders more generally (where marijuana was most often the primary drug of abuse), four interventions were compared: Individual Cognitive Behavioral Therapy (CBT), Functional Family Therapy (FFT), integrative treatment combining CBT and FFT, and Skills-Focused Psychoeducation. While there were some differences in clinical effectiveness after four months, there were none after seven months for either frequency of marijuana use or juvenile delinquency outcomes. The researchers concluded Skills-Focused Psy- choeducation was the least expensive per median episode, suggesting it may be the most cost-effective; however, no cost differences were apparent within the annual or weekly costs per patient, so we argue there is not enough evidence to conclude any of the interventions are more cost-effective than the other. Moreo- ver, none were compared to standard care or no intervention (French et al., 2008).

Table 1. Behavioral Interventions for Illicit Drug Use in Children and Adolescents Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Dennis et al. 600 adoles- Interventions: Days of Ab- PP: Societal (2004) cents (age 12- (1) 2 individ- stinence: 18 years) with ual sessions of Trial 1 ICER (per day Collaborative Cannabis Use Motivational I1: 269 of abstinence) Youth Treat- Disorders and Enhancement I2: 256 Trial 1 ment for can- their families Therapy I3: 260 I1: $19994.91 nabis use in across 4 sites (MET) and 3 I2: $19996.15 youth in U.S. 83% group ses- Trial 2 I3: $199915.13 male. In Trial sions of CBT I1: 251 (I1 and I2 sig- 1, 102 in infor 5 sessions I4: 265 nificantly lower tervention #1, total over 6-7 I5: 257 than I3; p<.05) 96 in interven- weeks. tion #2, 102 in (2) Same as 1, Proportion in Trial 2

intervention plus 7 addi- Recovery at I1: $19999.00 #3. In Trial 2, tional CBT Study End: I4: $19996.62 100 in inter- sessions for 12 Trial 1 I5: $199910.38

255 Illicit Drug Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness vention #1, sessions total I1: 28% (I4 trending 100 in inter- over 12-14 I2: 17% lower than I1 vention #4, weeks. I3: 22% and I5) 100 in inter- (3) Same as 2, vention #5. plus Family Trial 2 ICER (per Support Net- I1: 23% person in re- work with 6 I4: 34% covery at parent educa- I5: 19% study end): tion group Trial 1

meetings to No significant I1: $19993,958 improve par- differences on I2: $19997,377 ent know- any outcomes. I3: $199915,116 ledge and (I1 significant- skills, 4 thera- ly less than I2; peutic home both I1 and I2 visits, referral significantly to self-help less than I3; support p<.05). groups, and case manage- Trial 2

ment to pro- I1: $19996,611 mote adoles- I4: $19994,460 cent/parent I5: $199911,775 treatment en- (I4 significant- gagement. ly less than I1; (4) Adolescent both I4 and I1 Community significantly Reinforce- less than I5). ment Ap- proach, with In Trial 1, Mo- 10 individual tivational En- sessions, 4 hancement sessions with Therapy (MET) caregivers (2 plus Cognitive with whole Behavioral family), and Therapy (CBT) limited case dominated add- management ing more CBT for 12-14 sessions or add- weeks. ing Family (5) Multidi- Support Net- mensional work. Family Ther- apy, with 6 In Trial 2, Ado- individual lescent Com- sessions, 3 munity Rein-

256 Illicit Drug Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness with parents, forcement Ap- 6 with whole proach domi- family, and nated both case manage- MET/CBT and ment for 12-15 Multidimen- sessions over sional Family 12-14 weeks. Therapy, and MET/CBT Measures: dominated 12-month fol- Multidimen- low-up sional Family Therapy. Godley et al. 320 adoles- Intervention: Percentage of PP: Treatment (2010) cents (age 12- Assertive Con- Days Absti- 18 years) with tinuing Care nent from Al- Average Cost Adolescent Substance Use (ACC) is home- cohol or Other (per episode): outpatient Disorders in based care for Drugs for Past I1a: treatment and U.S. 76% 12-14 weeks. 90 Days: $19975,303.14 continuing male. 73% in- (1a) Chest- I1a: 81.8% I1b: care for Sub- volved in ju- nut’s Bloom- I1b: 78.0% $19973,246.66 stance Use venile justice ington Outpa- I2a: 79.3% I2a:

Disorders system. 75% tient Program I2b: 85.0% $19973,655.95 Cannabis Use (CBOP) to in- I2b:

Disorder, 49% crease desire GAIN’s Sub- $19971,143.89 Alcohol Use to change, stance Prob- Disorder, 35% provide nec- lem Scale Average Cost both Cannabis essary skills, (SPS) for Past (per day ab- and Alcohol and create en- Month: stinent):

Use Disor- vironment I1a: 1.2 I1a: $199719.37 ders. 80 in in- supportive for I1b: 1.68 I1b: $199714.00 tervention this change. I2a: 1.2 I2a: $199714.97 #1a, 80 in in- With ACC. I2b: 1.2 I2b: $19974.25 tervention (1b) CBOP #1b, 81 in in- without ACC. No significant Average Cost tervention (2a) Motiva- differences in (per person in #2a, 79 in in- tional En- clinical out- recovery at 12 tervention hancement comes. months): #2b. Therapy and I1a:

Cognitive Be- $199713,945.28 havioral I1b:

Therapy $199711,131.42 (MET/CBT) I2a:

for 2 individ- $199712,113.57 ual sessions, 3 I2b:

group ses- $19972,619.87 sions, 2 family

257 Illicit Drug Use

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness sessions. With Based on cost ACC. per day absti- (2b) nent and per MET/CBT person in re- without ACC. covery at 12 months, Measures: MET/CBT 12-month fol- without ACC low-up was the most cost-effective condition. French et al. 114 adoles- Interventions: Percent Days PP: Treatment (2008) cents (age 13- (1) Individual of Marijuana 17 years) with Cognitive Be- Use: Total Annual Comparing illicit drug use havioral I1: 51.8% Costs: four interven- and their fam- Therapy (37.6) I1: $199812,830 tions for ado- ilies referred (CBT). I2: 39.8% I2: $199816,877 lescents with for substance (2) Functional (39.4) I3: $199824,643 illicit drug use abuse treat- Family Ther- I3: 35.4% I4: $19989,471 ment in U.S. apy (FFT). (26.6) Most youth (3) Integrative I4: 40.7% Annual Costs reported can- treatment (39.3) (per client):

nabis as pri- combining (NS) I1: $19985,554 mary drug of CBT and FFT. I2: $19987,061 abuse. 31 in (4) Skills- YSR Juvenile I3: $199811,544 intervention Focused Psy- Delinquency I4: $19986,150 #1, 30 in in- choeducation- Subscale tervention #2, al Group. (lower scores Average Cost 29 in interven- are better): (per treatment tion #3, 30 in Measures: I1: 10.4 (4.7) episode):

intervention 7-month fol- I2: 9.2 (3.8) I1: $19981,278 #4. low-up I3: 8.5 (4.2) I2: $19981,625 I4: 9.4 (3.7) I3: $19982,546 (NS) I4: $1998885

Illicit Drug Use in Adults One study each was available specifically for stimulants, benzodiazepines, and opiates, with a fourth focused on aftercare after intensive treatment for Substance Use Disorders (two-thirds with Drug Use Disorders).

For stimulant abusers (who may or may not also use alcohol), prize-based Con- tingency Management has the potential to be more cost-effective than usual care depending on the willingness to pay threshold. In this intervention, participants who tested negative for stimulant use received prizes, and their chances of winning prizes increased the longer they tested negative. If the value was $205 per additional week that the person was abstinent from stimulants, there was only a

258 Illicit Drug Use

10% likelihood the Contingency Management was more cost-effective than usual care after 12 weeks. However, if the value was $325 per additional week that the person was abstinent, then there was 90% likelihood the Contingency Manage- ment was more cost-effective (Olmstead et al., 2007).

For adults abusing benzodiazepines (a prescription sedative) for an average of 13.5 years, tapering (i.e. slowly reducing dosage) of benzodiazepine dose, and taper in combination with group Cognitive Behavioral Therapy (CBT) were both compared against usual care. After 18 months, tapering alone led to a greater abstinence (36%) than the more expensive combination of tapering plus group CBT (29%). In terms of cost-effectiveness, tapering alone dominated the combined tapering plus group CBT. Moreover, tapering alone cost approximately $22 per each additional percent abstinent, which could be cost-effective depending on the willingness to pay threshold for this metric (Oude Voshaar et al., 2006a; Oude Voshaar et al., 2006b).

For opiate abusers, a commonly accepted pharmaceutical intervention is methadone maintenance. Methadone interacts with the same receptor targets as the illicit opiate drug; the long-acting properties of methadone block the high and the rewarding effects of taking illicit opioids while preventing cravings and withdrawal symptoms that typically occur after quitting opiate use. For patients already receiving methadone maintenance, three levels of additional psychosocial services were compared: The first provided a minimal level of supervised care (1 session per month), the second provided the typical clinical standard of a moderate level of supervised care (3 sessions a week, including behavioral interventions), and the third provided an enhanced level of supervised care (7 sessions a week, including medical, psychiatric, employment, and family therapy services). After six months, the moderate level of supervised care appeared to be the most cost-effective option with lowest annual costs per abstinent client, followed by enhanced care then minimal care. The incremental cost per additional abstinent person was $2,289 for moderate care compared to minimal care, which again will depend on willingness to pay threshold for this metric (Kraft et al., 1997; McLel- lan et al., 1993).

Finally, a study of adults with Substance Use Disorder (33% alcohol dependence, 67% drug dependence with or without alcohol use) focused on continuing care in the 12 months following intensive residential or day treatment programs. Stand- ard practice for aftercare includes meeting with an addiction therapist during the final week of treatment and nine weeks afterward, as well as encouragement to participate in weekly aftercare groups and weekly Alcoholics Anonymous (AA) or Narcotics Anonymous (NA) meetings. A previously tested aftercare intervention, Contracting, Prompting and Reinforcing (CPR), included the standard care above plus a behavioral contract, reminders for all aftercare appointments, and other social reinforcement tools (i.e., certificates, honor roll, medallions). While the CPR intervention was more expensive at $98.25 per participant, there were no significant differences in clinical effectiveness. Given this, no formal cost- effectiveness analysis was conducted. It can be concluded that the standard aftercare program was the more cost-effective option (Lash et al., 2013).

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Table 2. Behavioral Intervention for Illicit Drug Use in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Olmstead et 415 stimulant- Intervention: Longest Dura- PP: Treatment al. (2007) abusing par- Usual care tion of Con- ticipants (e.g., plus prized- firmed Stimu- ICER (per ad- Motivational cocaine, am- based Contin- lant Absti- ditional LDA Incentives for phetamine, gency Man- nence in week): Enhanced methamphet- agement with Weeks (LDA): $258 (95% CI, Drug Abuse amine) who abstinence- I: 4.3 (4.6) 191-401) Recovery may also use based incen- C: 2.6 (3.4) (MIEDAR) or abuse alco- tives to rein- d: .425 Willingness to prize-based hol across 8 force behav- pay threshold: Contingency outpatient iors (e.g., with Number of If value is Management treatment chances to Negative $205/ addi- for stimulant clinics. 209 in win prizes for Urine Sam- tional LDA abusers intervention, negative test ples: week, then 206 in control. results) for 12 I: 12.6 (9.0) 10% probabil- weeks. Num- C: 9.6 (8.0) ity prize- ber of chances based Contin- at winning d: .353 gency Man- prizes in- agement pro- creases with Length of Stay gram more continuous in Study cost-effective abstinence. (Weeks): than usual I: 8.1 (4.2) care alone. If Control: C: 7.0 (4.4) value is $325, Usual care for then 90% 12 weeks. d: .256 probability more cost- Measures: effective. 12 weeks Oude Voshaar 180 patients Interventions: Percentage of PP: Societal et al. (2006a & who used (1) Group Patients Ab- 2006b) benzodiaze- Cognitive Be- stinent: ICER (per ad- pines (mean havioral I1: 29% ditional 1- Tapering off duration 13.5 Therapy plus I2: 36% percent dis- benzodiaze- years) in the benzodiaze- C: 15% continuation): pines in long- Netherlands. pine taper. I1: €200162.53 term users 70% female. Average cost I2: €200121.69 73 in interven- €172.99/patie I2 dominates tion #2, 73 in nt. I1 intervention (2) Benzodi- #2, 34 in con- azepine taper trol. alone. Aver- age cost €69.50/ patient.

260 Illicit Drug Use

Control: Usual care.

Measures: 18-month follow-up Kraft et al. 100 metha- Interventions: Percent Ab- PP: Treatment (1997) & done- All include stinent from McLellan et maintained methadone Opiates and Annual Cost al. (1993) opiate users. treatment. Cocaine: (per abstinent 88% male. 31 (1) Minimal I1: 30% client):

Counseling in interven- supervised I2: 55% I1: $199316,485 support ser- tion #1, 36 in care (1 coun- I3: 68% I2: $19939,804 vices during intervention seling session (p<.05) I3: $199311,818 methadone #2, 33 in in- per month) maintenance tervention #3. for 24 weeks. Improvement ICER (per ad- for opiate us- (2) Regular in Number of ditional absti- ers counseling Days of Use: nent client): sessions Opiate I2 vs. I1 (3x/week, in- I1: 3 $2,289 cluding be- I2: 3 havioral in- I3: 5 I3 vs. I2 terventions) (NS) $22,410 for 24 weeks. (3) Enhanced Cocaine Providing mod- counseling I1: 3 erate levels of (7x/week) I2: 1 support ser- with medical, I3: 3 vices is more psychiatric, (NS) cost-effective employment, than providing and family enhanced or therapy ser- minimal levels vices for 24 of service. weeks.

Measures: 6-month follow-up Lash et al. 183 graduates Continuing Percent At- PP: Treatment (2013) of two inten- care following tended 12 sive Substance treatment. Months of Incremental Contracting, Use Disorder Treatment: Cost (per par- Prompting, programs. Intervention: I: 16% ticipant): and Reinforc- 33% alcohol (1) Contract- C: 10% $98.25 ing aftercare dependent, ing, Prompt- intervention 67% drug de- ing and Rein- Days of Higher costs for Substance pendent (with forcing after- Monthly Al- but no differ- Use Disorder or without al- care interven- coholics/ ence in clinical

261 Illicit Drug Use

cohol use). tion for 12 Narcotics effectiveness, so 96% male. 92 months. In Anonymous no cost- in interven- addition to Attendance: effectiveness tion, 91 in standard I: 14.18 (23.21) analysis con- control. treatment, C: 12.41 ducted. complete be- (21.57) havioral contract, receive d: .079 prompts to attend after- Days Until care appoint- First Use ments, and (Drugs/ receive social Alcohol): reinforcement I: 202.43 (i.e., certifi- (140.46) cates, honor C: 200.74 roll, medal- (136.31) lions). Aver- age cost $270/ d: .012 participant. Percent Ab- Control: stinent from Standard Drugs/ treatment Alcohol: (two sessions I: 48% with addic- C: 49% tion therapists, one during final week of treatment and second in ninth week of after care. Av- erage cost $172/particip ant.

Measures: 12-month follow-up

LIMITATIONS AND FUTURE DIRECTIONS The two biggest issues with research on illicit drugs are their illegality and their addictiveness. Among other things, this adds to the challenge of identifying and working with persons with Drug Use Disorders. While the literature of cost- effective behavioral interventions for excessive alcohol use include evidence for early screening and intervening, research around illicit drugs does not explicitly tackle how to recruit target populations to participate in the interventions.

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Additionally, unlike alcohol or tobacco use, treatment for using illicit drugs is more likely to be mandated by the education, legal, or criminal systems (as it was in some of the studies above).

As discussed earlier, overdose is a significant issue contributing to early mortality due to illicit drug use. In cases where substance use cannot be stopped completely, it might be useful to develop behavioral interventions that target overdose prevention as well. However, it is worth noting that overdose does not always occur due to straightforward causes such as increases in quantity or frequency but can also occur due to less predictable circumstances (e.g., differences in purity of substance, using after a period of abstinence), which may make interventions difficult.

Additionally, continuing care and relapse prevention are important components for sustaining clinical benefits and for which more cost-effectiveness studies are clearly needed. Given the highly addictive nature of these substances, it may take multiple quit attempts to successfully stop use and the temptation to use may persist long after the person has initially stopped using. While many treatment options may include aftercare components, their cost-effectiveness requires further investigation. In at least one youth study and one adult study, the option without the intensive aftercare program turned out to be more cost-effective. However, studies of longer duration are needed to assess how long effects last.

The different illicit drugs (e.g., stimulants vs. sedatives) will likely result in different interventions that prove to be the most cost-effective. Further studies are needed not only to investigate the most economic options for each specific illicit drug but also to tease apart findings from studies that include multiple types of drugs. While addictive outcomes are similar across different substances, the addictive mechanisms may vary. Part of the reason for combining drugs into one study may be due to these similarities; another might be the use of multiple substances simultaneously. While researchers sometimes attempt to identify the “primary” drug of abuse, interactions between multiple substances may have their own impact and influence the best treatment strategies in these cases.

Likewise, the co-occurrence of Drug Use Disorders with other neuropsychiatric disorders is notably high and interventions designed to tackle multiple disorders have a likelihood of cost-effectiveness if they are successfully able to impact multiple health outcomes simultaneously. None of the studies included here focused on these comorbid conditions and how they may or may not influence the efficacy and costs associated with the interventions. For instance, a cognitive behavioral intervention could be simultaneously effective for both decreasing anxiety or depression symptoms and for changing substance use behaviors.

Finally, too many of the studies limited their cost-effectiveness to treatment costs. Given the high societal costs of these disorders, not only through standard measures of lost productivity and earlier mortality, but also on the educational, legal, and criminal justice systems, it seems particularly important to include the broadest payer perspective to truly understand the potential cost-savings of interventions that decrease or stop illicit drug use.

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KEY POINTS Children and Adolescents • For children and adolescents, three studies compared psychosocial interventions with each other, but not to usual care or no care. While a studied intervention may be relatively more cost-effective than its alternatives, it may or may not be more cost-effective than current treatment practices.

• For marijuana use, five treatment options were compared after 12 months. Adolescent Community Reinforcement Approach dominated the other four: Motivational Enhancement Treatment (MET) and low intensity Cognitive Be- havioral Therapy (CBT), MET and high intensity CBT, MET plus high intensity CBT and Family Support Network, and Multidimensional Family Therapy. In second, MET with low intensity CBT dominated the other three.

• For marijuana, alcohol, or both, the combination of Motivational Enhance- ment Therapy (MET) and Cognitive Behavioral Therapy (CBT) was more cost-effective without Assertive Continuing Care (ACC) and than Chestnut's Bloomington Outpatient Treatment with or without ACC after 12 months.

• For illicit substance use (most commonly marijuana), four interventions were similarly clinically effective and did not demonstrate clear cost differences after seven months: Skills-Focused Psychoeducation, Cognitive Behavioral Therapy (CBT), Functional Family Therapy (FFT), or CBT and FFT combined. The options were not compared to usual care or no intervention.

Adults • For adults, only one study each was available for specific illicit drugs (stimulants, benzodiazepines, opiates), and no standardized metrics or willingness to pay thresholds were available to compare across studies.

• For stimulant use disorder, prize-based Contingency Management may be more cost-effective than usual care after 12 weeks for abstinence.

• For long-term benzodiazepine use, tapering alone dominated the combination of tapering and group Cognitive Behavioral Therapy after 18 months. Moreover, tapering alone may be more cost-effective than usual care.

• For opiate use disorder patients receiving methadone maintenance, the cost- effectiveness of different levels of additional psychosocial services was compared. A moderate level of psychosocial care (3 sessions a week) was more cost-effective than both minimal psychosocial care (1 session a week) and enhanced psychosocial care (7 sessions a week).

• For aftercare following intensive treatment, both standard aftercare and Con- tracting, Prompting, and Reinforcing (CPR) aftercare with a behavioral contract, appointment reminders, and social reinforcements, were similarly clini-

264 Illicit Drug Use

cally effective after 12 months. This suggests that the less expensive standard aftercare may be the more cost-effective option.

• Overall, behavioral interventions appear promising for cost-effective solutions but there are insufficient data to draw meaningful conclusions at this time.

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Dennis M, Godley SH, Diamond G, Tims FM, Babor T, Donaldson J, Liddle H, Titus JC, Kaminer Y, Webb C, Hamilton N, Funk R. The Cannabis Youth Treat- ment (CYT) Study: main findings from two randomized trials. J Subst Abuse Treat. 2004 Oct;27(3):197-213.

French MT, Zavala SK, McCollister KE, Waldron HB, Turner CW, Ozechowski TJ. Cost-effectiveness analysis of four interventions for adolescents with a substance use disorder. J Subst Abuse Treat. 2008 Apr;34(3):272-81.

Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, Pickering RP, Kaplan K. (2004a). Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epide- miologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004 Aug;61(8):807-16.

Grant BF, Stinson FS, Dawson DA, Chou SP, Ruan WJ, Pickering RP. (2004b). Co- occurrence of 12-month alcohol and drug use disorders and personality disorders in the United States: results from the National Epidemiologic Survey on Al- cohol and Related Conditions. Arch Gen Psychiatry. 2004 Apr;61(4):361-8. Honarmand K, Tierney MC, O'Connor P, Feinstein A. Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurology. 2011 Mar 29;76(13):1153-60.

Kraft MK, Rothbard AB, Hadley TR, McLellan AT, Asch DA. Are supplementary services provided during methadone maintenance really cost-effective? Am J Psychiatry. 1997 Sep;154(9):1214-9.

Lash SJ, Burden JL, Parker JD, Stephens RS, Budney AJ, Horner RD, Datta S, Jef- freys AS, Grambow SC. Contracting, prompting and reinforcing substance use disorder continuing care. J Subst Abuse Treat. 2013 Apr;44(4):449-56.

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Mark TL, Woody GE, Juday T, Kleber HD. The economic costs of heroin addiction in the United States. Drug Alcohol Depend. 2001 Jan 1;61(2):195-206.

Martín-Sánchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 2009 Nov;10(8):1353-68.

McLellan AT, Arndt IO, Metzger DS, Woody GE, O'Brien CP. The effects of psychosocial services in substance abuse treatment. JAMA. 1993 Apr 21;269(15):1953- 9.

National Drug Intelligence Center (NDIC). National Drug Threat Assessment. Washington, DC: United States Department of Justice; 2014. Retrieved from: http://www.justice.gov/archive/ndic/pubs44/44849/44849p.pdf.

National Institute on Drug Abuse (NIDA). Nationwide Trends Retrieved March 30, 2015, from http://www.drugabuse.gov/publications/drugfacts/nationwide- trends.

Olmstead TA, Sindelar JL, Petry NM. Cost-effectiveness of prize-based incentives for stimulant abusers in outpatient psychosocial treatment programs. Drug Al- cohol Depend. 2007 Mar 16;87(2-3):175-82.

Oude Voshaar RC, Gorgels WJ, Mol AJ, van Balkom AJ, Mulder J, van de Lis- donk EH, Breteler MH, Zitman FG. Long-term outcome of two forms of randomised benzodiazepine discontinuation. 2006b. Br J Psychiatry. 2006 Feb;188:188-9.

Oude Voshaar RC, Krabbe PF, Gorgels WJ, Adang EM, van Balkom AJ, van de Lisdonk EH, Zitman FG. Tapering off benzodiazepines in long-term users: an economic evaluation. 2006a. Pharmacoeconomics. 2006;24(7):683-94.

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266 Disruptive Behaviors

CHAPTER 11: DISRUPTIVE BEHAVIOR DISORDERS IN YOUTH

ABSTRACT Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorders are the most commonly diagnosed and treated Disruptive Behavior Disorders in children and adolescents, with both occurring more commonly in boys than girls. The national childhood prevalence is estimated around 8.7% to 9.5% for ADHD, and around 9.5% for Conduct Disorders. Additionally, up to 50% of children with ADHD may have co-occurring Conduct Disorders. Importantly, Disruptive Behavior Disorders in childhood are strongly correlated with behavioral problems (e.g., substance use, crime, violence) in adulthood. Those with co-occurring ADHD and Conduct Disorders appear to be at greatest risk for these outcomes.

In the United States, direct and indirect costs of ADHD for children and adults were estimated at $143 to $266 billion annually. While no nationally representative data were available for Conduct Disorders, one study estimated additional costs of more than $70,000 per child over seven years. Data from the United Kingdom confirm that Conduct Disorders are one of the most expensive childhood neuropsychiatric disorders, with societal costs ten-fold greater in adulthood. Given these high costs, even expensive interventions may still be cost- saving. Unfortunately, limited cost-effectiveness data are available.

For ADHD in children and adolescents, cost-effectiveness of intensive medication management, a multicomponent behavioral program, or both combined relative to routine care varied depending on co-occurring disorders and willingness to pay thresholds. For Conduct Disorders, stacking multiple components of the Incredible Years Program (Child Training, Parent Training, Teacher Training) had differing cost-effectiveness, with the combination of Parent Training and Teacher Training appearing to be most cost-effective for behavioral problems at school, and the combination of all three appearing to be most cost-effective for behavioral problems at home. Studies limited to the Parent Training component found it had the potential to be more cost-effective than waiting list control, depending on the willingness to pay threshold. For children at-risk for conduct problems, delivering parental training in a community-based large group program may be up to six times more cost-effective than delivering it in clinic-based individual training, but these were not compared to standard care or no intervention.

For juvenile offenders with at least two prior offenses who may have undiagnosed or untreated disorders, Multisystemic Therapy was significantly cost- saving for both taxpayers and victims of crime compared to individual therapy after almost 14 years. Clearly, behavioral interventions for disruptive behavior in childhood can bring immense relief to parents and benefits to children and society across the lifespan, while reducing the economic burden. Given this, more cost-effective interventions are urgently needed.

BACKGROUND ON DISORDER The most commonly diagnosed and treated Disruptive Behavior Disorders in school-aged children are Attention Deficit Hyperactivity Disorder (ADHD) and

267 Disruptive Behaviors

Conduct Disorders. Parents and teachers can play key roles in their prevention, development, persistence, and treatment. Untreated childhood problems can often continue into adulthood. Even when they do not, they still lead to significant consequences.

Attention Deficit Hyperactivity Disorder (ADHD) Attention Deficit Hyperactivity Disorder (ADHD), which is characterized by inattention and/or by hyperactivity and impulsivity, is typically diagnosed in childhood; however, for 43% to 80% it continues after puberty and into the teen- age years (Barkley et al., 1990; Biederman et al., 1996; Mannuzza et al., 1998). ADHD can also be diagnosed in adulthood, although we do not review that here.

Signs of inattention include difficulty sustaining attentive focus, careless mis- takes, appearing not to listen, being easily distracted and forgetful, difficulty organizing and finishing tasks, and tending to lose things. Signs of hyperactivity include being fidgety or squirmy, being unable to stay seated, running or climb- ing in inappropriate situations, and talking incessantly. Signs of impulsivity include difficulty waiting one’s turn, blurting out answers before questions are fin- ished, and interrupting others.

Young people may experience symptoms of inattention or hyperactivity and impulsivity or both. To be diagnosed as ADHD, these symptoms must persist for at least six months, be inappropriate for the child’s age, and cause significant impairments in more than one setting, which could be at school or at home, and includes social, academic, and/or work functioning.

Conduct Disorders Conduct Disorders are only diagnosed in children and adolescents, although similar patterns of behavior can lead to other diagnoses in adulthood. Conduct Disorders are characterized by hostile, angry, aggressive, defiant, disobedient and oppositional behaviors that occur with excessive frequency, severity, and persistence for over six months.

The less severe version is Oppositional Defiant Disorder, which is characterized by frequent loss of temper, defiance, deliberate annoyance of others, argumenta- tiveness, blaming others, and being easily annoyed, angry, resentful, and spite- ful. The more severe version is Conduct Disorder, which includes the symptoms of Oppositional Defiant Disorder as well as a tendency to substantially violate the rights of others or break major societal norms.

These more severe symptoms can include aggression, such as bullying or threatening others, starting physical fights, being physically cruel to people or animals, or using a weapon against others in fights; destruction of property (such as setting fires), theft or lying to obtain things; and serious violations of rules, such as running away from home or skipping school.

In addition to these symptoms, some youth with Conduct Disorder may show little empathy or concern for other people’s feelings and well-being, and tend to show minimal emotion in interactions with others. Those with these additional

268 Disruptive Behaviors characteristics may have a more severe form of Conduct Disorder and require more intensive or individualized treatment.

For some children, Oppositional Defiant Disorder later evolves into Conduct Disorder. Likewise, a subset of children with Conduct Disorder later meet criteria for Antisocial Personality Disorder (see Chapter 5). It has been suggested that these disorders may have similar risk factors or etiology and may be precursors to each other (Loeber et al., 2000; Burke et al., 2002).

Co-Occurring ADHD and Conduct Disorders ADHD and Conduct Disorders commonly co-occur in young people. Evidence suggests that ADHD is associated with earlier onset of Conduct Disorders, and influences the development, progression, and severity of Conduct Disorders. In general, children with both disorders may also experience more severe and persistent disruptive behaviors (Loeber et al., 2000). Most importantly, both ADHD and Conduct Disorders include disruptive behaviors linked to lifelong consequences for both the child’s personal health and the economic burden to society.

Lifelong Impact Research indicates a strong connection between Disruptive Behavior Disorders like ADHD and Conduct Disorders in childhood and neuropsychiatric disorders and behavioral issues (e.g., substance use, crime, violence) in adulthood.

A representative study looking at the effects of childhood Conduct Disorders on ten different neuropsychiatric diagnoses (e.g., depression, schizophrenia, alcohol use) found that increasing numbers of conduct problems in childhood correlated with increasing prevalence for all disorders in adulthood. These increases were particularly evident for externalizing disorders (i.e. behaviors directed outward rather than inward), which suggest that some of the risk factors or behaviors may persist from childhood into adulthood (Robins & Price, 1991).

The continuation of ADHD or conduct problems into adulthood leads to a greater likelihood of incarceration. Multiple longitudinal studies found a correlation between childhood ADHD and adult criminality (Matza et al., 2005) and between childhood Conduct Disorders and adult criminality (Colman et al., 2009). For example, children age 5 to 12 years old who had symptoms of ADHD were more likely to report criminal activities as young adults compared to children without those symptoms (Fletcher & Wolfe, 2009), and a study of almost 4,000 inmates found greater prevalence of ADHD (10.5%) compared to the general population (Cahill et al., 2012).

Children with co-occurring ADHD and Conduct Disorders may be particularly at risk, with a greater likelihood of substance use and criminal activity than children with ADHD alone. In these cases, it has been suggested that Conduct Dis- orders have a greater impact on the delinquent behavior (Jones et al., 2009).

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PREVALENCE OF DISORDER

Attention Deficit Hyperactivity Disorder (ADHD) In the United States, the prevalence for ADHD has been estimated to fall within a wide range from 2% to 26%. Some recent national estimates for ADHD in children center around 9%, with one study estimating 8.7% prevalence (age 8 to 15 years; Froehlich et al., 2007) and another 9.5% diagnoses in 2007 (age 4 to 17 years). ADHD occurs more commonly in boys than girls (11.8% vs. 5.4%; CDC, 2008). One major hindrance to accurate prevalence estimates is the high rates of under-diagnosis or under-treatment. Different researchers may account for this missing information in different ways, which can have a noticeable impact on estimates. By one account, more than 50% of children with ADHD may be undiagnosed or untreated (Froehlich et al., 2007), although rates of diagnosis have increased over the last several decades. This increase in diagnosis is estimated at 3% to 5% between 1997 and 2007 (CDC, 2008).

Although diagnostic criteria were developed for children, ADHD also occurs in adults. The U.S. adult prevalence is estimated at 4.4%. As with children, ADHD occurs more frequently in males than females (Kessler et al., 2006). In both children and adults, ADHD is highly comorbid with other neuropsychiatric disorders, which for children includes Conduct Disorders. In a population of children with ADHD receiving medical services, approximately half of them also had a Conduct Disorder (Cahill et al., 2012).

Conduct Disorders The prevalence of Conduct Disorders has been estimated to fall within a wide range, from 6% to 16% for males and 2% to 9% for females. A recent nationally representative study estimated the lifetime prevalence at 9.5% (Nock et al., 2006). However, prevalence among children already diagnosed with ADHD is much higher at 30% to 50% (Jones et al., 2009). As with ADHD, Conduct Disorders occur more frequently in boys than girls (12.0% vs. 7.1%), and are highly comorbid with other neuropsychiatric disorders (Nock et al., 2006).

ECONOMIC BURDEN OF DISORDER Disruptive Behavior Disorders have a high economic burden throughout the lifespan and across multiple domains including family, education, workplace, legal, and criminal justice systems.

Attention Deficit Hyperactivity Disorder (ADHD) A systemic review estimated U.S. annual direct and indirect costs from ADHD in both children and adults at $143 to $266 billion as of 2010. For adults – both those with ADHD and family members of those with ADHD – most of the costs were indirect costs from productivity and income losses, with total costs estimated at $105 to $194 billion (Doshi et al., 2012).

For children and adolescents, most of the costs were direct costs from healthcare (56% to 61%) and education (35% to 40%), with total costs estimated at $38 to $72 billion (Doshi et al., 2012). A systemic review limited to young people estimated annual costs at $14,576 per young person with ADHD as of 2004. Based on a con-

270 Disruptive Behaviors servative estimate of 5% prevalence, total societal costs were extrapolated to $42.5 billion annually (Pelham et al., 2007). Meanwhile, annual costs of ADHD on the U.S. education system were estimated at $4,689 per student with ADHD. In this case, costs to the U.S. education system were extrapolated to $13.4 billion annually or $174 billion over 13 years of schooling (Robb et al., 2011).

ADHD also impacts family members, in part due to the productivity and income losses described earlier but also due to the family’s own healthcare costs. One study estimated annual direct and indirect costs at $6.78 billion for families of a child with ADHD and $12.1 billion for families with an adult with ADHD (Matza et al., 2005). In general, annual costs for family members were estimated to range from $33 to $43 billion, with approximately 95% from increased healthcare utilization (Doshi et al., 2012). For instance, parents of children with ADHD had up to twice the annual medical costs of parents without children with ADHD.

Overall, these estimates are considered underestimates that only include a subset of associated costs and rarely estimate future costs. For instance, none included costs for commonly co-occurring health issues, such as substance abuse or traffic accidents. Moreover, they do not assess economic consequences of childhood disorders into adulthood such as increased rates of criminal behavior. However, one nationally representative study of adults who had childhood ADHD symptoms estimated that the increased likelihood to engage in criminal activity as young adults cost victims $50 to $70 million and society another $2 to $4 billion annually (Fletcher & Wolfe, 2009).

Conduct Disorders As with many childhood disorders, no nationally representative economic data are available for Conduct Disorders; however, it appears that for co-occurring ADHD and Conduct Disorders, the costs are much greater for the additional Conduct Disorders than for ADHD alone (e.g., Jones et al., 2009).

In the United States, the public sector costs of Conduct Disorders across four poor communities exceeded $70,000 per child over seven years. Notably, costs were significantly greater for Conduct Disorder than for Oppositional Defiant Disorder or elevated conduct symptoms not meeting diagnostic criteria (Foster & Jones, 2005). In general, childhood Conduct Disorders are correlated with increased use of resources throughout the lifetime. In the United Kingdom, social services were used more for children with Conduct Disorders than for other childhood emotional disorders (Shivram et al., 2009). Moreover, one study estimated the societal costs of childhood Conduct Disorders were ten-fold those for children with no conduct problems (Scott et al., 2001).

In fact, Conduct Disorders may be the most expensive childhood neuropsychiatric disorder. While this is often attributed to Depressive Disorders, a study of Medicaid treatment costs in children found depression was more expensive than all neuropsychiatric disorders except for Conduct Disorders. Related, a study of childhood depression with or without co-occurring Conduct Disorders showed childhood depression and co-occurring Conduct Disorders led to higher costs in adulthood while childhood depression alone had no additional costs in adult-

271 Disruptive Behaviors hood (Lynch & Clarke, 2006). Overall, available data point to the immense unmeasured costs incurred by Conduct Disorders in the United States.

CLINICALLY EFFECTIVE INTERVENTIONS

Newborns and Infants Existing literature support the use of behavioral management strategies for addressing sleep problems in infants, toddlers and preschoolers. There are a variety of management strategies with some evidence for effectiveness, but available data are not sufficient to determine the relative effectiveness of these interventions. Recommended strategies include unmodified extinction, extinction with parental presence, and preventive parent education, with some support for graduated extinction, positive routines, and scheduled awakenings (Morgenthaler et al., 2006).

Attention Deficit Hyperactivity Disorder (ADHD) Treatment guidelines for ADHD vary depending on the child’s age, which should be kept in mind when reviewing the interventions below. In general, Be- havior Therapy from a parent or teacher is recommended as first-line treatment at younger ages (4 to 5 years old), although stimulant medications may be used in cases where Behavior Therapy in ineffective or unavailable. Behavior Therapy, stimulant medications, or both combined are recommended for older children and adolescents.

Behavior Therapy encompasses multiple interventions that have been proven effective, which broadly include Behavioral Parenting Training (administered by parents in the home), Behavioral Classroom Management (administered by teachers in the classroom), and Behavioral Peer Interventions (typically group- based interventions, focused on peer interactions). Current data suggest that stimulant medications may have a stronger clinical effect than Behavior Therapy on core symptoms, although some studies show increased benefits for combining medication with Behavior Therapy, including lower medication dosages to obtain similar overall effects (Subcommittee on ADHD, 2011).

Conduct Disorders Treatment guidelines for Conduct Disorders have not been codified to the same extent as for ADHD. General recommendations include behavioral interventions in the same vein as those for ADHD (e.g., structured activities, consistent behavior guidelines) with a focus on positive reinforcement for desirable behaviors and planned ignoring or punishments for undesirable behaviors. This includes training parents on communication skills to effectively enforce these recommendations. No medications are approved for Conduct Disorders specifically, but can be recommended adjunctively for specific symptoms (e.g., aggressiveness, impulsivity) or for co-occurring neuropsychiatric conditions (Searight et al., 2001).

COST-EFFECTIVENESS OF INTERVENTIONS Most studies of Disruptive Behavior Disorders in children and adolescents focused on Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disor- ders. One study also targeted juvenile offenders (some of whom may have undiagnosed or untreated disorders).

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A prior review of behavioral and cognitive behavioral group-based parenting programs for early-onset conduct problems in children (age 3 to 12 years) indicated parent training programs were cost-effective, costing approximately $2,500 more per family than a waiting list control to bring a child with conduct problems into nonclinical range (Furlong et al., 2013). This group-based parenting program focused on both reducing child conduct problems as well as improving parental mental health and parenting skills. Effective behavioral programs vary in terms of whether they focus on modifying parent, educator, or child cognitive and behavioral skills to obtain improvements in child outcomes.

Attention Deficit Hyperactivity Disorder (ADHD) The Multimodal Treatment Study of Children with ADHD, one of the most influential studies on ADHD to date, compared three different interventions: 1) intensive medication management, 2) a multicomponent behavioral treatment targeting multiple aspects of the child’s life, and 3) the medication and behavioral treatments combined. Many of these children had co-occurring conditions including Conduct Disorders: 14% had Anxiety or Depressive Disorder, 30% Op- positional Defiant or Conduct Disorder, and 25% both Anxiety or Depressive Disorder and Oppositional Defiant or Conduct Disorder.

In terms of bringing one additional child to normal functioning at the end of treatment after 14 months, intensive medication management dominated the multicomponent behavioral treatment. However, the behavioral intervention may be more cost-effective than routine community care at $68,128 per additional child brought to normal functioning, depending on the willingness to pay threshold. Meanwhile, the behavioral and medication interventions combined only cost an additional $2,500 over the behavioral intervention alone per additional child brought to normal functioning.

Notably, results varied depending on co-occurring conditions. For ADHD alone, the medication intervention was nearly certain to be cost-effective at all values assigned to achieving normal function, with the combined intervention only cost- effective at higher values. For ADHD and co-occurring Anxiety or Depressive Disorder, the behavioral intervention alone may be more cost-effective at higher values. For ADHD and co-occurring Oppositional Defiant or Conduct Disorder, the medication intervention may be cost-effective at lower values, but the combined intervention was more likely to be cost-effective at higher values. Lastly, for ADHD and both types of co-occurring disorders, only the medication intervention was likely to be cost-effective, and only at low values (Jensen et al., 2005; Foster et al., 2007a). Overall, medication management and multicomponent behavioral treatment alone or in combination all have the potential to be cost- effective, depending on the co-occurring conditions and the value assigned to the improvement.

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Table 2. Behavioral Interventions for Attention Deficit Hyperactivity Disorder (ADHD) Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Jensen et al. 579 children Interventions: Change in Co- PP: Societal (2005) & Fos- (ages 7-9.9 (1) Intensive lumbia Im- ter et al. years) diag- medication pairment Scale ICER (per (2007a) nosed with management (CIS): additional ADHD across for 14 months. ADHD only child with Multimodal 6 sites in U.S. (2) Multicom- I1: -.92 (95% normal func- Treatment 32% ADHD ponent behav- CI, -1.26 to tioning):

Study of only, 14% ioral treat- -.59) I1: $2000360 Children with comorbid ment target- I2: -.70 (95% I2: $200068,128 ADHD com- with internal- ing multiple CI, -1.00 to I3: $200015,993 paring three izing disorder aspects of -.40) I3 vs. I1: treatments (Anxiety or child’s life for I3: -.86 (95% $200055,253 Depression), 14 months. CI, -1.14 to I3 vs. I2:

30% with (3) Combina- -.58) $20002,500 comorbid tion of medi- C: -.60 (95% I2 vs. I1: with external- cation and CI, -.87 to -.34) Dominated izing disorder behavioral ADHD + in- (Conduct or treatment for ternalizing Willingness Oppositional 14 months. I1: -.77 (95% to pay Defiant Dis- CI, -1.26 to threshold: order), 25% Control: -.27) ADHD only with both Routine I2: -1.18 (95% I1 nearly cer- comorbidities. community CI, -1.75 to tain to be care. -.62) most cost- I3: -.71 (95% effective at all Measures: CI, -1.25 to values. At 14 months -.16) somewhat C: -.21 (-.71 to higher values, .29) I3 becomes cost-effective. ADHD + externalizing ADHD + in- I1: -1.14 (95% ternalizing CI, -1.56 to At higher -.73) values, I2 I2: -.88 (95% may be cost- CI, -1.26 to effective. -.49) I3: -1.43 (95% ADHD + ex- CI, -1.85 to ternalizing -1.01) At low val- C: -.93 (95% ues, I1 is CI, -1.23 to more likely to -.62) be cost- effective, but

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness ADHD + both at higher val- comorbidities ues, I3 more I1: -1.37 (95% likely to be CI, -1.88 to cost-effective. -.86) I2: -1.50 (95% ADHD + both CI, -1.97 to comorbidities -1.03) I1 only one I3: -1.59 (95% with proba- CI, -1.92 to bility of cost- -1.26) effectiveness, C: -.78 (95% and only at CI, -1.17 to very low val- -.39) ues.

Conduct Disorders Studies on Conduct Disorders focused on young children considered at-risk or early-onset for conduct problems.

The Incredible Years Program was the subject of an influential series of studies for early-onset conduct problems including Oppositional Defiant Disorder and Conduct Disorder. The Incredible Years Program is a multicomponent early intervention with different components to train children, parents, and teachers. Studies compared whether stacking multiple intervention components was more cost-effective than delivering components separately, and investigated which combinations work best in which settings. Findings were consolidated across six trials over 20 years; some of the trials were quite small. It is worth noting that other groups have adapted the Incredible Years Program for use around the world, and more cost-effectiveness data are available from studies of these adap- tations. Two studies from Wales and Ireland assessed the cost-effectiveness of the Parent Training component for parents of children with clinically significant behavioral problems, at-risk for developing Conduct Disorders.

Overall, if no value were assigned to a behavioral improvement, then none of the components were considered more cost-effective than routine care. For behaviors at school, the combination of Parent Training and Teaching Training was most likely to be cost-effective if the willingness to pay threshold were at least $3,000 per one standard deviation improvement on a measure of school behavior (Prob- lem Behavior Questionnaire). For behaviors at home, the combination of Child, Parent, and Teacher Training was the most cost-effective option but did not exceed 70% likelihood of cost-effectiveness no matter how high the willingness to pay threshold per one standard deviation improvement on a measure of home behavior (Dyadic Parent-Child Interaction Coding System; Foster et al., 2007b; Olchowski et al., 2007).

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Meanwhile, the Incredible Years Parent Training component had the potential to be more cost-effective than waiting list control depending on the willingness to pay threshold, costing £73 (€83) in the study from Wales and €87 in the study from Ireland per incremental improvement in a measure of the intensity of child behavioral problems. If the willingness to pay threshold were £100 in the Irish study, then there was an 83.9% likelihood the Parent Training was more cost- effective than waiting list control, and if it were €115 in the Welsh study, then there was an 80% likelihood. While all participating children scored above the clinical cut-off on the Eyberg Child Behavior Inventory’s Intensity subscale to indicate the intensity of behavioral problems, the Welsh study concluded the intervention seemed more cost-effective for children with higher intensity of behavioral problems (Edwards et al, 2007; O’Neill et al., 2013; McGilloway et al., 2012).

Another study focused on Parent Training for junior kindergarten students considered at-risk for Conduct Disorders in Canada. The training included problem- solving skills, reinforcing positive and ignoring minor disruptive behaviors, and working with children to pre-plan difficult situations utilizing case-based role- playing and active discussion of strategies with homework. The training was offered in two different delivery formats over 12 weeks: community-based large group parent training of approximately 27 participants or clinic-based individual parent training. The community-based group training had greater clinical improvements than the clinic-based individual training and no training after six months. It also cost as less than the clinic-based individual training, with researchers estimating the community-based group program was six times as cost- effective as the clinic-based individual one (Cunningham et al., 1995).

Table 3. Behavioral Interventions for Conduct Disorders Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness O’Neill et al. 132 families Intervention: Eyberg Child PP: Public (2013) & with children Incredible Behavior In- Sector McGilloway (age 3-8 years) Years Pre- ventory et al. (2012) with clinically school/Early (ECBI): ICER (per 1- significant Years Parent Intensity sub- point im- Incredible conduct prob- Training (PT) scale provement in Years Parent lems in Ire- program with I: 121.3 (40.7) ECBI Intensity Training Pro- land. 93 par- weekly 2-hour C: 144.9 (33.2) score): gram in Ire- ents in inter- group ses- (p<.001) €87 land vention, 39 sions (~12 d: .639 parents in people) for 12- Willingness to control. 14 weeks. Av- Problem sub- pay threshold: erage cost scale If value is €1,463/child. I: 11.6 (9.0) €115 per in- C: 17.6 (8.4) cremental im- Control: (p<.001) provement, Waiting list. d: .690 80% probability Parent Measures: Difference (C Training is

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness 6 months minus I) more cost- 20.33 effective than waiting list. If Percent Non- value is €137 Clinical After to €158, 90% Intervention to 95% proba- (ECBI<127): bility. I: 60% C: 35% It would cost €9,483 to bring the child with the highest intensity score to below the clinical cut-off point and €2,784 to bring the average child below this limit. Edwards et al. 116 families Intervention: Eyberg Child PP: Public (2007) with children Incredible Behavior In- Sector (age 36-59 Years Pre- ventory Incredible months) with school/Early (ECBI): Years Parent clinically sig- Years Parent Intensity sub- ICER (per 1- Training Pro- nificant be- Training (PT) scale point im- gram in Wales havioral prob- program with I: 117.17 provement in lems in Wales. weekly group (35.99) ECBI Intensity 73 parents in sessions (8 C: 140.74 score): intervention, people). Av- (40.77) £73 43 parents in erage cost d: .614 control. £1,934/child. Willingness to Problem sub- pay threshold: Control: scale If value is Waiting list. I: 12.09 (9.83) £100 per in- C: 12.95 cremental im- Measures: (10.87) provement, 6 months d: .083 83.9% probability Parent Percent Non- Training is Clinical After more cost- Intervention effective than (ECBI<127): waiting list. I: 62% C: 42% It would cost £5,486 to bring the child with

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness the highest intensity score to below the clinical cut-off point and £1,344 to bring the average child below this limit. Foster et al. 459 children Incredible Change in PP: Treatment (2007b) & Ol- (ages 3-8 Years treatment Problem Be- chowski et al. years) with components to havior Ques- Total Cost (2007) Conduct Dis- improve behav- tionnaire (per child):

orders across ior in different (PBQ) at I1: $20031,164 Incredible 6 different settings: Child school: I2: $20031,579 Years Pro- clinical trials Training (CT), I1: -2.24 (6.13) I3: $20032,713 gram target- spanning 20 Parent Train- (p=.01) I4: $20031,868 ing multiple years in U.S. ing (PT), and I2: -1.80 (6.87) I5: $20031,454 settings for 76.7% male. Teacher Train- (p=.00) I6: $20033,003 Conduct Dis- 54 in intervening (TT). I3: -3.13 (7.23) orders tion #1, 292 in Interventions: (p=.02) ICER (per 1- intervention (1) CT only. I4: -5.17 (6.84) SD improve- #2, 38 in in- Average cost (p=.00) ment in PBQ): tervention #3, $1,164/child. I5: -2.25 (7.16) I1 and I5 24 in interven- (2) PT only. (NS) dominate I2, tion #4, 11 in Average cost I6: 1.50 (7.28) I4 and I6. intervention $1,579/child. (NS) Control not #5, 19 in in- (3) CT + PT. C: N/A compared. tervention #6, Average cost 21 in control. $2,713/child. d: Not calcu- ICER (per 1- (4) PT + TT. lable as no SD improve- Average cost control ment in $1,868/child. DPICS-R): (5) CT + TT. Change in I6 dominates Average cost Negative I1-I5. $1,454/child. Child Behav- Control not (6) CT + PT + ior Score compared. TT. Average (DPICS-R) at cost $3,003/ home: Willingness to child. I1: .36 (2.38) pay threshold: (NS) If no value per Control: I2: -.06 (2.94) improvement, No interven- (NS) control most tion. I3: -.84 (3.45) likely to be (NS) cost-effective. Measures: I4: -.48 (3.54) For behavior Post- (NS) at school, if

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Treatment I5: -.58 (1.51) value is $3K/ (NS) 1-SD im- I6: -2.51 provement in (10.28) PBQ, com- (NS) bined Parent C: 1.80 (2.97) Training and (p=.01) Teacher Train- ing most cost- d1: .538 effective. For d2: .629 behavior at d3: .822 home, no mat- d4: .700 ter how high d5: 1.063 value per 1- d6: .651 SD improvement in DPICS-R, max. 70% probability combined Child, Parent, and Teacher Training most cost-effective. Cunningham 114 families Interventions: Parental Prob- PP: Treatment et al. (1995) with junior Coping model- lem-Solving kindergarten ing problem Skills: Program Parent train- children con- solving ap- I1: 19.8 (6.8) Costs (per ing programs sidered at-risk proach to skill I2: 21.5 (5.3) family): for families of for Disruptive acquisition: C: 17.3 (5.5) I1: $5.42 preschoolers Behavior Dis- (1) 12-week I2: $5.92 at-risk for orders (≥90% clinic-based d1: .407 Disruptive percentile on individual d2: .778 Costs In- Behavior Dis- parent-rated parent train- d3 (I1 vs. I2): curred (by orders home behaving. .406 family): ior question- (2) 12-week I1: $89.04 naire) in Can- community- Change in I2: $39.60 ada. No offi- based large Home Situa- cial diagnosis. group parent tions Ques- Personnel 36 in interven- training. Av- tionnaire: Costs (per tion #11, 35 in erage 27 par- I1: .37 (1.4) Session): intervention ticipants (~18 I2: 1.16 (1.2) Per family #2, 43 in con- families). C: .51 (1.3) I1: $58.79 trol. (p=.03) Control: Per group Waiting list. d1: .104 I2: $169.81 d2: .520

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Measures: d3 (I1 vs. I2): No formal cost- 6-month fol- .608 effectiveness low-up analysis, but Total Nega- community- tive Child Be- based group havior: format estimat- I1: 22.0 (22.1) ed to be 6x as I2: 16.5 (19.2) cost-effective as C: 14.6 (13.4) clinic-based individual for- d1: .417 mat. d2: .117 d3 (I1 vs. I2): .266

Juvenile Offenders Lastly, a study of juvenile offenders with at least two prior arrests compared the cost-effectiveness of two therapy treatments to prevent recidivism (i.e. return to crime) and, in turn, decrease associated societal costs. Both treatments were offered on average for between 20 to 25 hours. After almost 14 years, Multisystemic Therapy (MST), which included therapists working within schools, homes, and neighborhoods to offer services to the youth and their caregivers in settings and at times convenient to the family, was found to have significant reductions in crime as well as significant cost benefits from the perspective of both taxpayers and the victims of crime compared to individual therapy that focused only on the youth. Overall, the intervention saved both direct and indirect losses totaling $9.51 to $23.95 per dollar spent on MST or $75,110 to $199,374 per individual who received MST (Klietz et al., 2010; Schaeffer et al., 2005).

Table 4. Behavioral Interventions for Juvenile Offenders Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Klietz et al. 176 juvenile Intervention: Recidivism PP: Societal (2010) & offenders Multisystemic Rate: Schaeffer et al. (average age Therapy with I: 50% Taxpayer Ex- (2005) 14.5 years at services deliv- C: 81% penses (per treatment, ered to youth (p<.0001) arrest):

Multisystemic 28.8 years at and their I: $200855,046 Therapy with follow-up) caregivers in Number of C: $200843,277 serious and with at least settings and at Offenses: violent juve- two prior ar- times conven- I: 1.82 (3.24) Crime Victim nile offenders rests for crim- ient to family. C: 3.96 (4.30) Expenses (per inal offenses. Average 20.7 d: .568 arrest): 69.3% male. hours of Direct costs

92 in interven- treatment. Number of I: $20083,217 tion, 84 in Days Sen- C: $20082,194

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness control. Control: tenced to Con- Individual finement: Indirect costs

Therapy with I: 582.25 I: $200837,907 usual com- (2,843.84) C: $200823,964 munity out- C: 1,356.53 reach treat- (3,120.10) Difference in ment for ju- d: .260 Crime Victim venile offend- Avoided Ex- ers. Focus on Number of penses (per individual Days Sen- participant): youth rather tenced to Pro- Direct savings

than their sys- bation: $200856,910 tems. Average I: 420.97 Indirect sav- 22.5 hours of (945.72) ings

treatment. C: 738.71 I$200893,022 (1,353.19) Measures: d: .276 Net Benefit to 13.7 year fol- Taxpayers low-up 54% fewer ar- and Crime rests and 57% Victims:

fewer days in- $200875,110 to carcerated. $2008199,374

LIMITATIONS AND FUTURE DIRECTIONS Cost-effectiveness studies to alleviate disruptive behaviors in youth are limited, requiring replication to confirm robustness of findings. Further, limited comparisons of behavioral interventions to medication or usual care make it difficult to ascertain overall cost-effectiveness. Additional studies comparing the different interventions with each other, to stimulant medications, and to usual care are all needed. Additionally, current data suggest additional analyses will be needed depending on specific symptoms, co-occurring disorders, and delivery settings.

Clearly, the frequent co-occurrence between ADHD and Conduct Disorders and correspondingly worse outcomes warrant further studies targeting this population, including ways that treatment strategies could target both simultaneously to maximize cost-effectiveness. Additionally, certain behavioral traits that do not meet diagnostic criteria for these disorders (e.g., antisocial behavior) and specific behavioral outcomes associated with these disorders (e.g., higher likelihood of substance use and accidents) could all be targeted by behavioral interventions as well. Prevention or early intervention for preliminary symptoms or related behaviors appears to provide a viable opportunity for curtailing lifelong costs.

Disruptive Behavior Disorders are particularly complex given their impact across multiple domains and across the lifespan. These disorders have a substantial impact on families, including economic trade-offs both in terms of additional time needed to attend to the child’s needs (e.g., leaving work early to pick up a sus-

281 Disruptive Behaviors pended child) as well as consequences for the family member’s own health (e.g., increased stress leading to substance use). This financial impact is likely extended to the employers of the family members due to parents’ decreased productivity or increased absenteeism. These childhood disorders clearly impact academic success, employment opportunities, criminal behaviors, and related health outcomes across the lifespan. In this case, including the costs to the educational system are as important as the costs to the healthcare system, since many of the treatment opportunities and economic consequences occur in the classroom. Likewise, the costs on the criminal justice system, especially in cases where the behavior disorders go undiagnosed, are also important.

From the early impact of behavioral problems in infancy, into childhood, adolescence, and adulthood, it is clear that current assessments do not adequately capture the economic impact throughout the lifespan. More longitudinal studies of interventions implemented in childhood and continuing through adulthood would also be informative for overall cost-effectiveness. For instance, the study of juvenile offenders reveals how an intervention of only 20 to 25 hours can have long-lasting effects up to 14 years later. Cost-effectiveness solutions may already exist, but more studies are needed to demonstrate these effects.

KEY POINTS • Very limited cost-effectiveness data is available, and most key points supported only by single studies.

• For ADHD in children and adolescents, intensive medication management dominated a multicomponent behavioral treatment in terms of bringing one additional child to normal functioning after 14 months. However, further analyses revealed that cost-effectiveness between the medication intervention, behavioral intervention, or both combined all had the potential to be cost-effective compared to each other or relative to usual care depending on the co-occurring conditions experienced by the child and the willingness to pay threshold.

• For early-onset conduct problems in children and adolescents, combining multiple treatment components appeared to be more cost-effective than the individual components alone. For behaviors at school, combining Parent Training and Teaching Training appeared to be most cost-effective. For behaviors at home, combining Child Training, Parent Training, and Teaching Training appeared to be most cost-effective. The Parent Training also appeared to be more cost-effective at improving the intensity of behavioral symptoms compared to waiting list control across two studies. Cost- effectiveness would depend on the willingness to pay threshold.

• For junior kindergarten students at-risk for Conduct Disorders, delivering Parent Training via a community-based large group program appeared to be up to six times more cost-effective than clinical-based individual training after six months, although it would still need to be compared to routine care or no intervention to draw a definitive conclusion on cost-effectiveness.

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• For juvenile offenders with at least two prior offenses who may have undiagnosed or untreated Disruptive Behavioral Disorders, Multisystemic Therapy was significantly cost-saving from the perspective of both taxpayers and victims of crime compared to individual therapy after almost 14 years.

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Furlong M, McGilloway S, Bywater T, Hutchings J, Smith SM, Donnelly M. Cochrane review: behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years (Review). Evid Based Child Health. 2013 Mar 7;8(2):318-692.

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Morgenthaler TI1, Owens J, Alessi C, Boehlecke B, Brown TM, Coleman J Jr, Friedman L, Kapur VK, Lee-Chiong T, Pancer J, Swick TJ; American Academy of Sleep Medicine. Practice parameters for behavioral treatment of bedtime problems and night wakings in infants and young children. Sleep. 2006 Oct;29(10):1277-81.

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Subcommittee on Attention-Deficit/Hyperactivity Disorder; Steering Committee on Quality Improvement and Management, Wolraich M, Brown L, Brown RT, DuPaul G, Earls M, Feldman HM, Ganiats TG, Kaplanek B, Meyer B, Perrin J, Pierce K, Reiff M, Stein MT, Visser S. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011 Nov;128(5):1007-22.

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CHAPTER 12: LIFESTYLE INTERVENTIONS FOR HEALTHY WEIGHT

ABSTRACT Maintaining healthy weight is an important measure of health; being overweight or obese is linked to higher risk for a range of negative health outcomes including heart disease, stroke, hypertension, type 2 diabetes, and some cancers. In the United States, more than two-thirds of the adult population is overweight and more than one-third is obese. In children, approximately 32% are overweight and 17% are obese, increasing risk for adulthood obesity and early onset of metabolic disorders.

The annual economic burden of obesity was estimated at $215 billion including direct medical costs, productivity costs, transportation costs, and human capital costs. In almost all cases, recommended treatment includes reducing caloric intake, increasing physical activity, and incorporating behavioral strategies. For children, recommendations also include family-based treatment to incorporate parents and caregivers. Family-based treatment limited to group sessions was more cost-effective than both group and individual sessions; further, joint group sessions with children and parents meeting together were more cost-effective than children and parents meeting separately. For adults, behavioral weight management programs often compared intensity levels and delivery mechanisms. For three in-person interventions, a group behavioral weight management program was more cost-effective than a waiting list in overweight or obese low- income women, a high-intensity intervention was more cost-effective than a low- intensity version in couples who recently moved in together, and behavioral skills training was more cost-effective than structured exercise training for increasing physical activity in sedentary adults. Telehealth interventions were common in trials, and included delivery by mail, phone, Internet, and television. A mail-based intervention with support from a health counselor was equally cost-effective to usual care and more cost-effective than the phone-based version. A group-based telephone intervention dominated the individual-based version for rural women, but only for those who completed the intervention. An Inter- net-based group weight management program was less cost-effective than the in- person version. However, an Internet-based program for active duty Air Force personnel had the potential to be more cost-effective than usual care, depending on the willingness to pay threshold. Related, an Internet-based program for non- active military personnel and their families was similarly clinically effective at three different intensities, but the most intensive version (including Motivational Interviewing-based coaching) was most cost-effective. Finally, a videotaped version of a weight management group had the potential to be more cost-effective than attending the weight loss group in person given the lower costs. For older adults (including survivors of colorectal cancer), personalized newsletters, brief phone-based Motivational Interviewing, or the combination of both, all had limited clinical efficacy and thus appeared similarly cost-effective. Importantly, few studies compared interventions to usual care or no care and few studies compared in-person and telehealth interventions to each other, making it difficult to draw broad conclusions.

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BACKGROUND ON OBESITY Weight can be a useful proxy for health. One of the most common measures of healthy weight is body mass index (BMI), defined as weight (in kilograms) divided by height (in meters squared). Generally, persons outside the normal range for BMI are at greater risk for health problems, although there are always excep- tions. A BMI in the range between 18.5 and 24.9 is typically considered healthy; less than 18.5 is considered underweight, between 25 and 29.9 is considered overweight, and over 30 is considered obese. Another measure of healthy weight is waist circumference, with people outside the normal range at greater risk for diabetes, hypertension, and cardiovascular disease. Unhealthy waist circumference is defined as a waist more than 40 inches (102 cm) around for men, and more than 35 inches (88 cm) around for women. There is no perfect measure of healthy weight, and other measures are needed to indicate overall health (e.g., cholesterol levels, cardiovascular fitness, caloric intake, physical activity).

Obesity in youth is a risk factor for obesity in adulthood, and obesity at any age is a risk factor for multiple negative health outcomes. This increased risk includes heart disease (e.g., arterial plaque build up leading to chest pain, heart attack, or heart failure), stroke (e.g., plaque build up leading to rupture and blood clots in the brain), hypertension (i.e. high blood pressure), type 2 diabetes (i.e. blood sugar dysregulation), osteoarthritis (i.e. joint pain, commonly in the knees, hips, and lower back), sleep apnea and breathing problems, reproductive problems, certain cancers, and more. Additionally, obesity has a stronger association with reduced health-related quality of life than both excessive alcohol use and smoking, including a higher occurrence of chronic medical conditions and increased healthcare and medication spending (Sturm, 2002).

Increasing physical activity and improving eating habits can lead to additional health benefits beyond weight management. In addition to reducing risk for negative health outcomes, increasing physical activity and healthy eating habits can also improve other health outcomes. For example, physical activity that increases heart rate can contribute to cardiovascular fitness and healthy eating that decreases fat intake can improve cholesterol levels. The beneficial effects of weight management on co-morbid health conditions and other health and quality of life outcomes may be particularly relevant to economic analyses, and it is difficult to quantify the full extent of these beneficial outcomes. Most cost-effectiveness studies do not attempt to measure these additional benefits and thus generate conservative estimates of cost-effectiveness.

PREVALENCE OF OBESITY In the United States, more than a third (34.9%) of adults are obese and more than two-thirds (68.5%) of adults are overweight as of 2012. Obesity is also of growing concern for children and adolescents, with 16.9% obese and 31.8% overweight as of 2012 (Ogden et al., 2014). Data suggest first incidence of obesity now occurs at earlier ages, with a recent review concluding that among those who become obese between age 5 and 14, the age at which they meet unhealthy weight criteria is decreasing (Cunningham et al., 2014). In other words, obese children are becoming obese at younger ages. For many years, rising rates of obesity were a major concern. From 2003-2004 to 2011-2012, however, the rates remained stable for

288 Weight Management both youth and adults (Ogden et al., 2014). The prevention of further increases in the obesity rate is a promising start, but rates need to decline to curtail this nationwide epidemic.

ECONOMIC BURDEN OF OBESITY A review of four main sources of economic burden (direct medical costs, productivity costs, transportation costs, human capital costs) estimated that obesity in the United States cost more than $215 billion annually, including $147 billion for adults and $14.3 billion for children in direct medical costs, and up to $66 billion in productivity costs (Hammond & Levine, 2010). Another review estimated direct annual medical costs at $266 per person who is overweight and $1,723 per person who is obese ($1,023 for both combined). Overall, obesity was estimated to cost $113.9 billion annually in direct medical costs. These estimates of direct medical costs are equivalent to 4.8% of national healthcare spending in 2008 (Tsai et al., 2011). Related, the economic burden of direct medical costs due to physical inactivity was estimated to be between $24 billion to $29.2 billion annually (Pratt et al., 2014).

Importantly, because obesity increases risk for other medical conditions, it also contributes to the economic burden of those disorders. As one example, the economic burden of diabetes in the United States was $245 billion as of 2012, with medical expenditures on average 2.3 times higher for those with diabetes than those without (American Diabetes Association, 2013). As another example, the prevalence of hip osteoarthritis is rising due to both increased longevity and increased obesity, and is expected to grow by 174% by 2030, thus adding to obesity’s overall economic burden (Nho et al., 2013).

CLINICALLY EFFECTIVE INTERVENTIONS Treatment guidelines for weight management are relatively straightforward. Be- havioral interventions focus on lifestyle changes, including healthy eating, physical activity, or both combined, based on the evidence that these habits typically drive healthy weight. There are also a few pharmaceutical or surgical options for extremely obese individuals who are considered high risk; however, recommended treatment for both children and adults center on behavioral weight management programs that simultaneously combine decreased caloric intake, increased physical activity, and behavior therapy strategies.

Dietary Therapy can include the modification of caloric intake and/or promotion of changes in dietary practice such as decreasing fat intake and increasing consumption of fruits and vegetables. Physical Activity can have both direct and indirect benefits, including increasing energy expenditure and decreasing body fat, but should be increased slowly with a long-term goal of at least 30 minutes of moderate physical activity on most days. Behavioral Therapy provides skills to support adherence to diet and activity goals. These skills include cognitive restructuring, problem-solving, self-monitoring, stress management, contingency management, and social support.

For children, Family-Based Treatment incorporates parents or primary caretakers into the weight management program. Involving caretakers as well as parents is

289 Weight Management also recommended since care-takers may be able to help influence a child’s diet and physical activity. Family-Based Treatment can include parent education, joint weight management programs for parents and children together, understanding and modifying parenting styles and family dynamics, and/or providing family psychoeducation or therapy more generally.

Pharmacotherapy with the Federal Drug Administration (FDA)-approved sibu- tramine or orlistat is only recommended in addition to behavioral weight management if the person has a BMI equal to or greater than 30 (or equal to or greater than 27 if they have other co-occurring diseases or risk factors) and the person has not experienced weight loss in the behavioral weight management program alone after six months. As these medications have significant side effects, they should only be recommended when other treatment options are unsuccessful.

Weight loss surgery is only recommended for those who qualify clinically as se- verely obese (i.e. BMI equal to or greater than 40, or equal to or greater than 35 with other co-occurring conditions). To date, it remains unknown whether the benefits of weight loss surgery will outweigh the risks over time. It is the patient’s responsibility to be informed and consult with medical professionals before choosing this option.

COST-EFFECTIVENESS OF INTERVENTIONS For weight management, many studies use the measure of “life year” instead of “quality-adjusted life year” (QALY). In other words, the studies only consider benefits related to prolongation of life without adjusting for potential improvements or decrements in quality of life. The standard threshold of $50,000 per QALY appears to have a similar equivalent of $35,000 to $50,000 per additional life year (Hlatky, 2002). Additionally, some studies measure the cost per unit of weight loss (e.g., per pound or kilogram lost). However, the range of acceptable costs considered in the literature varies widely for this metric (e.g., $10 to $133 per pound lost; Gustafson et al., 2009). Finally, studies often include measures of ACER as well as ICER; while the ICER measures the relative difference in cost per improvement between two different interventions, the ACER (average cost- effectiveness ratio) measures the cost per improvement for a single intervention without comparison to another intervention.

Weight Management in Children and Parents Two studies from the same set of researchers assessed cost-effectiveness of family-based treatment, including diet, exercise, and behavior therapy for weight management in children and participating parents, delivered via different formats. In one of 24 families, the standard combination of both group and individual treatment cost approximately 2.8 times as much as group-only treatment with parents and children in separate groups. Both interventions were clinically effective, but the group-only treatment was associated with significantly larger decreases in percentage overweight per dollar spent and in BMI per dollar spent, suggesting the group-only intervention was more cost-effective than the combined one (Goldfield et al., 2001).

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In the second study, the standard family-based treatment of children and parents receiving treatment in separate groups was compared to parents and children receiving treatment together in joint groups, with the only major difference that the joint program also included training on parenting skills. This joint group treatment led to greater clinical improvements in percentage above average BMI for age and gender for children and in number of pounds lost for participating parents after 12 months. The joint group intervention also had lower costs whether the separate parent and child sessions were offered on the same day or separate days. Thus, treating children and parents together led to lower costs per incremental improvement in both the child and adult weight measures and could be considered dominant (Epstein et al., 2014).

Table 1. Behavioral Interventions for Weight Management in Children and Parents Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Epstein et al. 50 over- Interventions: Change in PP: Societal (2014) weight/obese Family-based Percent Over children (age treatment with population ACER (per Family-based 8-12 years) fifteen 60- average BMI percent over group treat- with over- minute group for Child: average BMI ment for child weight/obese sessions (12 I1: −6.9% lost for child): and parental parents. 26 in weekly, 2 bi- I2: −2.2% I1: $209.17 obesity intervention weekly, 2 fol- I2a: $1,036.50 #1, 24 in in- low-up) includ- Change in I2b: $973.98 tervention #2. ing diet, exer- Pounds Lost cise, and behav- for Parent: ACER (per ioral therapy. I1: −10.9 pound lost for (1) Group I2: −6.1 parent): treatment for I1: $132.97 children and I2a: $373.53 parents to- I2b: $351.00 gether. (2) Separate I2a based on if group treat- parent and ments for par- child available ent and child. on separate days, and I2b if Measures: available on the 12 months same day. Goldfield et 24 families Interventions: Change in PP: Treatment al. (2001) with mildly to Family-based Percentage moderately behavioral Overweight: Change in Family-based obese children treatment with Children Percentage treatment for (age 8-12 thirteen 60- 8.04% (10.27) Overweight childhood years). 18/24 minute sessions Units (per obesity parents obese. (8 weekly, 4 Parents dollar spent): biweekly, 1 5.31% (14.13) I1: .014 monthly). I2: .005

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness (1) Separate Obese Parents (p<.05) group treat- 5.70% (16.08) ments for par- Change in ent and child. Change in BMI Unit (per Cost $491.48/ BMI Units: dollar spent): family. Children I1: 0.001 (2) Group and .64 (.63) I2: .0004 individual (p<.01) sessions for Parents parent and .29 (.78) ACER (per child: 15-20 Obese Parents percent minute indi- .31 (.88) change in vidual ses- overweight sions plus 40- Clinical results units): minute group by intervention I1: $71 sessions. Cost not provided. I2: $200 $1,390.72/fam ily. ACER (per change in BMI Measures: units): 12-month fol- I1: $1,000 low-up I2: $2,500

Weight Management in Adults For adults, most interventions are behavioral weight management programs focused both on healthy eating and physical activity, sometimes including a cognitive aspect, typically targeting adults who are already overweight or obese. Cost- effectiveness studies also compare a range of delivery mechanisms including in- person and via mail, phone, Internet, and television.

While not the focus of this chapter, a review found that weight loss surgery (specifically, laparoscopic adjustable banding) was more cost-effective than non- surgical alternatives for persons with mild or moderate obesity and co-occurring type 2 diabetes, but not for persons with obesity alone (Picot et al., 2012).

In-Person Interventions Only three trials tested in-person behavioral weight management interventions, with each targeting a different population (sedentary adults, couples who recently started living together, low-income women). Notably, the first two were focused more on prevention while only the last one specifically targeted an already overweight population.

Sedentary behavior is a known risk factor for morbidity and mortality, so one behavioral skills training intervention targeted increasing physical activity in healthy but sedentary adults. After two years, the behavioral intervention was equally effective as a standard structured exercise training intervention at im-

292 Weight Management proving physical activity, cardiorespiratory fitness, and blood pressure, but the behavioral skills training cost less per participant per month ($17.15 versus $49.31), leading it to be the more cost-effective option for most of the measured health outcomes. For example, the cost per month per additional incremental energy expenditure was $20 for the behavioral intervention and $71 for the structured exercise intervention. In fact, the structured exercise intervention led to slight weight gain, such that the cost per month per additional incremental kilogram lost was $343 for the behavioral intervention but actually cost $71 per kilogram gained in the structured exercise intervention (Sevick et al., 2000)

Similarly, based on the premise that couples first living together may experience decreased physical activity and altered eating habits, one behavioral intervention targeted couples who had recently begun to live together in Australia. The intervention consisted of modules on nutrition, physical activity, and a healthy lifestyle to target potential sedentary behavior, offered at two intensity levels. The low-level intervention included one in-person introductory group session followed by mailed modules. The high-level intervention alternated between in- person group sessions and mailed modules. After one year, physical activity, diet, and blood cholesterol had improved in both versions compared to the waiting list control, but more so in the high-level version. Notably, the costs were not significantly different, only costing an additional $1.84 per participant to achieve an incremental improvement in the health-related outcomes in the high-level version compared to low-level one, indicating the high-level intervention would be the more cost-effective option. However, it is worth noting that some of the specific health outcomes were marginally worse in the high-level intervention than the low-level one (Dzator et al., 2004).

Lastly, for low-income women who are overweight or obese, an in-person behavioral weight management program including weekly group sessions and a contingency management program was more cost-effective than a waiting list control after 16 weeks. The intervention focused on healthy eating and physical activity and provided incentives for attendance and behavioral change goals, while only costing $61 per each additional kilogram lost and $733 to $1,863 per additional life year gained, the latter of which is well within standard willingness to pay thresholds (Gustafson et al., 2009). However, studies of longer duration are warranted, especially to see if the behavior change persists once the incentives are no longer available.

Table 2. Behavioral In-Person Interventions for Weight Management in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Gustafson et 143 low- Intervention: Weight (kg): PP: al. (2009) income wom- Weight-Wise I: 88.2 Healthcare en (age 40-64 behavioral C: 91.4 Weight-Wise years; BMI 25- weight loss ICER (per Life weight loss 45). 72 in in- program with BMI: Year): intervention tervention, 71 weekly 2-hour I: 33.1 $733 to 1,862 for lowin control. group ses- C: 34.5

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness income wom- sions alternat- ICER (per 1- en ing between Blood Pres- additional kg healthy eating sure: lost): and physical Systolic $61 activity for 16 I: 118.5 weeks. Incen- C: 126.5 Willingness to tives for at- pay threshold: tendance and Diastolic Up to value of meeting be- I: 78.5 $14K/Life havior change C: 81.6 Year, Weight- goals. Total Wise interven- cost $242/ Cholesterol: tion remains participant. Total more cost- Control: I: 200.1 effective than Waitlist. C: 206.1 waiting list.

Measures: HDL 16 weeks I: 54.3 C: 52.1 Dzator et al. 137 couples Interventions: Mean Change PP: Interven- (2004) cohabitating 6 modules on in BMI: tion for the first nutrition, phys- I1: .2 (SE .1) Interactive time in Aus- ical activity, I2: .1 (SE .1) ICER (per in- group ses- tralia. 47 in and a healthy C: .3 (SE .1) cremental sions for intervention lifestyle over 16 change in out- weight man- #1, 47 in in- weeks. Mean Change come varia- agement in tervention #2, (1) Low-level in Fitness Ad- bles): couples be- 43 in control. intervention justed for $1.84 ginning to live with 1 in- Body Weight together person group (W/kg): ICER (per in- session, then I1: -.03 (SE .02) cremental mailed mod- I2: .04 (SE .02) change in ules every 2-3 C: -.02 (SE .02) BMI): weeks. $18.30 $38.22/partici Mean Change pant/month. in Exercise ICER (per in- (2) High-level Days (per cremental intervention week): change in Fit- with alternat- I1: .5 (SE .2) ness Adjusted ing mailings I2: .3 (SE .2) for Body and interac- C: .3 (SE .2) Weight): tive group $26.10 per sessions (ap- Mean Change worse out- prox. 8 cou- in Energy come ples/group). (MJ): $38.37/partici I1: -.4 (SE .1) ICER (per in-

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness pant/month. I2: -.9 (SE .2) cremental C: -.7 (SE .2) change in Ex- Control: ercise Days): Waitlist. Mean Change $9.15 per in Fruits and worse out- Measures: Vegetables come 12-month fol- (serves per low-up day): ICER (per in- I1: -.1 (SE .2) cremental I2: .1 (SE .2) change in En- C: -.1 (SE .2) ergy): $3.66

ICER (per incremental change in Fruits and Vegetables): $9.15 per worse outcome Sevick et al. 190 healthy Interventions: Change in En- PP: 2000 (>140% of 6-month in- ergy Expendi- Healthcare ideal body tense phase fol- ture Comparing weight), sed- lowed by 18- (kcl/kg/day): ACER (per lifestyle and entary adults month tapered I1: .84 additional structured ex- (age 35-60 maintenance I2: .69 kcal/kg/day ercise inter- years) in the phase. in month): ventions U.S. 100 in in- (1) Behavioral Change in Change in En- (Project tervention #1, skills training Moderate Ac- ergy Expendi- ACTIVE) 90 in interven- to increase tivity ture tion #2. physical activ- (kcl/kg/day): I1: $20 ity in daily I1: .93 I2: $71 lives with I2: .33 weekly/bi- Change in weekly group Change in Moderate Ac- sessions then Weight (kg): tivity maintenance. I1: .05 I1: $18 Monthly cost I2: -.69 I2: $149 $17.15/partici pant. Both interven- ACER (per (2) Structured tions were simi- additional kg exercise train- larly effective of weight lost ing with su- for most clini- in month): pervised in- cal outcomes. I1: $343 tense exercise I2: -$71

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness for 20-60 minutes then Lifestyle inter- maintenance vention ap- with referral peared to be to local fitness more cost- facilities. effective that Monthly cost structured ex- $49.31/partici ercise interven- pant. tion.

Measures: 24 months

Telehealth Interventions: Mail and Phone One intervention compared mail- and telephone-based interventions, and another compared a telephone-based intervention delivered in groups or for individuals.

In a study of approximately 1,800 individuals who were overweight or obese and in a managed care setting, a telehealth intervention of ten sequential interactive lessons for diet and physical activity and supported by a health counselor was offered by mail or telephone. In the mail-based version, participants were mailed individual lessons, returned them back for feedback, and then were mailed further guidance and the next lesson. In the phone-based version, participants still received all of the lessons by mail but then scheduled a series of guidance phone calls. After two years, there were no clinical differences between the two interventions or usual care; however, the level of participation (i.e. number of completed lessons) was a strong predictor of outcomes. Significantly more participants started the mail-based treatment than the phone-based one (88% versus 69%), but significantly more lessons were completed in the phone-based intervention than the mail-based version (7.2 versus 2.3). Overall, average cost- effectiveness per additional kilogram of weight loss was similar for usual care ($71.50) and the mail-based version ($72.08), and almost double for the phone- based version ($132.70; Sherwood et al., 2006).

For rural women, a population identified as being sedentary and having high rates of obesity, a pilot comparison of telephone-based treatment delivered in either a group or individual format found the group intervention dominated the individual one for the subset of participants who completed the treatment. How- ever, these findings were not significant when including those who did not complete the treatment. Notably, attendance in the individual intervention was slightly higher than for the group one. Overall, costs were lower in the group intervention and, while both interventions had significant weight loss in the first 16 weeks, only the group intervention continued to have significant weight loss after 24 weeks (Befort et al., 2010).

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Table 3. Behavioral Mail and Phone Interventions for Weight Management in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Sherwood et 1,801 over- Interventions: Weight Loss: PP: Interven- al. (2006) weight mem- 10 sequential I1: .73 (SE .22) tion bers (average interactive les- I2: .93 (SE .22) Weight-To-Be BMI 33.5) of sons with food C: .59 (SE .22) ACER (per 1- mail and managed care and exercise log (NS) kg lost): phone inter- organization. and feedback I1: $72.08 ventions for 72% female. from health d1: .026 I2: $132.70 weight loss in 600 in inter- counselor. d2: .063 C: $71.50 managed care vention #1, (1) Mail- Percent ≥5% settings 601 in inter- based: Mailed Weight Loss: vention #2, lesson, return I1: 13.33% 600 in control. for review, I2: 14.50% receive feed- C: 12.17% back and next (NS) lesson. Aver- age cost Percent ≥10% $50.45/ Weight Loss: participant. I1: 4.83% (2) Phone- I2: 5.33% based: All les- C: 4.33% sons mailed (NS) plus series of calls to pro- Despite treat- vide guidance ment availabil- (average ity over 24 length 19 months, partic- minutes). Av- ipation dimin- erage cost ished after 6 $127.39/ months. Partic- participant. ipation was a significant pre- Control: dictor of some Usual care. outcomes. Average cost $42.18/partici pant.

Measures: 24-month follow-up Befort et al. 34 rural wom- Interventions: Weight Loss PP: (2010) en (average Phone-based (kg): Healthcare BMI 34.4) in intervention Completers (I1 Group vs. in- U.S. 16 in in- guided by So- n=11, I2 n=16) Average Cost dividual tervention #1, cial Cognitive I1: 14.9 (4.4) per Successful

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness phone-based 18 in interven- Theory. Pre- I2: 9.5 (5.2) Participant obesity treat- tion #2. packaged meals, (p=.03) (≥10% Weight ment for rural instructions to d: 1.125 Loss): women increase physi- I1: $714.43 cal activity, diet Total I2: $1,029.06 and physical I1: 10.1 (8.2) activity logs, I2: 8.3 (6.0) and 16 weekly d: .254 then 4 biweekly sessions. Percent ≥10% (1) Group Weight Loss: treatment (16 I1: 62% women per I2: 50% group) for 60- minute ses- Decrease in sions. Pro- Daily Caloric gram costs Intake (kcal): $203.73/partic I1: 427 (321) ipant. I2: 542 (623) (2) Individual d: .244 treatment for 25-45-minute Increase in sessions. Pro- Physical Ac- gram costs tivity (METS): $382.26/partic I1: 747 (1149) ipant. I2: 508 (782) d: .248 Measures: 6 months

Telehealth Interventions: Internet Three studies assessed Internet-based weight loss programs, with only one compared to a traditional in-person program. A group behavioral weight loss intervention for persons who are overweight or obese was delivered either in-person or via the Internet. After six months, there was significantly higher weight loss in the in-person group than the Internet group, but the in-person group also cost more at $88.31 per kilogram lost compared to $67.74 for the Internet group. However, the incremental cost for the in-person version was only $7,177 more per life year, which was within standard willingness to pay thresholds (Krukow- ski et al., 2011; Harvey-Berino et al., 2010).

An Internet-based cognitive behavioral weight management program for non- active military personnel/retirees and their dependents who are overweight or obese had three levels of intensity: 1) written materials and a basic website, 2) added an interactive website with personalized feedback, and 3) added biweekly Motivational Interviewing (MI)-based coaching support alternating between 15-

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20 minute phone calls and personalized emails. There were no significant weight differences between the three after 15 to 18 months, but the most intensive option (including MI-based coaching support) cost $200 per additional percent weight loss and $4,400 to 5,600 per additional QALY, the latter within standard willingness to pay thresholds. No comparisons were made to in-person interventions or usual care. It is worth noting that less than 50% of participants in any intervention used the website or completed the weekly assignments, and less than 30% of participants completed the study follow-up (Hershey et al., 2012).

In a similar vein, an Internet-based weight management program was tested in active duty Air Force personnel. This intervention, most similar to the second one above, included a behavioral therapy component, weekly assignments, interactive readings, and personalized feedback. After six months, there were no significant differences between the intervention and usual care in terms of weight or BMI, but there was a higher percentage with at least 5% change in weight (22.6% vs. 6.8%). Overall, the incremental cost was $25.92 for each additional kilogram lost, $28.96 for each additional centimeter of waist circumference lost, and only $3.12 for each additional person with at least 5% change in weight. Cost-effectiveness will depend on the willingness to pay threshold for these metrics (Rasu et al., 2010; Hunter et al., 2008).

Table 4. Behavioral Internet Interventions for Weight Management in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Hershey et al. 486 over- Interventions: Percent PP: (2012) weight non- (1) Written Weight Loss: Healthcare active materials and I1: 4.1% Cognitive- TRICARE basic website. I2: 3.9% ICER (per behavioral beneficiaries Approx. cost I3: 5.3% QALY): weight man- (age 18-64 $2007145/partic I3 vs. I1/I2 agement pro- years; BMI 25- ipant. 35% Weight (in $20074,400 to gram 50); military used website, kg): 5,600 (Healthy Eat- person- 44% complet- I1: 95.9 (18.6) ing and Ac- nel/retirees ed measures. I2: 96.9 (19.1) ICER (per Life tive Living in and their de- (2) 1 plus in- I3: 95.0 (19.5) Year): TRICARE pendents). teractive web- (NS) I3 vs. I1/I2

Households) 74% women. site with tai- $20074,200 to 29% of origi- lored feed- d (I1 vs. 5,300 nal sample. back. Approx. I2): .053

155 in inter- cost $2007160/ d (I1 vs. I3): ICER (per 1- vention #1, participant. .047 percent 163 in inter- 38% used d (I2 vs. I3): weight loss): vention #2, website, 45% .098 I3 vs. I1/I2

168 in inter- completed $2007200 vention #3. measures. No significant (3) 2 plus brief difference in ACER (per Motivational weight-related QALY):

Interviewing- outcomes. I1: $2007900

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness

based coach- I2: $20071,100 ing support I3: $20071,900 every 2 weeks alternating ACER (per between Life Year):

phone and e- I1: $2007900 mail. Approx. I2: $20071,000 cost $2007390/ I3: $20071,800 participant. 46% used ACER (per 1- website, 49% percent completed weight loss):

measures, I1: $200730 53% complet- I2: $200740 ed >20% I3: $200770 coaching.

Measures: 15-18-month follow-up Krukowski et 318 over- Interventions: Percent PP: al. (2011) & weight (BMI Group behav- Weight Loss: Healthcare Harvey- 25-50) partici- ioral weight I1: 8.3% (6.1) Berino et al. pants recruit- loss program I2: 5.8% (5.4) ICER (per Life (2010) ed from gen- (12-18 people Year): eral popula- per group) for d: .435 $7,177 In-person vs. tion. 93% 24 weekly 60- Internet-based women. 157 in minute ses- Weight Loss ACER (per group behav- intervention sions. (kg): Life Year): ioral weight #1, 161 in in- (1) In-person I1: 8.0 (6.1) I1: $3,306 loss interven- tervention #2. program. Cost I2: 5.5 (5.6) I2: $2,160 tion $706/person. (p<.01) (2) Internet- ICER (per 1- based pro- d: .427 kg lost): gram with I1: $88.31 synchronous BMI (kg/sq. I2: $67.74 virtual inter- m): active “chat” I1: 33.19 sessions. Cost I2: 33.66 $373/ person.

Measure: 6 months Rasu et al. 446 active Intervention: Weight (in PP: (2010) & members (age Internet-based kg): Healthcare Hunter et al. 18-65 years; behavioral I: 85.5 (15.8)

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness (2008) BMI>25) of therapy, in- C: 87.4 (14.7) ICER (per 1- U.S. Air Force. cluding in- kg lost): Internet-based 227 in interperson orien- d: .125 $25.92 weight man- vention, 224 tation, weekly agement pro- control. interactive Waist Circum- ICER (per 1- gram in active readings, dai- ference (in addition cen- duty Air ly food and cm): timeter of Force person- physical activ- I: 92.2 (11.6) waist circum- nel ity diaries, C: 93.4 (12.8) ference lost): and weekly $28.96 individual- d: .098 ICER (per 1- ized feedback additional for 24 weeks. BMI: ≥5% weight Total cost I: 28.8 (3.3) change): $49.24/ C: 29.4 (3.0) $3.12 participant. d: .222 Control: Usual care. Percent ≥5% Weight Measures: Change: 6 months I: 22.6% C: 6.8%

Telehealth Interventions: Television Lastly, one intervention for overweight adults compared a videotaped in-person weight loss group to another set of individuals who watched the videotaped group on their television at home. This was also compared to an in-person group that was not videotaped (to control for any effects due to videotaping) and to a waitlist control. While all three interventions demonstrated weight loss over the waiting list in the first three months, only the television-delivered and non- videotaped in-person interventions maintained these differences after 15 months; it is not clear why the videotaped in-person intervention group did not. No cost- effectiveness analyses were conducted, but it was concluded that the television- delivered intervention was significantly more cost-effective than the two in- person ones. Meanwhile, despite the differences in weight loss between the two in-person treatments (videotaped or not videotaped), there were no significant differences in cost-effectiveness (Meyer et al., 1996).

Table 5. Behavioral Television Interventions for Weight Management in Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Meyer et al. 71 overweight Interventions: Body Weight PP: Interven- (1996) adults (age 20- (1) Video- at Pre and tion 58 years). taped live- then Post- Television- 90.9% female. contact Treatment Based on

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness delivered 57 in treat- weight loss (kg): weight loss out- weight loss ment, 15 in group for 8 I1: Pre: 82.06 comes, televi- intervention control. Only weekly 1-hour (17.87); Post: sion-delivered 34 completed sessions. 77.93 (13.90) group was sig- both 3-month (2) Television- I2: 88.77 nificantly more and 15-month delivered (10.66); 84.55 cost-effective assessments. weight loss (10.02) than both live group that ob- contact groups. I3: 86.55 served vide- Moreover, there otaped weight (15.69); 82.06 were no signifi- loss sessions (15.65) cant differences at home. C: 91.72 between the live (3) Non- (23.27); 90.86 contact groups videotaped (23.63) despite the non- live contact videotaped one weight loss Percent being more group that Overweight at clinically effec- was not vide- Pre and then tive. otaped for 8 Post- weekly 1-hour Treatment: sessions. I1: 36.5% (22.2); 29.8% Control: (23.3) Waiting list. I2: 42.4% (17.0); 35.6% Measures: (16.8) 15-month fol- I3: 44.2% low-up (25.4); 36.8% (25.4) C: 40.0% (24.4); 38.9% (25.8)

Older Adults Only one cost-effectiveness study specifically focused on improving diet, physical activity, and cancer screening for older adults, looking both at the general population and survivors of colorectal cancer. The telehealth interventions included either tailored printed newsletters provided in months 1, 3, 5, and 9, brief telephone-based Motivational Interviewing provided in months 2, 4, 6 and 9, or a combination of both the newsletters and phone calls compared to a control of generic cancer information. After one year, there were no significant changes in physical activity, weight, or BMI, so cost-effectiveness calculations focused on changes in fruit and vegetable consumption. However, this still led to very similar incremental costs per increase in fruit and vegetable intake between $106.81 and $128.17 (Campbell et al., 2009), suggesting all three interventions may be

302 Weight Management equally cost-effective to each other but would benefit from comparison to usual care or no intervention.

Table 6. Behavioral Interventions for Weight Management in Older Adults Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Campbell et 725 older Interventions: Fruit and PP: Interven- al. (2009) adults (age 40- (1) Mailed Vegetable tion 79 years). 181 computer- Daily Con- North Caroli- in interven- tailored news- sumption: ICER (per in- na Strategies tion #1, 185 in letters at 1, 3, General popula- cremental infor Improving intervention 5, 9 months. tion crease in daily Diet, Exercise, #2, 181 in in- (2) Brief 20- I1: 5.8 (2.1) fruit and veg- and Screening tervention #3, minute tele- I2: 6.0 (2.7) etable serv- (NC 188 in control. phone-based I3: 6.4 (2.8) ings): STRIDES) in For subset of Motivational C: 5.8 (2.4) I3 vs. I1 cancer survi- colorectal Interviewing $106.81 vors and gen- cancer (CRC) at 2, 4, 6, 9 CRC survivors I3 vs. I2 eral popula- survivors, 70 months. I1: 6.3 (3.0) $111.56 tion in interven- (3) Combined I2: 5.9 (2.8) I3 vs. C tion #1, 72 in intervention I3: 6.0 (3.2) $113.52 intervention of I1 and I2. C: 5.8 (2.9) I2 vs. C #2, 58 in in- Control: $115.15 tervention #3, Mailed gener- Weight (kg): I1 vs. C 66 in control. ic (non- I1: 177.6 (37.2) $128.17 For noncolo- tailored) I2: 183.1 (38.1) rectal cancer- printed health I3: 183.0 (53.8) Insufficient da- affected indi- information C: 179.2 (35.9) ta to calculate viduals, 111 in with cancer- ICER for CRC intervention related topics. BMI: survivors alone. #1, 113 in in- I1: 28.7 (5.4) tervention #2, Measures: I2: 29.2 (5.3) 123 in inter- 1 year I3: 29.3 (7.3) vention #3, C: 28.9 (5.1) 122 in control.

LIMITATIONS AND FUTURE DIRECTIONS Obesity is a complex health issue that can significantly impact not only morbidity and mortality but also psychological wellbeing and quality of life. Moreover, weight management can have significant health benefits beyond weight.

At a broad level, it is evident that behavioral management programs incorporating healthy eating, physical activity, and behavior skills training hold the promise of cost-effectiveness. Generally, trials with cost-effectiveness components focus on interventions designed to deliver care efficiently, which suggests a bias toward interventions that have a stronger likelihood of being cost-effective. For instance, studies above reveal the ways in which delivery, duration, and intensity impact overall cost-effectiveness. More data regarding the costs of interven-

303 Weight Management tions that were designed with a focus on clinical effectiveness and not cost- efficiency is needed. . Further, studies comparing in-person and telehealth interventions will provide additional data about potential cost-savings, and comparisons against usual care and no care will better inform the healthcare decision- maker. While the core components are similar, additional comparisons of duration and intensity will help hone in on the best balance of cost and efficacy. Fea- sibility and acceptability will also play a role, especially for difficult-to-reach populations like rural communities, as well as for sustaining the behavior changes after the intervention ends.

Changing health habits around diet and physical activity is hard, and willingness to change is an important factor in considering overall cost-effectiveness. Most studies of weight management programs rely on persons interested in participating; despite this, multiple studies above demonstrated low participation rates. Interventions that directly target willingness to change may increase overall cost- effectiveness, in part simply by increasing overall participation.

While any change in dietary practice and physical activity to promote healthy weight within a reasonable cost-effectiveness range seems beneficial, it is also important to define clinically meaningful change. While many behavioral interventions do demonstrate significant weight change in terms of kilograms lost, it would be valuable to know if this shifts classifications of overweight or obese in- to healthy ranges. Moreover, it does not appear that any national standards have been set for cost-effectiveness metrics around weight management yet.

Most studies tend to focus on populations that are already overweight or obese or that have sedentary lifestyles. While these populations will clearly benefit from weight management, preventive or early interventions that develop these healthy habits before unhealthy levels are reached are also likely to have long- term benefits. This is most evident in the need for early interventions with children and adolescents. The data indicate that childhood obesity is a clear risk factor for adulthood obesity; given this, focusing on building these health habits at a younger age will have significant cost benefits throughout the lifetime.

On the other end, many people who are already overweight or obese have significant co-occurring medical conditions. As we will discuss further, these lifestyle interventions can also have beneficial effects on Metabolic Syndrome disorders (see Chapter 13), and targeting and/or measuring additional health outcomes will help to better estimate and demonstrate overall cost-effectiveness. For instance, recommendations for diabetes management commonly include similar recommendations around caloric intake, physical activity, and behavior therapy. Given the high co-occurrence of obesity and type 2 diabetes, current analyses may be conservative in terms of cost-effectiveness of these interventions.

Finally, given the difficulty around practicing these health habits and the strong possibility for relapse, cost-effectiveness of studies for longer durations remains a critical gap in the literature. It would be helpful to know if people continue to engage in the healthy behaviors after the intervention and study end. After all, the longer participants maintain healthy weight, the greater the health benefits

304 Weight Management and the overall cost-effectiveness. However, if the effects disappear immediately afterward, then the cost-effectiveness findings will remain suspect.

The current data suggest overweight and obesity rates for both children and adults are starting to stabilize after years of being on the rise. However, it will be important to continue to monitor for any increasing patterns in these overweight and obesity rates, which would directly increase the overall economic burden. With current findings, we have data to support cost-effective solutions to maintain the stable rate, and hopefully to reverse the trend for this national epidemic.

KEY POINTS Children and Parents • For children and their parents, family-based treatment for both diet and physical activity was more cost-effective in group-only sessions (parents and children separate) than mixed group and individual sessions, with similar clinical outcomes for both children and parents and less costs after 12 months. More- over, family-based treatment delivered in joint treatment groups for parents and children dominated separate groups for parents and children with better clinical outcomes for both children and parents and less costs after 12 months.

Adults: In-Person Interventions • For healthy but sedentary adults, behavioral skills training to increase physical activity was less expensive and equally clinically effective as structured exercise training for physical activity, cardiorespiratory fitness, and blood pressure after two years, suggesting it would be more cost-effective per participant per month.

• For couples who have recently begun living together in Australia, an intervention to prevent sedentary behaviors focused on diet, physical activity, and healthy lifestyle appeared to be more cost-effective as a high-intensity intervention than a low-intensity one.

• For low-income women who are overweight or obese, a weight management program focused on healthy eating and physical activity with weekly group sessions was more cost-effective than a waiting list control after 16 weeks.

Adults: Telehealth Interventions • A telehealth intervention with interactive lessons and support from a health counselor for overweight and obese individuals found the mail-based version and usual care were equally cost-effective and twice as cost-effective as the telephone-based version in terms of the incremental cost per additional kilogram lost after two years.

• A telephone intervention for rural women found the group-based version dominated the individual-based version as more effective and less expensive after 24 weeks for those participants who completed the treatment.

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• An Internet-based group weight management program for persons who are overweight or obese was less cost-effective than the in-person group intervention after six months. The in-person intervention improved life years, well within standard willingness to pay thresholds.

• An Internet-based cognitive weight management program for non-active military personnel/retirees and their dependents who are overweight or obese was similarly effective across three different intensities after 15 to 18 months, with the most intensive option that included biweekly Motivational Inter- viewing-based coaching well within standard willingness to pay thresholds for QALY.

• An Internet-based weight management program, including behavioral therapy and personalized feedback, for active duty Air Force personnel had the potential to be more cost-effective than usual care after six months.

• A videotaped version of a weight management group for overweight adults watched at home could be more cost-effective than attending the in-person weight loss group given the costs were less and it was similarly effective to the non-videotaped in-person group after 15 months.

Older Adults • For older adults, personalized printed newsletters, telephone-based Motiva- tional Interviewing, or the combination of both appeared to be similarly effective and expensive after a year, although they were not compared to usual care or no care.

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Dzator JA, Hendrie D, Burke V, Gianguilio N, Gillam HF, Beilin LJ, Houghton S. A randomized trial of interactive group sessions achieved greater improvements in nutrition and physical activity at a tiny increase in cost. J Clin Epidemiol. 2004 Jun;57(6):610-9.

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Epstein LH, Paluch RA, Wrotniak BH, Daniel TO, Kilanowski C, Wilfley D, Finkelstein E. Cost-effectiveness of family-based group treatment for child and parental obesity. Child Obes. 2014 Apr;10(2):114-21.

Goldfield GS, Epstein LH, Kilanowski CK, Paluch RA, Kogut-Bossler B. Cost- effectiveness of group and mixed family-based treatment for childhood obesity. Int J Obes Relat Metab Disord. 2001 Dec;25(12):1843-9.

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Harvey-Berino J, West D, Krukowski R, Prewitt E, VanBiervliet A, Ashikaga T, Skelly J. Internet delivered behavioral obesity treatment. Prev Med. 2010 Aug;51(2):123-8.

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Hlatky MA. Economic endpoints in clinical trials. Epidemiol Rev. 2002;24(1):80-4.

Hunter CM, Peterson AL, Alvarez LM, Poston WC, Brundige AR, Haddock CK, Van Brunt DL, Foreyt JP. Weight management using the internet a randomized controlled trial. Am J Prev Med. 2008 Feb;34(2):119-26.

Krukowski RA, Tilford JM, Harvey-Berino J, West DS. Comparing behavioral weight loss modalities: incremental cost-effectiveness of an internet-based versus an in-person condition. Obesity (Silver Spring). 2011 Aug;19(8):1629-35.

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308 Metabolic Syndrome

CHAPTER 13: LIFESTYLE INTERVENTIONS FOR METABOLIC SYNDROME DISORDERS

ABSTRACT Metabolic Syndrome refers to having at least three of five metabolic risk factors – high blood pressure, high levels of blood sugar, high levels of triglycerides (blood fat), low levels of high-density cholesterol, and high levels of abdominal fat – which increase risk for type 2 diabetes, stroke, cardiovascular disease, and some cancers.

Common lifestyle factors (e.g., obesity, inactivity, poor diet, stress, smoking) contribute both to risk and disease course, leading to the most expensive cluster of medical disorders in the United States. Around a third (34%) of the United States population has Metabolic Syndrome, 29.5% hypertension, and 7% diabetes. These rates are much higher in older adults (age 65 years and older), in which 70.8% have hypertension, 60.3% dyslipidemia (i.e. high levels of triglycerides and/or cholesterol), and 21.2% diabetes. Annual direct and indirect cost estimates were $403.1 billion for cardiovascular disease, $17.4 billion for cardiovascular risk factors, and $245 billion for diabetes. Given the rising prevalence of Metabolic Syndrome, due in part to the aging of the population and in part to increasing rates of obesity, these costs are expected to grow exponentially.

Structured multifactorial lifestyle interventions are designed to target multiple shared behavioral risk factors simultaneously for prevention, early intervention, and disease management. Interventions typically focus on behavioral modifications such as losing weight, increasing exercise, improving diet, quitting smoking, decreasing alcohol consumption, and managing stress. However, limited cost-effectiveness data currently exist. For veterans with hypertension, a nurse-administered patient education intervention had the potential to be more cost-effective than usual care for controlling blood pressure in some patients, depending on the willingness to pay threshold. For adults at risk for type 2 diabetes and cardiovascular disease, a lifestyle intervention focused on at least 7% reduction in body weight was more cost-effective than metformin medication and may be more cost-effective than placebo up to ten years later. For adults who screened positive for type 2 diabetes, an early lifestyle intervention was less cost- effective than usual care after one year and five years because it was not clinically effective. For adults with type 1 diabetes and persistent, suboptimal glycemic control, the combination of diabetes-specific Motivational Enhancement Therapy (MET) and Cognitive Behavioral Therapy (CBT) dominated MET alone and may be more cost-effective than usual care after a year depending on the metric used.

Finally, in the general population, a web-based computer-tailored lifestyle intervention was not cost-effective in terms of QALY but might be in terms of lifestyle factors, depending on the willingness to pay threshold. Given the key role that behaviors play in onset and progression of these metabolic risk factors, it is clear more cost-effectiveness data for behavioral interventions are urgently needed.

309 Metabolic Syndrome

BACKGROUND ON DISORDER Some of the costliest medical disorders in the United States, both in terms of expense and years of life, are diseases such as type 2 diabetes, hypertension, heart disease, and stroke. Not surprisingly, both risk and prevalence increase with age. A complex interplay of behavioral, genetic, and environmental factors contribute to the development and course of these diseases. However, common lifestyle factors also contribute substantially to risk and progression. Moreover, the frequent co-occurrence of these disorders significantly impacts patients’ disease trajectories.

Lifestyle factors—also known as modifiable health risk behaviors—include being overweight or obese, inactivity or sedentary behavior, excessive or poor diet, chronic stress, smoking, and excessive alcohol consumption. Most behavioral interventions target improving some combination of these factors, such as exercise, changes in diet, decreases in substance use, and stress management, often with the goal of improving multiple health outcomes simultaneously. Given this practice, we have included these metabolic risk factors and metabolic disorders together.

These modifiable health risk behaviors increase the likelihood of metabolic risk factors including hypertension (high blood pressure), high levels of blood glucose (blood sugar), high levels of triglycerides (blood fat), low levels of high- density cholesterol (HDL), and high levels of stored body fat around the waist (e.g., “apple shaped” rather than “pear shaped” body). In turn, these metabolic risk factors increase the likelihood of metabolic-related conditions including type 2 diabetes and cardiovascular disease (e.g., heart disease, stroke). Type 2 diabetes is also a risk factor for cardiovascular disease.

Significantly, the greater the number of metabolic risk factors, the greater the risk for these metabolic-related conditions. Metabolic Syndrome refers to a clinical presentation with at least three of these five metabolic risk factors; this threshold is helpful for understanding increased risk for metabolic-related conditions such as type 2 diabetes, stroke, cardiovascular disease, and some cancers.

Importantly, since most metabolic-related conditions do not produce obvious symptoms until they have been unmanaged for years, they can go undetected for a long time. Even when these conditions are detected, treatment and adherence can be sub-optimal. Poor management of metabolic-related conditions due to delayed detection or ineffective intervention increases negative outcomes and associated costs. This supports the need for multifactorial lifestyle interventions focused on prevention, addressing subthreshold symptoms, detecting conditions early, and supporting on-going healthy lifestyle and treatment adherence.

PREVALENCE OF DISORDER For Metabolic Syndrome, prevalence in the United States was estimated around 34% or 68 million people as of 2006, which indicates a persistent increase from around 64 million people in 2000 and 50 million people in 1990. While some of these changes could be explained by increased detection, some are also due to increased abdominal obesity and high blood pressure, especially in younger

310 Metabolic Syndrome women (Mozumdar & Liguori, 2011). As of 1996, 10.2% of the U.S. population had hypertension, 3.6% had diabetes, and 1.3% had ischemic heart disease. Notably, these disorders often co-occur, particularly diabetes and ischemic heart disease (Druss et al., 2001).

It is imperative to note the higher prevalence rates in older adults (age 65 years and over), of which 70.8% have hypertension, 60.3% have dyslipidemia (i.e. high levels of triglycerides and/or cholesterol), and 21.2% have diabetes as of 2004 (McDonald et al., 2009). Prevalence is on the rise due to multiple factors including the aging of the population and increasing rates of obesity. Mortality is high for some of the metabolic-related conditions: Heart disease is the leading cause of death and stroke follows close behind as the third most common in the United States. Combined, heart disease and stroke were responsible for more than one-third of the deaths in the United States in 2003 (Mensah & Brown, 2007).

Hypertension and Cardiovascular Disease A more recent prevalence estimate for hypertension was 29.5% in 2010, and including pre-hypertension (i.e. elevated blood pressure that does not meet criteria for hypertension) increased estimates to 52.6%. Of those with hypertension, only 74.0% knew their hypertensive status, with lower levels of control (i.e. hypertension maintained within acceptable ranges) in men (40.3%) than women (56.3%). Lastly, prevalence is higher in older adults (over age 60 years) at around 60% (Guo et al. 2012).

Diabetes A more recent prevalence estimate for diabetes was 7%, increasing to 32.8% in older adults (age 65 years and older) as of 2012 (American Diabetes Association, 2013). It is estimated that a fourth of the population has pre-diabetes (i.e. elevated blood glucose levels that do not meet criteria for diabetes; Zhang et al., 2009a). Of those who do have diabetes, it is estimated that approximately a fourth (6.3 million people) do not know their diabetic status (Zhang et al., 2009b).

ECONOMIC BURDEN OF DISORDER In the United States, the combined economic burden of metabolic-related conditions is the highest of all health-related conditions. Notably, these estimates do not fully capture the additional health care costs for other health complications that results from these primary conditions (e.g., secondary infections).

Hypertension and Cardiovascular Disease Cardiovascular disease is the most expensive disease in the United States, with an annual economic burden from direct healthcare costs and indirect lost productivity costs estimated at $403.1 billion as of 2006. Of this, $258.5 million was due to heart disease, $142.5 billion to coronary heart disease, $57.9 billion to stroke, $63.5 billion to hypertension, and $29.6 billion to heart failure. These high costs are unsurprising given high prevalence and high mortality. Cardiovascular disease is also a leading cause of outpatient visits, emergency department visits, short-term hospitalizations, and expensive diagnostic and therapeutic procedures (Mensah & Brown, 2007).

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Further, the annual economic burden for some cardiometabolic risk factors (diabetes, hypertension, hyperlipidemia, overweight/obesity) was estimated at $79.8 million in direct healthcare costs and $17.3 billion in lost productivity as of 2005 (Sullivan et al., 2007a; Sullivan et al., 2007b). For both cardiovascular disease and cardiometabolic risk factors, data indicate excess body weight and obesity significantly worsen overall economic burden (Sullivan et al., 2008; Wang et al., 2002).

Diabetes For diabetes, annual economic burden was estimated at $245 billion as of 2012, with $176 billion (72%) from direct healthcare costs and $69 billion (28%) from indirect lost productivity costs. Interestingly, 59% of direct costs were driven by older adults (65 years and older) and 88% of indirect costs were driven by adults (under 65 years). On average, the healthcare costs of a person with diabetes are 2.3 times higher than for a person without diabetes (American Diabetes Association, 2013). It is further estimated that undiagnosed diabetes cost more than $18 billion as of 2007, with $11 billion due to direct costs and $7 billion due to indirect costs, and prediabetes cost more than $25 billion in healthcare costs as of 2007, with the majority of costs ($21 billion) due to medical conditions not directly linked to diabetes (Zhang et al., 2009a; Zhang et al., 2009b).

Lifestyle Factors The potential economic benefits of behavioral interventions to address lifestyle factors that contribute to metabolic-related conditions should not be undervalued. One study estimated that a healthier diet could save at least $70.9 billion annually in medical costs (47%), lost productivity (13%), and premature deaths (39%) due to improvements in Metabolic Syndrome disorders influenced by diet such as coronary heart disease, cancer, stroke, and diabetes (Frazão, 1999).

PROJECTED PREVALENCE AND ECONOMIC BURDEN OF DISORDER Critically, all prevalence rates and corresponding economic burden are projected to increase significantly in the next 15 to 35 years.

Hypertension and Cardiovascular Disease By 2030, 40.5% of the U.S. population is projected to have some form of cardiovascular disease, tripling direct medical costs from $273 billion in 2010 to $818 billion and increasing indirect costs by 61% from $172 billion to $276 billion (Heidenreich et al., 2011). Similarly, more than 8 million people (3%) are projected to have heart failure, increasing total annual costs to $70 billion, and 3.88% are projected to have stroke, increasing total annual costs by 129% to $240.67 billion (Heidenreich et al., 2013; Ovbiagele et al., 2013).

Diabetes Prevalence of diagnosed diabetes is estimated to double between 2010 and 2050, with approximately 20% to 33% of adults with diabetes by 2050 (Boyle et al., 2010; Narayan et al., 2006). While these researchers note that a formal projection of the associated costs is beyond the scope of their analysis, it is evident that any increase in prevalence will have a corresponding increase in costs.

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CLINICALLY EFFECTIVE INTERVENTIONS One of the main treatment goals for persons with metabolic risk factors is to delay or prevent the progression into metabolic disorders (especially type 2 diabetes) and to decrease risk for cardiovascular disease. Thus, treatment recommendations encourage interventions both for those with metabolic disorders as well as those at high risk for them.

Treatment recommendations focus on lifestyle modifications, primarily improving diet and increasing physical activity. Among other benefits, these modifications are intended to promote healthy weight loss, which contributes to risk reduction. Other target health behaviors include smoking cessation, reducing excessive alcohol consumption, and addressing psychological factors such as stress management. Note that behavioral interventions in the chapters on Alcohol Use (Chapter 8), Smoking (Chapter 9), and Healthy Weight (Chapter 12), while not designed specifically to target Metabolic Syndrome, may also be relevant. Structured multifactorial lifestyle interventions are specifically designed to modify multiple behaviors (e.g., diet, activity) that contribute to risk using tools and support such as education, tailored feedback, more frequent contact with providers, and individual and group sessions. There is wide variety in the elements that compose such interventions as well as in their intensity and duration.

A review of multifactorial lifestyle interventions for primary and secondary prevention of type 2 diabetes and cardiovascular disease concluded that individual studies have demonstrated efficacy in changing behaviors, improving quality of life, and impacting health outcomes such as incidence of diabetes or cardiovascular events, but that overall evidence for clinical efficacy remains unclear. The researchers note that variation in the observed clinical efficacy of multifactorial lifestyle interventions may be due in part to programmatic differences such as level of adherence, level of personalized tailoring, and any medication usage in the intervention or the comparison control (Angermayr et al., 2010). A review specific to those with or at high risk for cardiovascular disease concluded that lifestyle interventions (excluding medication use) were effective at improving habits (e.g., diet, physical activity) and risk factors (e.g., body weight, blood pressure) and at reducing incidence of diabetes and risk of cardiovascular disease (Blokstra et al., 2012). Lastly, a review specific to those with type 2 diabetes also concluded lifestyle interventions were beneficial (Chen et al., 2015).

While psychotherapy tools such as Motivational Interviewing or cognitive restructuring may be incorporated into the lifestyle interventions to support behavior modifications, these are not considered a primary treatment on their own. However, one study below investigated two psychological strategies: 1) Motivational Enhancement Therapy, a version of Motivational Interviewing designed to help individuals identify their ambivalence, generate internal motivations, set goals, and promote behavior change, and 2) Cognitive Behavioral Therapy to help individuals identify and overcome negative thoughts and behaviors related to their desired lifestyle changes around diet, exercise, substance use, and stress.

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Finally, pharmacotherapy may also be recommended to manage risk factors, especially to return levels to within normal ranges. These include diuretics or angiotensin-converting-enzyme (ACE) inhibitors for high blood pressure; statins, nicotinic acid and fibrates for cholesterol and triglyceride management; insulin or metformin for glycemic management; and aspirin for cardiovascular prevention; amongst others.

COST-EFFECTIVENESS OF LIFESTYLE INTERVENTIONS A review of interventions to increase physical activity concluded they improved survival (i.e. decrease disease incidence or progression) and health-related quality of life and were more cost-effective than no intervention in terms of life years or QALYs (range from $14,000 to $69,000 per QALY). This demonstrates the value of the physical activity component of lifestyle interventions (Roux et al., 2008).

Our review identified one study for a unique universal telehealth lifestyle intervention available to all adults in the Netherlands. The remainder of identified studies focused specifically on adults who already met criteria for at least one metabolic risk factor (e.g., hypertension, diabetes). In this universal intervention study, the option to participate was offered to all members of 2 provinces who choose to complete a major public health survey online. All participants received personalized risk appraisals for key lifestyle factors. The web-based computer-tailored multi-session lifestyle intervention was designed to motivate physical activity, increase fruit and vegetable intake, decrease alcohol consumption, and quit smoking, with two different delivery formats. In the sequential version, participants selected one target behavior in the first year and a second in the next year. In the simultaneous version, all target behaviors were included in both years. While the sequential version dominated the simultaneous one in terms of quality of life, both were in turn dominated by a minimal intervention. However, cost-effectiveness in terms of lifestyle factors depended on willingness to pay thresholds; at no value, the minimal intervention had the highest likelihood of being cost-effective, but at a value of €18,000, the simultaneous version has the highest likelihood of being cost-effective (Schulz et al., 2014).

Hypertension and Cardiovascular Disease For hypertensive veterans—the most common chronic condition in the Veteran Affair’s healthcare system—a nurse-administered telehealth behavioral intervention of bimonthly phone calls for patient education and problem-solving as well as tailored feedback designed to improve blood pressure control might be more cost-effective than usual care after two years. Cost-effectiveness estimates were right around standard willingness to pay thresholds per QALY for some populations but not others ($42,457 for normal weight women, $58,560 for overweight women, $87,300 for normal weight men, $43,567 for overweight men). This suggests higher likelihood of cost-effectiveness for normal weight women and overweight men, and not necessarily for overweight women or normal weight men (Datta et al., 2010; Boswell et al., 2009).

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Diabetes Three studies focused on diabetes, two with multifactorial lifestyle interventions for people at risk for or recently diagnosed with diabetes and one with psychotherapy for patients with persistent, suboptimal control of their diabetes.

A large-scale study of over 3,000 patients with high BMI and impaired glucose tolerance—risk factors for type 2 diabetes and cardiovascular disease—found an intensive lifestyle intervention focused on diet and physical activity of moderate intensity with a goal to achieve and maintain a reduction of at least 7% body weight dominated medication (metformin) in terms of both QALYs and additional cases of diabetes delayed or prevented after three years. However, whether the lifestyle intervention was more cost-effective than placebo depended on willingness to pay thresholds, costing $51,600 per QALY and $24,400 per additional case of diabetes delayed or prevented (Diabetes Prevention Program Research Group, 2003). A follow-up study after ten years offered the lifestyle intervention to all participants in addition to continuing their originally randomized intervention and revealed long-term cost-effectiveness of both the lifestyle and metformin interventions. The lifestyle intervention cost $14,365 per QALY relative to placebo, within standard willingness to pay thresholds. Cost- effectiveness estimates assuming group session-based delivery of the lifestyle intervention with similar outcomes found the lifestyle intervention only cost $1,681 per QALY. Metformin, supplemented with the lifestyle intervention, was now cost-saving relative to placebo, supplemented with the lifestyle intervention (Diabetes Prevention Program Research Group, 2012).

A study from the United Kingdom focused on early intervention for persons screened for type 2 diabetes and newly diagnosed for their previously undetected condition. All patients received routine diabetes care. Those in the early intervention also received an intensive multifactorial treatment with emphasis on more frequent provider-patient contact, additional education and feedback, and encouragement to lose weight, increase physical activity, avoid excessive alcohol consumption, stop smoking, take medications regularly, monitor blood glucose levels, meet with a dietician, and attend annual health checks. After both one year and five years, there were no significant gains in the intervention compared to routine diabetes care, including incidence of first cardiovascular event, which suggested the intervention was dominated by usual care (Tao et al., 2015).

Lastly, another study from the United Kingdom focused on adults with type 1 diabetes and more than two years of persistent, suboptimal glycemic control. Note that this is different than other metabolic disorders; type 1 diabetes typically has onset in childhood and is rooted in the body’s inability to produce sufficient insulin rather than changes in insulin resistance due in part to modifiable health risk behaviors; but behavioral strategies to promote glycemic control can be applicable across contexts. Diabetes-specific Motivational Enhancement Therapy (MET) with or without Cognitive Behavioral Therapy (CBT) was not significantly different from usual care in terms of QALYs after a year. However, there was significant improvement from combined MET and

CBT over either MET alone or usual care on a blood glucose measure (HBA1c),

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costing £1,756 per incremental improvement in HBA1c. Thus, cost-effectiveness will be dependent on the measure (QALY versus HBA1c) and the willingness to pay threshold for the latter (Patel et al., 2011). Given the short study duration, it is possible that the quality of life improvements may not be realized until later in life.

Table 1. Multifactorial Lifestyle Interventions for Metabolic Syndrome Disorders Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Schulz et al. 1,733 adults Intervention: Lifestyle PP: Societal (2014) (age 18-65 Web-based Factors (LSF): years) in the computer- I1: 3.38 ICER (per Universal Netherlands. tailored multi- I2: 3.42 QALY): Web-based 522 in session lifestyle C: 3.34 I1: Dominated tailored intervention intervention to I2: Dominated lifestyle #1, 517 in motivate I1 vs. I2: intervention intervention physical Dominant for adults #2, 664 in activity, control. increase fruit ICER (per and vegetable incremental intake, improvement in decrease LSF): alcohol I1: €4,594 consumption, I2: €10,850 and quit I1 vs. I2: €17,106 smoking. (1) Sequential Willingness to version pay threshold: targeting one If no value per lifestyle QALY, 49% behavior in probability first year and minimal one behavior intervention in second more cost- year. effective, 39% (2) Simultan- probability eous version sequential targeting all intervention, unhealthy 12% probability behaviors in simultaneous both years. intervention. At all values, Control: minimal Minimal intervention intervention. most likely to be cost-effective. Measures: If no value per 2 years gain in lifestyle

316 Metabolic Syndrome

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness factors, 48% probability minimal intervention more cost- effective, 42% probability sequential intervention, 10% probability spontaneous intervention. If value is €18K, 45% probability spontaneous intervention most cost- effective, 39% probability sequential intervention. Hypertension & Cardiovascular Disease Datta et al. 588 Intervention: % Blood PP: Healthcare (2010) & hypertensive Nurse- Pressure Bosworth et veterans in a administered Control: ICER (per Life al. (2009) primary care patient I: 54.4% Year): clinic. 294 in education C: 43.9% Normal weight intervention, behavioral women 294 in control. intervention (NS) $42,457 82% with bi- completed. monthly calls Overweight and tailored % Blood women information Pressure $58,560 designed to Improved: improve I: 14.3% Normal weight blood press- C: 5.6% men ure control $87,300 for 2 years. Mean cost Overweight men $112/year. $43,567

Control: Usual care.

Measures: 2-year

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Diabetes Tao et al. 1,024 persons Intervention: Incidence of PP: Healthcare (2015) with screen- Early First detected type multifactorial Cardiovascul ICER (per Multifactoria 2 diabetes (i.e. treatment ar Event: QALY): l treatment newly with more I: 7.2% After 1 year for patients diagnosed) frequent pro- C: 8.5% Dominated with type 2 across 69 vider-patient diabetes practices in contact; edu- No significant After 5 years (ADDITION- UK. 513 in cation and health gains at Dominated UK) intervention, feedback 1 year or 5 511 in control. sessions; en- years. couragement to lose weight, increase physical activity, avoid excessive alcohol intake, stop smoking, take medications regularly, self-monitor glucose levels, meet with dietician, and attend annual health checks. £981/person /5 years.

Control: Routine diabetes care.

Measures: 1 year & 5 years

Patel et al. 216 adults Interventions: HBA1c PP: Healthcare (2011) (age 18-65 (1) Diabetes- improvement and Social years) with specific : Services Motivational type 1 Motivational I1: .24 (1.46) Enhancemen diabetes and Enhancement I2: .59 (1.38) ICER (per 1-

318 Metabolic Syndrome

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness t Therapy ≥2 years Therapy for 4 C: .12 (1.17) point with and persistent, sessions over improvement in without suboptimal 2 months. d1: .091 HBA1c): Cognitive glycemic Average cost d2: .369 I2: £1,756 Behavior control in UK. £195/person. d3 (I1 vs. Therapy for 73 in (2) 1 plus I2): .246 Willingness to type 1 intervention Cognitive pay threshold: diabetes #1, 73 in Behavior At value of intervention Therapy for 8 £25K/QALY, #2, 70 in sessions over only 33% control. an additional probability for 4 months. either Average cost intervention to £660/person. be more cost- effective than Control: usual care. Usual care. Only calculated Measures: ICER when 1 year significant differences in both costs and outcomes, not when neutral or dominant. Diabetes 3,234 patients Intervention: Percent PP: Societal Prevention (BMI≥24) with (1) Intensive Reduced Program impaired lifestyle Incidence of ICER (per Research glucose intervention Type 2 QALY): Group (2003 tolerance, a with 16 Diabetes: 2.8 3 years & 2012) risk factor for weekly years I1: $51,600 type 2 lessons then I1: 58% I2: $99,200 Lifestyle diabetes and monthly I2: 31% intervention cardiovascular sessions with 10 years versus disease. goal to Direct I1: $14,365 metformin achieve/main Medical I2: Cost-saving for At the end of tain a weight Costs I1 vs. I2: $42,753 prevention year 3, all reduction of (excluding I1 if delivered of type 2 participants ≥7% body interventions) via group diabetes were weight : format with encouraged to through diet 10 years same outcome: continue the and physical I1: $24,563 $1,681 intervention to activity of I2: $25,615 which they moderate C: $27,468 ICER (per case were intensity. of diabetes randomized, Approx. cost delayed or

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness and all $2,300/partici prevented): participants pant/3 years, 3 years were offered and I1: $24,400 the intensive estimated at I2: $34,500 lifestyle $4,600/partici intervention. pant for the After 3 years, the Of the original 10 years, lifestyle sample, 2,766 assuming intervention continued, 910 treatment dominated from I1, 924 was delivered metformin from I2, and as group medication, but 932 from sessions. its cost- Control. Those (2)Medication effectiveness initially (metformin) relative to placebo randomized to with 1 will depend on the the lifestyle dose/day, willingness to pay intervention increased to 2 thresholds. were offered 2 doses/day additional after 1 month. booster Adherence sessions per reinforced via year during quarterly 10-year visits. follow-up. Approx. cost $2,200/ participant/3 years, and $2,300/partici pant for the 10 years. Control: Placebo. Cost was approx. $770 at 10 years from participation in lifestyle intervention.

Measures: 3 & 10 years

LIMITATIONS AND FUTURE DIRECTIONS It is widely understood that much more needs to be done to decrease the skyrocketing healthcare costs associated with these metabolic conditions. While it seems evident that behavioral modifications to improve lifestyle risk factors

320 Metabolic Syndrome should be the recommended course of action, the data do not yet unequivocally support their cost-effectiveness. A better understanding of which components of these structured multifactorial lifestyle interventions may be more or less clinically- and cost-effective will help inform future results.

Additionally, studies for longer duration may be able to demonstrate more substantial clinical benefits and cost savings that are not apparent in the shorter term, especially given the potential cost-savings of preventing or delaying these metabolic conditions. While these interventions may incur more costs during their implementation, the longer-term benefits may not be appreciated until ten to twenty years later. This may also impact willingness to pay thresholds, which would benefit from more standardization. While general recommendations are to utilize the standard measure of a QALY for ease of comparison, in this case, the improvements to quality of life may not be perceived during the early course of these disorders, when most studies assess effects. Moreover, as with decreasing alcohol use or ceasing to smoke, the initial behavior changes may even be considered difficult or unpleasant, temporarily decreasing perceived quality of life before improving it significantly. Effective interventions may prevent a future drop in quality of life rather than improve quality of life. Cost- effectiveness measures based on the prevention or delay or these disorders may be more relevant for the intended outcomes of improving overall health.

More data on interventions focused on prevention, early detection, and early treatment are also needed. Building lifestyle habits early by targeting children and adolescents before they reach risk thresholds will likely have long-term benefits but would require longitudinal data throughout the lifetime. Targeting adults between the ages of 18 and 65 may also lead to additional benefits, since prevalence is vastly higher after the age of 65 and continues to increase with age. Studies to ascertain the cost-effectiveness of early detection, including for those at high risk (i.e. exhibiting subthreshold levels of key factors), may find it to be more cost-effective than when those factors have already reached more difficult to manage levels.

Interventions for older adults may need to be better tailored to the specific needs and limitations of this population. A potential issue that warrants further study is poor adherence. Some of the data imply adherence may be a key factor in why these interventions do not consistently demonstrate clinical- or cost-effectiveness. Clearly, making behavioral changes at any age is hard. Making these changes without feeling a palpable change (e.g., decrease in blood pressure) may make motivation especially difficult. Making these changes within the constraints of older age (e.g., limited mobility) may require additional guidance. In short, a better understanding of the barriers to fully engaging in the multifactorial lifestyle interventions may inform changes to maximize success in the future.

KEY POINTS • For Metabolic Syndrome risk factors and disorders, multifactorial lifestyle interventions intended to target multiple health behaviors are one of the most

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commonly tested behavioral approaches for prevention, early intervention, and disease management.

• For adults in general, a web-based computer-tailored multi-session lifestyle intervention designed to increase positive health behaviors either sequentially or simultaneously was dominated by minimal intervention in terms of QALY after two years, but may be cost-effective in terms of lifestyle factors. For improving lifestyle factors, the sequential format dominated the simultaneous one.

• For veterans with hypertension, a nurse-administered telehealth behavioral intervention may be more cost-effective than usual care after two years for normal weight women and overweight men, but exceeds standard willingness to pay thresholds for overweight women and normal weight men.

• For adults with impaired glucose tolerance, a lifestyle intervention focused on reducing at least 7% body weight through diet and physical activity dominated metformin medication in terms of both QALYs and reduced incidence of diabetes after three years. Starting after the 3 year assessment, the lifestyle intervention was provided to all adults in addition to their originally randomized intervention. At 10 years, metformin combined with the delayed lifestyle intervention was now cost-saving over placebo plus the delayed lifestyle intervention, and the original lifestyle intervention alone cost $14,365 per QALY over placebo with the delayed lifestyle intervention.

• For adults screened and newly diagnosed for type 2 diabetes, an intensive intervention focused on more contact, feedback, education, and encouragement for health behaviors was dominated by routine diabetes care after both one year and five years as more expensive without any significant differences in health outcomes.

• For adults with type 1 diabetes and more than two years of persistent, suboptimal glycemic control, the combination of diabetes-specific Motivational Enhancement Therapy (MET) and Cognitive Behavioral Therapy (CBT) dominated MET alone and may be more cost-effective than

usual care per incremental improvement in HBA1c after a year. While neither MET alone or plus CBT were more cost-effective than usual care in terms of QALY, quality of life improvements may not be as apparent in the short-term.

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Sullivan PW, Ghushchyan V, Wyatt HR, Wu EQ, Hill JO. (2007b). Productivity costs associated with cardiometabolic risk factor clusters in the United States. Value Health. 2007 Nov-Dec;10(6):443-50.

Tao L, Wilson EC, Wareham NJ, Sandbaek A, Rutten GE, Lauritzen T, Khunti K, Davies MJ, Borch-Johnsen K, Griffin SJ, Simmons RK. Cost-effectiveness of intensive multifactorial treatment compared with routine care for individuals with screen-detected type 2 diabetes: analysis of the ADDITION-UK cluster- randomized controlled trial. Diabet Med. 2015 Feb 6.

Wang G, Zheng ZJ, Heath G, Macera C, Pratt M, Buchner D. Economic burden of cardiovascular disease associated with excess body weight in U.S. adults. Am J Prev Med. 2002 Jul;23(1):1-6.

Zhang Y, Dall TM, Chen Y, Baldwin A, Yang W, Mann S, Moore V, Le Nestour E, Quick WW. (2009a). Medical cost associated with prediabetes. Popul Health Manag. 2009 Jun;12(3):157-63.

Zhang Y, Dall TM, Mann SE, Chen Y, Martin J, Moore V, Baldwin A, Reidel VA, Quick WW. (2009b). The economic costs of undiagnosed diabetes. Popul Health Manag. 2009 Apr;12(2):95-101.

325 Sleep Disorders

CHAPTER 14: SLEEP DISORDERS

ABSTRACT Sleep disorders, or regular disruptions in sleeping patterns that impair daytime functioning and increase health and societal risks, have numerous clinical presentations (e.g., from sleep-related breathing disorders like sleep apnea to sleep-related movement disorders like periodic limb movement). Unfortunately, sleep disorders are significantly underrecognized, underdiagnosed, and undertreated. In this review, we focus on the most common sleep disorder, insomnia, as the only one with relevant cost-effectiveness data.

Insomnia is defined by persistent difficulty with sleep onset, sleep maintenance, and/or feeling unrefreshed after sleep, which can cause excessive daytime sleepiness and negatively impact energy levels, cognitive abilities, and emotional states. Insomnia can occur on its own or as an outcome of other neuropsychiatric and medical disorders, including other sleep disorders. It is estimated that 6% to 40% of the U.S. population has experienced insomnia symptoms, with multiple estimates around 20%. Meanwhile, the annual economic burden of insomnia is estimated to range from $30 to $100 billion.

Cognitive Behavioral Therapy for Insomnia (CBT-I) has proven to be clinically effective across multiple populations including patients with primary insomnia, patients with insomnia comorbid with other conditions, older adults, and chronic users of hypnotic medications. Despite this, little cost-effectiveness data exist. Two studies of group-based CBT-I for adults with chronic sleep problems suggest the potential for cost-effectiveness in specific populations. The first targeted adults in primary care who were long-term users of hypnotic medications, and found group CBT-I was highly cost-effective over no intervention. The second was limited to patients who self-referred to community services, and found brief CBT-I of a one-day workshop and one follow-up session was not cost-effective over a waiting list in terms of QALYs but may be in terms of sleep quality, depending on the willingness to pay threshold; however, it was not compared to standard CBT-I. Another avenue to improve cost- effectiveness could be clinically effective innovative healthcare delivery systems (e.g., telehealth, stepped care), but more data are needed.

BACKGROUND ON DISORDER Sleep disorders encompass a large class of disorders related to the disruption of typical sleeping patterns. While it is not uncommon to experience occasional or short-term trouble with sleeping, major health concerns arise when these sleep issues become recurrent or chronic and interfere with normal daytime functioning. Given the breadth of sleep disorders, this chapter will focus primarily on the most common disorder—insomnia—for which the most data are available.

Insomnia includes persistent difficulty with falling asleep, staying asleep (e.g., waking during the night or too early in the morning) and/or feeling unrefreshed after sleep, despite the time and resources to do so. The official diagnostic criteria of the Diagnostic and Statistical Manual (DSM-5) specifies that these sleep

326 Sleep Disorders difficulties occur at least three times a week and persist for at least three months, while the International Statistical Classification of Diseases (ICD-10) specifies that they must also include daytime distress or impairment. Insomnia can be acute or chronic, situational, recurrent, or persistent, and can occur by itself (primary insomnia) or as a result of another disorder (comorbid insomnia), including other sleep disorders. Unsurprisingly, this constant lack of rest can cause excessive daytime sleepiness and impact energy levels, cognitive abilities (e.g., difficulties remembering, attending, focusing), mood (e.g., depression, anxiety, irritability), and other physical symptoms (e.g., headaches, stomach aches).

After insomnia, the most common sleeping disorders center on breathing and movement. Sleep-related breathing disorders range from snoring to sleep apnea (periodic pauses in breathing while sleeping). The most common form, obstructive sleep apnea, occurs when muscles in the back of the throat relax. Understandably, these pauses in breathing are not good for health and can contribute to difficulties staying asleep, abrupt awakenings, and excessive daytime sleepiness. Meanwhile, sleep-related movement disorders range from teeth grinding and jaw clenching (sleep bruxism) to periodic limb movements (often legs, as in restless legs syndrome). Other sleep disorders include narcolepsy, hypersomnia, parasomnia, and circadian rhythm disorders (e.g., shift work). For more details, Thorpy (2012) reviews the major classifications for sleep disorders.

As mentioned, insomnia can occur as a stand-alone disorder or as an outcome of other disorders. For instance, insomnia has demonstrated a bi-directional relationship with anxiety and depression and has been associated with medical conditions such as hypertension, cardiovascular disease, diabetes mellitus, gastrointestinal disorders, and chronic pain. Insomnia can also lead to adverse outcomes such as increases in alcohol abuse (e.g., used as an informal sleep aid; Skaer & Sclar, 2012). Significantly, sleep disorders and subsequent daytime sleepiness can have consequences beyond the individual’s personal health. These include impairments in productivity or workplace absenteeism and increases in both work-related and non-work-related injuries and accidents (e.g., car collisions).

Given all of this, one of the most notable aspects of sleep disorders is how often they go unrecognized, undiagnosed, and untreated. When insomnia is not considered seriously or only considered a symptom and not a disorder on its own, it may not be diagnosed or treated properly. On the other hand, despite the similar symptomology to insomnia across these various contributors, different causes may benefit from different types of treatment.

PREVALENCE OF DISORDER Estimates for the prevalence of sleep disorders in the United States vary, but consistently show higher prevalence in women than men and increasing prevalence with age. For adults, some estimate that 25% are dissatisfied with their sleep, while others estimate that 35% to 40% have trouble falling asleep or experience daytime sleepiness. Meanwhile, up to half of older adults (age 65

327 Sleep Disorders years and older) experience difficulty with initiating or maintaining sleep and more than half experience chronic disruption of sleep (Hossain & Shapiro, 2002; Botteman, 2009; Crowley, 2011; McCall, 2004).

Estimates for the prevalence of insomnia in the United States range from 6% to 40%, with multiple estimates around 20% (50 to 60 million people). In older adults, prevalence of insomnia was estimated at 20% to 29% in one report but may be as high as 40%. Notably, the American Insomnia Survey assessed more than 10,000 people with insurance and found that the two most widely used diagnostic criteria (DSM-4, ICD-10) led to vastly different prevalence estimates of 3.9% to 22.1%. One reason might be that ICD’s criteria require that the patient is preoccupied with or has excessive concern about sleeplessness and its consequences; many patients with sleeping problems do not experience excessive concern or preoccupation with sleeplessness. (Martin et al., 2004; McCall, 2004; Crowley, 2011; Roth et al., 2011).

Depending on the diagnostic criteria, estimates for the prevalence of obstructive sleep apnea could range from 2-4% or 4-9.1%. Significantly, it is estimated that 80-90% of people with obstructive sleep apnea go undiagnosed. Unlike some sleep disorders, obstructive sleep apnea is more common in men than women (Hossain & Shapiro, 2002; Morin & Benca, 2012; Botteman, 2009).

ECONOMIC BURDEN OF DISORDER No recent or comprehensive estimates of the economic burden of sleep disorders in the United States are currently available, and most researchers note the need for more robust data. In 1990, it was estimated that the annual direct costs of sleep disorders were $15.9 billion, likely constrained by current under diagnosis and treatment. In 1988, it was estimated that the annual indirect costs of sleep- related accidents (due generally to drowsiness) was $43 to $56 billion (Hossain & Shapiro, 2002). In 2004, it was estimated that the annual indirect costs of sleep- related workplace injuries exceeded $100 billion, using a conservative prevalence estimate for sleep disorders (Kessler et al., 2012).

For insomnia, the annual direct and indirect costs in the United States may exceed $100 billion. A conservative estimate was $30 to $35 billion as of 1994, based on prevalence around 10%. A much higher estimate of $92.5 to $107.5 billion for the same period, based on prevalence around 33%, has undergone scrutiny. It seems likely that the true estimate lies somewhere between the two. Meanwhile, other estimates include annual direct costs of $13.9 billion in 1995, annual indirect costs due to lost productivity of $41.1 billion in 1988, and annual indirect costs in the workplace from $15 to $92 billion (Chilcott & Shapiro, 1996; Hossain & Shapiro, 2002; Botteman, 2009; Léger & Bayon, 2010; Kessler et al., 2011).

No clear estimates exist for obstructive sleep apnea. Based on data of the economic burden in Australia ($7.5 billion in 2004), the burden in the United States might be estimated at roughly ten-times that cost (AlGhanim et al., 2007). In terms of healthcare resources, it is estimated that persons with undiagnosed obstructive sleep apnea cost twice as much as those without it, driven in part by

328 Sleep Disorders increased cardiovascular morbidity (Tarasiuk & Reuveni, 2013). Lastly, an estimate limited to the annual impact of car collisions (including fatalities) due to obstructive sleep apnea was $15.9 billion (Sassani et al., 2004). Given the substantial economic costs of obstructive sleep apnea, it is remarkable that clinical trials assessing cost-effectiveness of interventions are not yet available.

CLINICALLY EFFECTIVE INTERVENTIONS Behavioral interventions are first-line treatment for insomnia, including Relaxation Therapy, Stimulus Control Therapy, and Sleep Restriction Therapy. Relaxation Therapy focuses on reducing somatic tension (e.g., using autogenic training or progressive muscle relaxation) and reducing intrusive thoughts (e.g., using meditation or imagery training) that interfere with sleep. Stimulus Control Therapy focuses on developing a consistent sleep-wake cycle (e.g., what time the person sleeps and wakes) and strengthening the association between the bed with sleep (e.g., only use bed for sleep, leave bed when unable to sleep). Sleep Restriction Therapy also focuses on the sleep-wake cycle, but starts by limiting the time spent in bed, which results in mild sleep deprivation. The intention is to cause more consolidated sleep. Sleep duration is systematically increased until the optimal duration is achieved, but caution should be used during treatment to ensure that any daytime sleepiness that occurs does not lead to adverse outcomes.

Cognitive Behavioral Therapy for Insomnia (CBT-I), the most commonly recommended treatment option, generally includes a combination of the behavioral components above plus cognitive strategies to target excessive worries, misconceptions, and unreasonable expectations around sleep. In general, Cognitive Behavioral Therapy (CBT) targets both behaviors and cognitions that perpetuate the maladaptive state. Thus, CBT-I targets factors that perpetuate insomnia including psychological factors (worry, unrealistic expectations, unhelpful beliefs), behavioral factors (poor sleep habits, irregular sleep schedules), and physiological factors (mental and somatic tension, hyperarousal). CBT-I has demonstrated long-term benefits, including for adults with co- occurring neuropsychiatric or medical conditions, for chronic sedative-hypnotic medication users, and for older adults (Morin & Benca, 2012; Morin et al., 2006; Morgenthaler et al., 2006).

Pharmacotherapy may be recommended for short-term use in certain cases, although usually combined with behavioral interventions. While sedative- hypnotic medications (e.g., benzodiazepine receptor agonists) may provide short-term relief from sleep disorders, these effects do not last once use is discontinued and there are substantial concerns about long-term use, development of physical dependence or addiction, and increased risk of falls and other adverse events, particularly in the elderly and in patients taking other medications that could contribute to sedation. In theory, the combined approach allows for the more immediate effects of the medications as well as the more sustained effects of the behavioral interventions, although there are mixed findings regarding whether these combined effects are any better than behavioral interventions alone.

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COST-EFFECTIVENESS OF INTERVENTIONS A meta-analysis comparing the efficacy of psychotherapy and pharmacotherapy for acute insomnia found they both produce similar short-term outcomes. While the costs of medication are typically less than those for behavioral interventions, the reviewers note the need to consider the impact on indirect costs (e.g., work productivity) as well as the longer-term benefits of behavioral interventions that might offset the initial higher costs of treatment (Smith et al., 2002).

A comprehensive review found that no cost-effectiveness analyses of insomnia management had been completed through 2002. Looking at the sparse data for costs and effectiveness separately, the researchers concluded that insomnia was associated with high costs and poor health-related quality of life. They also noted that behavioral interventions, while more time-intensive than medication, appeared to have equal short-term effectiveness and better long-term outcomes (Martin et al., 2004). Since then, Botteman (2009) has identified one cost- effectiveness trial, and our review identified a second trial published in 2014. Given these limitations, we also summarize a few other findings that hint at the potential for cost-effectiveness for behavioral interventions, such as cognitive behavioral therapy for insomnia.

Both cost-effectiveness studies tested group Cognitive Behavioral Therapy for Insomnia (CBT-I) for sleeping problems in adults in the United Kingdom. The first relied on patients who self-referred to community-based services, and was delivered as a brief version with a one-day workshop and one six-week follow- up booster session. After three months, this brief intervention produced clear improvements in insomnia and depression symptoms but not in health-related quality of life. In other words, the intervention was not cost-effective in terms of QALYs but has the potential to be cost-effective in terms of sleep quality. At a willingness to pay threshold of £150 per incremental improvement on an insomnia measure (Insomnia Severity Index), the intervention had a 95% likelihood of being more cost-effective than no intervention (Bonin et al., 2014; Swift et al., 2012).

Meanwhile, group CBT-I delivered in primary care for six sessions was cost- effective for patients with chronic sleep difficulties and long-term sedative- hypnotic drug use, significantly improving sleep quality and reducing sedative- hypnotic drug use. After six months, 33% of persons in the intervention had not used any sedative-hypnotics compared to 8.1% without intervention, and over half (54.2%) had decreased their frequency of sedative-hypnotic use by more than half compared to 17.7% without intervention. Even though costs were significantly higher in the intervention, it only cost £3,418 per QALY, well within standard willingness to pay thresholds. Notably, the clinical improvements persisted at 12 months, indicating the likelihood for cost-effectiveness at longer time intervals as well (Morgan et al., 2004).

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Table 1. Behavioral Interventions for Sleep Disorders Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Bonin et al. 111 Intervention: Insomnia PP: Societal (2014) & participants Brief Severity Swift et al. who self- psychoeducat Index (ISI): ICER: (2012) referred for ional group I: 10.78 (5.95) Not provided treatment in Cognitive C: 16.19 (5.01) Community- UK. 49 in Behavioral Willingness to based intervention, Therapy for d: .987 pay threshold: Cognitive 62 in control. Insomnia At no value per Behavioral (CBT-I) via Beck QALY, 1% Therapy for community- Depression probability brief Insomnia based 1-day Inventory CBT-I more (CBT-I) workshop (BDI): cost-effective workshops and 6-week I: 10.73 (8.31) than waiting booster C: 15.27 list. At value of session. Costs (11.16) £30K, 34% approx. d: .466 probability £150/person. more cost- effective. At no Control: value per Waiting list incremental for 3 months. improvement in ISI, 6% probabil- Measures: ity brief CBT-I 3-month more cost- follow-up effective than waiting list. At value of £150, 95% probability more cost- effective. At no value per additional person in subclinical range of ISI, 6% probability brief CBT-I more cost-effective than waiting list. At value of £1.8K, 80% probability more cost- effective, and at value of £8K, 99% probability

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness more cost- effective. Morgan et al. 124 patients Intervention: Change in PP: Healthcare (2004) with chronic Group Pittsburgh and Social sleep Cognitive Sleep Quality Services Psychologica difficulties Behavioral Index (PSQI): l treatment and long-term Therapy I: 1.9 Total Costs: for insomnia sedative- ‘sleep clinic’ C: -1.4 I: £1999-2000272.4 in the hypnotic drug delivered by (p=.04) (SE 21.7) regulation of use (min. 1 trained non- C: £1999-2000142.6 long-term month, mean specialist Change in (SE 30.5) sedative- 13.4 years) primary care Frequency (p<.01) hypnotic across 23 counselors in of Hypnotic drug use general six 50-minute Drug Use ICER (per practices in sessions. Cost (number of QALY):

UK. 65 in £1999-2000154/ hypnotic-free £1999-20003,418 intervention, patient. nights per 59 in control. Control: week): No additional I: -2.4 treatment. C: -.2 (p<.001) Measures: 6-month Change in follow-up Mean Hypnotic Dose (as proportion of max. dose prescribed): I: -4.4% C: 1.4% (NS)

Clinical improvements maintained at 12-month follow-up.

Healthcare Delivery Systems As we discuss in the final section of this book, innovative healthcare delivery systems have the potential to increase any savings provided by clinically effective interventions. Given the limited cost-effectiveness data, we review how some of these systems have been applied to Cognitive Behavioral Therapy for Insomnia (CBT-I), a relatively established treatment option. Non-traditional delivery systems may work well for CBT-I because of this treatment’s strong

332 Sleep Disorders emphasis on development of self-management skills. As the clinical effect of CBT-I depends on the patients’ consistent use of skills that they have learned, time spent in contact with therapists may be less relevant insofar as alternative methods of skills training and encouragement to use skills are effective (Bastien et al., 2004).

Compared to in-person individual or group therapy, telehealth interventions are likely to incur lower costs and potentially achieve similar clinical outcomes. Thus far, CBT-I has been clinically effective for primary insomnia in adults when delivered in person, mailed as a self-help intervention, or delivered via the Internet (Trockel et al., 2011). Similarly, a meta-analysis found that both minimal contact (e.g., telephone support, brief appointments) and self-help (e.g., text-, audio-, video-, Internet-based) demonstrated small to moderate long-term clinical benefits in sleep efficiency, sleep quality, and sleep onset (van Straten & Cuijpers, 2009). Overall, data suggest both face-to-face and self-administered CBT-I programs are beneficial, although effects may be greater in in-person (Espie, 2009).

Espie (2009) pointed out the potential resource difficulties of scaling up traditional CBT-I and proposed a stepped care model to capitalize on the effectiveness of other delivery formats. In short, this entails initiating treatment with less intensive versions of the therapy and, if the patient does not respond, shifting them to more intensive versions. For insomnia, less intensive versions of CBT include self-help, minimal contact, or brief interventions, followed by manualized delivery by non-specialists (e.g., nurses, graduate students) in group or individual settings. In cases where patients do not respond to these formats, they can be referred to traditional individual face-to-face treatment with a trained specialist.

LIMITATIONS AND FUTURE DIRECTIONS First and foremost, better processes are needed to identify and diagnose sleep disorders, which too often go unrecognized and untreated. It is surprising to see the limited data available on the economic burden of sleeping disorders and cost- effective solutions, especially given their pervasiveness both alone and alongside other disorders, as well as the clear evidence of significant societal consequences (e.g., increased healthcare utilization, decreased productivity, increased accidents).

Given the established clinical efficacy of behavioral interventions for insomnia alongside reservations about long-term medication use, cost-effectiveness studies should naturally follow suit. However, one complicating factor may be the difficulty in diagnosing insomnia since it is based in part on subjective experience. In other words, two people could have similar sleep-wake patterns, but only one of them may express the cognitive, emotional, and/or physical symptoms that impede daytime functioning. A better understanding of the mechanisms behind difficulties with sleep onset and sleep maintenance as well as the perception of non-restorative sleep may provide a better understanding of how insomnia operates. On the other hand, the wide variety of causes linked

333 Sleep Disorders with insomnia may warrant different diagnostic and treatment methods, making it difficult to generalize and draw broad conclusions.

While we have presented some options to make Cognitive Behavioral Therapy for Insomnia (CBT-I) more accessible and affordable by delivering it in a group setting, in a brief format, via telehealth, or through self-management, cost- effectiveness analyses will need to confirm whether the benefits gained compensate for any costs saved. The limited data suggest that even without improvements in quality of life, improvements in sleep quality and depression symptoms can be achieved; thus, cost-effectiveness analyses will also need to decide on the most relevant metric. Moreover, studies of longer duration may reveal quality of life improvements that were not immediately apparent.

The complete absence of cost-effectiveness data for behavioral interventions for any other sleep disorder is significant. While some types of disorders may benefit more or less from behavioral interventions (e.g., established treatments for obstructive sleep apnea focus more on breathing mechanisms), it is evident that psychological factors play a key role in the stress, anxiety, and frustration that accompanies poor sleep. Thus, interventions that alleviate these symptoms will not only contribute to overall health and wellbeing but may also improve adherence to other types of treatment.

KEY POINTS • There is a lack of data on the cost-effectiveness of behavioral interventions for sleep disorders. The only two studies available are both for Cognitive Behavioral Therapy for Insomnia (CBT-I).

• For patients who self-referred to community services for sleep problems, a brief one-day CBT-I workshop and follow-up booster session were not cost- effective in terms of QALYs but may be in terms of sleep quality, with a 95% likelihood of being more cost-effective than no intervention at £150 per incremental improvement in the Insomnia Severity Index after three months.

• For patients with chronic sleep problems and long-term sedative-hypnotic use, group CBT-I in primary care was cost-effective at £3,418 per QALY over no intervention after six months. The clinical improvements persisted at 12 months, indicating the likelihood of cost-effectiveness at longer time intervals.

• Innovative healthcare delivery systems can reduce intervention costs, such as telehealth, non-specialist care, and stepped care models. These delivery formats have all demonstrated clinical efficacy for CBT-I and may increase the likelihood of cost-effectiveness; however, formal analyses are needed.

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Bonin EM, Beecham J, Swift N, Raikundalia S, Brown JS. Psycho-educational CBT-Insomnia workshops in the community. A cost-effectiveness analysis alongside a randomised controlled trial. Behav Res Ther. 2014 Apr;55:40-7.

Botteman M. Health economics of insomnia therapy: implications for policy. Sleep Med. 2009 Sep;10 Suppl 1:S22-5.

Chilcott LA, Shapiro CM. The socioeconomic impact of insomnia. An overview. Pharmacoeconomics. 1996;10 Suppl 1:1-14.

Crowley K. Sleep and sleep disorders in older adults. Neuropsychol Rev. 2011 Mar;21(1):41-53.

Espie CA. "Stepped care": a health technology solution for delivering cognitive behavioral therapy as a first line insomnia treatment. Sleep. 2009 Dec;32(12):1549- 58.

Hossain JL, Shapiro CM. The prevalence, cost implications, and management of sleep disorders: an overview. Sleep Breath. 2002 Jun;6(2):85-102.

Kessler RC, Berglund PA, Coulouvrat C, Fitzgerald T, Hajak G, Roth T, Shahly V, Shillington AC, Stephenson JJ, Walsh JK. Insomnia, comorbidity, and risk of injury among insured Americans: results from the America Insomnia Survey. Sleep. 2012 Jun 1;35(6):825-34.

Kessler RC, Berglund PA, Coulouvrat C, Hajak G, Roth T, Shahly V, Shillington AC, Stephenson JJ, Walsh JK. Insomnia and the performance of US workers: results from the America insomnia survey. Sleep. 2011 Sep 1;34(9):1161-71.

Léger D, Bayon V. Societal costs of insomnia. Sleep Med Rev. 2010 Dec;14(6):379- 89.

Martin SA, Aikens JE, Chervin RD. Toward cost-effectiveness analysis in the diagnosis and treatment of insomnia. Sleep Med Rev. 2004 Feb;8(1):63-72.

McCall WV. Sleep in the Elderly: Burden, Diagnosis, and Treatment. Prim Care Companion J Clin Psychiatry. 2004;6(1):9-20.

Morgan K, Dixon S, Mathers N, Thompson J, Tomeny M. Psychological treatment for insomnia in the regulation of long-term hypnotic drug use. Health Technol Assess. 2004 Feb 8(8):iii-iv, 1-68.

Morgenthaler T, Kramer M, Alessi C, Friedman L, Boehlecke B, Brown T, Coleman J, Kapur V, Lee-Chiong T, Owens J, Pancer J, Swick T; American Academy of Sleep Medicine. Practice parameters for the psychological and behavioral treatment of insomnia: an update. An american academy of sleep medicine report. Sleep. 2006 Nov;29(11):1415-9.

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Morin CM, Benca R. Chronic insomnia. Lancet. 2012 Mar 24;379(9821):1129-41.

Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA, Lichstein KL. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998-2004). Sleep. 2006 Nov;29(11):1398-414.

Roth T, Coulouvrat C, Hajak G, Lakoma MD, Sampson NA, Shahly V, Shillington AC, Stephenson JJ, Walsh JK, Kessler RC. Prevalence and perceived health associated with insomnia based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders, Second Edition criteria: results from the America Insomnia Survey. Biol Psychiatry. 2011 Mar 15;69(6):592-600.

Skaer TL, Sclar DA. Economic implications of sleep disorders. Pharmacoecon. 2010;28(11):1015-23.

Smith MT, Perlis ML, Park A, Smith MS, Pennington J, Giles DE, Buysse DJ. Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia. Am J Psychiatry. 2002 Jan;159(1):5-11.

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Trockel M, Manber R, Chang V, Thurston A, Taylor CB. An e-mail delivered CBT for sleep-health program for college students: effects on sleep quality and depression symptoms. J Clin Sleep Med. 2011 Jun 15;7(3):276-81. van Straten A, Cuijpers P. Self-help therapy for insomnia: a meta-analysis. Sleep Med Rev. 2009 Feb;13(1):61-71.

336 Somatic Symptoms

CHAPTER 15: CHRONIC SOMATIC SYMPTOMS

ABSTRACT Chronic somatic symptoms are recurrent physical symptoms such as pain, dizziness, fatigue, and bloating, among many others. Somatic Symptom Disorders occur when these symptoms cause distress or disrupt functioning. In these disorders, distress and functional impairment are in part due to excessive thoughts, feelings or behaviors about the symptoms.

Somatic Symptom Disorder sub-classifications include Chronic Fatigue Syn- drome (CFS) and Irritable Bowel Syndrome (IBS). CFS includes persistent fatigue along with other symptoms like pain and impaired cognitive abilities, all of which worsen after physical or mental exertion. IBS includes abdominal pain along with other exacerbated intestinal symptoms like constipation or diarrhea. The underlying causes are typically unknown, which has generated controversy and complicates diagnosis and treatment.

Prevalence estimates are rough: 5% to 7% for Somatic Symptom Disorders, 0.4% to 3.3% for CFS, and 10% to 15% for IBS. Similarly, estimates for annual economic burden are limited: $256 billion for healthcare costs due to somatization; $2 to $7 billion for healthcare costs and $9.1 billion for lost productivity due to CFS; and a potential range of $1.6 to $30 billion for direct and indirect costs due to IBS. Since underlying causes typically cannot be identified or treated, most interventions focus on psychosocial approaches to manage symptoms and improve functioning.

For Somatic Symptom Disorders, Mindfulness-Based Cognitive Therapy was less cost-effective than usual care, but Mindfulness Therapy and enhanced usual care, including psychiatric consultation and treatment planning, were equally cost- effective. Group Therapy appeared more cost-effective than enhanced usual care, including a physician consultation letter. A multicomponent collaborative stepped care program for high healthcare utilizers with medically unexplained symptoms improved mental health without increasing costs, suggesting cost- effectiveness. For CFS, Cognitive Behavioral Therapy (CBT) dominated guided support groups, and might be more cost-effective than no intervention depending on the willingness to pay threshold. CBT appeared to be equally cost- effective to non-directive counseling. CBT was more cost-effective than Graded Exercise Therapy at all willingness to pay thresholds; as before, it might be more cost-effective than no intervention depending on the willingness to pay threshold. For IBS, both psychotherapy and paroxetine (an antidepressant medication) improved quality of life and cost less than usual care, but the cost savings were only significant for psychotherapy. Adding CBT to mebeverine hydrochloride (an antispasmodic agent) had the potential to be more cost-effective than mebeverine hydrochloride alone during the first three months but was less cost-effective at later times. Internet-based CBT for patients attending a gastroenterological clinic or participants identified online was cost-saving over a waiting list or online forum at reducing IBS symptoms at the end of the intervention and for up to a year later.

337 Somatic Symptoms

Overall, the cost-effective potential of psychosocial interventions to improve function and reduce costs for chronic somatic symptoms is evident, but more data are needed.

BACKGROUND ON DISORDER Somatization refers to medically unexplained physical symptoms, which some hypothesize are the manifestation of psychological distress. Broadly, chronic somatic symptoms include physical symptoms like pain, headache, dizziness, fatigue, muscle weakness, bloating, diarrhea, and shortness of breath, among others. Symptoms may be relatively specific (e.g., back pain) or nonspecific (e.g., fatigue). These symptoms often have no discernable cause, but they can be caused by medical or neuropsychiatric conditions. In the latter case, the symptoms usually exceed expected norms for the frequency and/or intensity of the symptoms.

Importantly, symptom intensity can influence cognitions, feelings, and behaviors. In other words, positive behaviors that appear to immediately worsen chronic somatic symptoms such as work, exercise, social activities or other life activities might be decreased and negative behaviors that appear to improve the symptoms in the short-term such as inactivity and substance use might be increased, leading to habits that impair function and prevent recovery. These maladaptive responses to symptoms lead to decreased health and well-being and increased distress over the long-term, typically increasing the intensity and persistence of the somatic symptoms over time. Cognitive and behavioral interventions focus on improving reactions to symptoms, developing effective coping skills, and re- versing avoidance of healthful activities necessary for recovery, to break a vis- cous cycle of symptoms leading to responses that produce more symptoms in the future.

Somatic Symptom Disorder When one or more of these somatic symptoms persists for at least six months, causes significant distress, and results in substantial disruption in functioning, it is classified as Somatic Symptom Disorder (formerly known as Somatoform Dis- order and Somatization Disorder). The disorder usually includes excessive or disproportionate thoughts, feelings, and/or behaviors about the symptoms themselves.

Controversy exists around these classifications, mostly due to the lack of identifiable causes. Historically, diagnoses were limited to medically unexplainable symptoms. However, it is difficult to conclusively ascertain whether or not a given symptom has an explainable cause. This risks over-diagnosis of symptoms as medically unexplainable at the expense of identifying and treating underlying disorders. Currently, the focus has shifted to the person’s quality of life and whether they are suffering. The debate around diagnostic criteria will continue to evolve; this review summarizes available data relying on the former diagnostic criterion limited to medically unexplained symptoms.

Additionally, specific clusters of somatic symptoms have sub-classifications including Insomnia (see Chapter 14 on Sleep Disorders), Fibromyalgia (see Chapter 16 on Chronic Pain), Chronic Fatigue Syndrome (CFS), and Irritable Bowel Syn-

338 Somatic Symptoms drome (IBS). Note that these do not include Hypochondriasis (i.e. health anxiety), which entails concerns about health in the absence of somatic symptoms (see Chapter 1 on Anxiety Disorders).

Chronic Fatigue Syndrome (CFS) Fatigue (tiredness as opposed to sleepiness) is a common symptom across multiple illnesses and needs to be assessed carefully. Chronic Fatigue Syndrome (CFS) includes unexplained persistent fatigue for at least six months that is not alleviat- ed by rest or sleep and is easily exacerbated by exertion (e.g., extreme exhaustion lasting more than 24 hours after physical or mental exercise). Additional symptoms include impaired memory or concentration; unexplained muscle or joint pain; headaches not previously experienced; tender lymph nodes; and recurring sore throat. CFS can last for years and negatively impacts daily life functioning.

Currently, the cause of CFS remains unknown and there are no tests to diagnose it. Unlike the updated guidelines for Somatic Symptom Disorder, diagnosis is based primarily on ruling out other medical causes. CFS is classified as a syndrome as there might be multiple etiologies that lead to similar symptoms. Pos- sible causes include infections, immune dysfunction, stress, low blood pressure, nutritional deficiency, or some combination of factors, but research to date has not been able to find a direct connection between these factors and CFS.

Controversy around CFS includes its name, although some alternative names are considered distinct disorders by others. The most common is Myalgic Encepha- lomyelitis or Myalgic Encephalopathy (ME). The name means “muscle pain” (myalgia) and "inflammation of the brain and spinal cord" (encephalomyelitis), which some find misleading as cause has not yet been connected specifically to inflammation of the central nervous system. Others appreciate the implication of a breadth of symptoms beyond fatigue. A common compromise is the combined term “CFS/ME” or “ME/CFS” to avoid confusion.

This cluster of symptoms is also very similar to Fibromyalgia (see Chapter 16 on Chronic Pain), except with a focus on fatigue rather than pain. These two terms are sometimes used interchangeably, demonstrating the continuing lack of understanding for the underlying causes of these somatic conditions.

Irritable Bowel Syndrome (IBS) Somatic symptoms of Irritable Bowel Syndrome (IBS) focus on the colon (large intestine) including abdominal pain, cramping, bloating, diarrhea, constipation, and gas. These symptoms must be accompanied by a change in bowel function, lead to significant discomfort and distress, and persist with frequency for a significant amount of time (e.g., at least 3 days a month for the past 3 months).

Like CFS, IBS is a syndrome with a cluster of somatic symptoms of unknown cause that look similar to common symptoms for multiple illnesses. Thus, diagnosis is again based primarily on ruling out other possible medical causes. It is particularly important to distinguish IBS from Inflammatory Bowel Disorder (IBD), which has similar symptoms but is caused by Crohn’s disease or ulcerative colitis and has increased risk for colorectal cancer.

339 Somatic Symptoms

Hypotheses for external causes include after an infection, due to intestinal bacte- rial growth, or due to stress. Hypotheses for internal causes include poor communication between the brain and intestines, which may cause overreactions to the normal digestive process, and stronger or weaker intestinal contractions. This may impact how food moves through the gastrointestinal system. Stronger contractions could lead to gas, bloating and diarrhea, and weaker ones to constipation. Another possibility is a decrease in or less diversity in gut flora.

PREVALENCE OF SOMATIC SYMPTOM DISORDERS This limited understanding about these somatic disorders leads to limited data on prevalence and economic burden, and is quite possible existing prevalence data provide underestimates given the lack of standardization around diagnoses.

Somatic Symptom Disorders The prevalence of Somatic Symptom Disorder in the United States is not known, but is estimated to be between 5% and 7% and to be higher for women than men. This falls between estimates for the former classifications of Somatization Disor- der at 1% and undifferentiated Somatoform Disorder at 19% (American Psychiat- ric Association, 2013).

Chronic Fatigue Syndrome (CFS) No nationally representative data are available, with studies using regional data to extrapolate national estimates. Globally, recent meta-analyses of Chronic Fa- tigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) estimated prevalence between 0.4% and 3.3% (Johnston et al., 2013; Dinos et al., 2009).

Irritable Bowel Syndrome (IBS) Approximately 30 million people are estimated to meet diagnostic criteria for Ir- ritable Bowel Syndrome (IBS) in North America; prevalence estimates range from 3% to 20% with most in the 10% to 15% range (Saito et al., 2002). A large-scale study of more than 5,000 persons in the United States estimated prevalence at 14.1%, with 3.3% from official diagnoses and 10.8% from undiagnosed cases meeting criteria. In other words, more than three-quarters (76.6%) of people with IBS were undiagnosed (Hungin et al., 2005).

ECONOMIC BURDEN OF SOMATIC SYMPTOMS DISORDERS As with prevalence, limited data impact estimates of economic burden. Overall, a common concern for chronic somatic symptoms is patients who seek out multiple consultations and unnecessary tests in efforts to find a treatable cause. In fact, some physicians may even treat nonexistent diseases in part to alleviate such efforts, which can later lead to other harmful effects (e.g., medication addiction). Physicians tend not to treat the associated psychological distress, which contributes to mental and physical dysfunction including problems with interpersonal relationships and work performance (Luo et al., 2007). All of these diagnostic and treatment limitations can lead to increased costs, particularly due to higher healthcare utilization and increased work absenteeism, making Somatic Symp- tom Disorders some of the most expensive disorders (Fjorback et al., 2013a).

340 Somatic Symptoms

Somatic Symptom Disorders It is evident the debilitating and persistent effects of Somatic Symptom Disorders contribute significantly to economic burden, but no representative data are available for the United States. For somatization (i.e. medically unexplained somatic symptoms), regional data were extrapolated to estimate an annual economic burden of an additional $256 billion in total healthcare costs as of 2002, with overall healthcare costs for persons with somatization almost double those for persons without somatization (Barksy et al, 2005).

Chronic Fatigue Syndrome (CFS) For Chronic Fatigue Syndrome (CFS), the annual national economic burden was extrapolated from regional data to approximately $2 to $7 billion in direct healthcare costs ($2,342 to $8,675 per person with CFS) and $9.1 billion in lost productivity costs ($20,000 per person with CFS; Jason et al., 2008; Reynolds et al., 2004). Similar estimates for annual costs from the state of Georgia were $11,780 per person with CFS, $8,544 from lost productivity and $3,286 from direct medical costs. Notably, this totaled almost double the medical costs for persons without CFS (Lin et al., 2011).

Irritable Bowel Syndrome (IBS) For Irritable Bowel Syndrome (IBS), estimates for economic burden vary widely depending on included costs and estimated prevalence. Patients with IBS visit the doctor more frequently, use more diagnostic tests, consume more medications, are hospitalized more frequently, miss more workdays, and have lower work productivity. These costs are even higher for those with more severe symptoms and lower quality of life (Spiegel et al., 2009). Across three reviews, estimates for annual direct costs ranged from $530 to $8,750 per person with IBS, with one study estimating annual indirect costs at $355 to $3,344 per person (In- adomi et al., 2003; Canavan et al., 2014; Maxion-Bergemann et al., 2006).

Inadomi et al (2003) estimated the annual economic burden at $1.56 billion, with $1.35 billion from direct costs and $205 million from indirect costs. This is much lower than prior estimates of $8 billion in direct costs in 1995 to $26.4 billion in direct and indirect costs in 1998. However, some believe these higher estimates were inflated due to a significant overestimate in prevalence (Camilleri & Wil- liams, 2000). Others assert the direct and indirect costs of IBS are greater than $20 to $30 billion annually (Spiegel et al., 2009; Cash, 2005).

CLINICALLY EFFECTIVE INTERVENTIONS Unfortunately, effective treatments do not always exist or are not provided for Somatic Symptom Disorders (Fjorback et al., 2013a). In most cases, the first step is to investigate and eliminate potential underlying causes for the symptoms. Subsequently, behavioral interventions are recommended to target the maladaptive thoughts, emotions, and behavioral patterns that maintain the disorder and impair function and quality of life. Treatments rarely focus on the symptoms themselves, as the underlying physical causes are usually unknown. This is similar to recommendations for Chronic Pain (see Chapter 16).

341 Somatic Symptoms

Somatic Syndrome Disorder Treatment guidelines for the former classifications of Somatoform Disorder and Somatization Disorder include developing a strong physician-patient relationship to manage symptoms. This may require physician education, and Cognitive Behavioral Therapy for the patient. Pharmacotherapy is not currently recommended, but may be utilized for specific symptoms (e.g., pain) or co-occurring disorders.

Cognitive Behavioral Therapy (CBT) for chronic somatic symptoms teaches patients to focus less on the physical cause of the symptoms and more on the thoughts and behaviors that perpetuate the symptoms. Addressing the thoughts and behaviors that maintain the symptoms may both reduce the intensity and frequency of symptoms, and also decrease distress and help the patient function despite the symptoms. This can lead to a reduction in healthcare utilization as well.

Other psychosocial interventions reviewed here include Mindfulness Therapy, Group Therapy, and a multicomponent stepped care program. Mindfulness Therapy includes noticing and accepting thoughts and feelings as they occur without attaching meaning to them or reacting to them. Mindfulness-Based CBT combines awareness of thoughts and feelings with modifying the thoughts and behaviors that contribute to negative experiences. Group Therapy is offered to a set of people with similar symptoms, and multicomponent stepped care programs provide a series of sequential treatments added incrementally only if the preceding one is ineffective at alleviating distress.

Chronic Fatigue Syndrome (CFS) Currently, there are no clearly effective treatments for CFS. Given this, recommendations again focus on the physician-patient relationship to manage symptoms and Cognitive Behavioral Therapy (CBT), although evidence is less promising for CBT in CFS. As before, pharmacotherapy is not recommended in general but may be provided for specific symptoms, such as sedatives for unrefreshing sleep or stimulants for cognitive function, among others.

CBT for CFS often incorporates Graded Exercise Therapy, which promotes a gradual increase in frequency and intensity of physical activity. Since one of the most common features of CFS is a worsening of symptoms after any exertion, it is hoped that pacing physical activity to stay within an optimal zone may help prevent this worsening of symptoms and thus continue to encourage rather than discourage physical activity.

Irritable Bowel Syndrome (IBS) Most dietary and pharmaceutical recommendations for IBS have limited evidence, including dietary modifications (e.g., eliminating specific foods), supple- ments (e.g., probiotics), anti-spasmodic medication (e.g., mebeverine), and anti- diarrheal medication (loperamide). However, antidepressants (e.g., tricyclic antidepressants and selective serotonin reuptake inhibitors) are effective in relieving the physical symptoms of IBS, and prosecretory agents (linaclotide and lubipro- stone) are effective in constipation-predominant IBS.

342 Somatic Symptoms

Psychotherapy is effective for IBS. Evidence supports Cognitive Behavioral Ther- apy (CBT), Hypnotherapy, Multicomponent Psychological Therapy, and Dynam- ic Psychotherapy, but cost-effectiveness data are only available for generic psychotherapy and CBT at this time. As before, CBT for IBS focuses more on the thoughts and behaviors that perpetuate the symptoms than the cause that precip- itated them.

COST-EFFECTIVENESS OF INTERVENTIONS

Somatic Symptom Disorders Available studies for Somatic Symptom Disorder use the former diagnoses of Somatoform Disorder and Somatization Disorder and are limited to medically unexplained symptoms, with only one calculating cost-effectiveness and the remainder providing separate data on clinical efficacy and associated costs.

Two studies assessed Mindfulness Therapy. In the Netherlands, group-based Mindfulness-Based Cognitive Therapy for undifferentiated Somatoform Disorder was less cost-effective than usual care (including psychiatric interview) at €56,637 per QALY after nine months. This is outside standard willingness to pay thresholds. However, at a higher willingness to pay threshold of €80,000 per QALY, Mindfulness-Based Cognitive Therapy had a 57% likelihood of being more cost- effective (van Ravesteijn et al., 2013). In Denmark, group-based Mindfulness Therapy for Bodily Distress Syndrome (including Somatization Disorder, Fi- bromyalgia, and Chronic Fatigue Disorder) appeared to be equally cost-effective as enhanced usual care (including options for psychiatric consultation and treatment plan). While significantly fewer people in the Mindfulness Therapy received disability pension (25% versus 45%), there were no other clinical differences. Since both treatments were equally effective at decreasing healthcare costs after 15 months, it is possible they both may be more cost-effective than non- enhanced usual care, but this would need to be formally assessed in future studies. Notably although there were no significant differences in overall costs, psychiatric services cost significantly less in Mindfulness Therapy than enhanced usual care (Fjorback et al., 2013a; Fjorback et al., 2013b).

Group Therapy for Somatization Disorder significantly improved physical and mental functioning and reduced healthcare costs over enhanced usual care (including physician consultation letter with treatment recommendations) after a year, suggesting cost-effectiveness. Interestingly, only 45% of participants assigned to Group Therapy completed even one session; thus, it appears that simply being invited to join appeared to have positive effects with no significant differences between those who completed the therapy and those who did not (although there was a pattern of greater improvements the more sessions attended; Kashner et al., 1995).

Lastly, for patients in primary care with at least two years of high healthcare utilization and at least six months of medically unexplained symptoms, a multicomponent intervention including a collaborative stepped care approach, Cogni- tive Behavioral Therapy, medication management, and promotion of positive physician-patient relationships offered for one year appeared more cost-effective

343 Somatic Symptoms than usual care after two years. The multicomponent intervention had significant clinical improvements (49.0% versus 33.3%) without any additional healthcare costs, suggesting cost-effectiveness (Luo et al., 2007; Smith et al., 2006).

Table 1. Behavioral Interventions for Somatic Symptom Disorders Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness van 96 primary Intervention: General PP: Societal Ravesteijn et care patients Mindfulness- Health Status al. (2013) with undiffer- Based Cogni- (VAS): ICER (per entiated So- tive Therapy I: 63.5 (18.3) QALY):

Mindfulness- matoform for eight 2.5- C: 66.7 (16.9) €201056,637 Based Cogni- Disorder in hour group tive Therapy the Nether- sessions and d: .182 Willingness to for Somato- lands. 55 in instructions pay threshold: form Disor- intervention, for 45-minute SF-36 Mental If no value per der 41 in control. daily practice Component QALY, 28% at home. Av- Summary probability erage (MCS): Mindfulness- cost €450/pe I: 39.6 (12.1) Based Cognitive rson. C: 42.7 (10.2) Therapy more cost-effective Control: d: .278 than usual care. Usual care If value is €40K, plus psychi- SF-36 Physi- 48% probability atric inter- cal Compo- cost-effective, view. nent Sum- and if value is mary (PCS): €80K, 57% prob- Measures: I: 47.0 (12.3) ability cost- 9-month fol- C: 46.3 (10.5) effective. low-up d: .061 Fjorback et 119 patients Intervention: SF-36 Physi- PP: Healthcare al. (2013a & with Bodily Mindfulness cal Compo- 2013b) Distress Syn- Therapy with nent Sum- Mean Total drome (Soma- psychoeduca- mary (PCS): Costs:

Mindfulness tization Dis- tion and I: 34.0 (10.6) I: $20073,937 Therapy for order and so- Graded Exer- C: 35.3 (9.5) (6,117)

Bodily Dis- matic syn- cise Therapy C: $20073,355 tress Syn- dromes) for at for eight 3.5- d: .129 (5,488) drome (So- least two years hour weekly (NS) matization in Denmark. group (12 pa- Percent with Disorder, Fi- 100% Somati- tients) ses- Disability Mean Psychiat- bromyalgia, zation Disor- sions. Cost Pension: ric Services Chronic Fa- der, 80% Fi- $3,102/perso I: 25% Costs: tigue Syn- bromyalgia, n. C: 45% I: $20073,211 drome) 70% Chronic (p=.025) (2,407)

Fatigue Syn- Control: C: $2007744 (737)

344 Somatic Symptoms

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness drome. 59 in Enhanced No pension at (p<.0001) intervention, usual care baseline 60 in control. plus option of I: 20% psychiatric C: 38% consultation (p=.042) and treatment plan. Cost $564/ person.

Measures: 15-month follow-up Luo et al. 189 patients in Intervention: Percent Im- PP: Societal (2007) & primary care Multicompo- provement: Smith et al. with 2 years of nent collabo- I: 49.0% Total Costs: (2006) high health- rative C: 33.3% I: $6,659 (6,229) care utiliza- stepped care C: $7,928 Multicom- tion and at intervention Odds Ratio of (13,339) ponent least 6 months provided by Likelihood of (NS) intervention of unex- nurse practi- Improve- for medically plained symp- tioners in- ment: unexplained toms in a staff- cluding Cog- Treatment symptoms model HMO. nitive Behav- group 94 in interven- ioral Thera- 2.16 tion, 95 in con- py, medica- (p=.019) trol. tion management, and Mental health positive phy- 2.14 sician-patient (p<.001) relationship with twelve Physical func- 20-minute tion visits plus 0.56 periodic 5-10 (p=.003) minute phone calls over 1 Body pain year. 1.51 (p=.039) Control: Usual care.

Measures: 2 years Kashner et 70 patients Intervention: Positive scores PP: Healthcare al. (1995) with Somati- Short-term indicate im-

345 Somatic Symptoms

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness zation Disor- Group Ther- provement rel- Reduction in To- Group Ther- der. 84.3% fe- apy for 8 bi- ative to control tal Annual Costs apy for So- male. 44 in in- weekly 2- on 100-point (per person): matization tervention, 26 hour sessions scale. $513 (95% CI, 11 Disorder in control. (4-6 patients) to 824) to develop Improvement peer support, in Physical Previous studies share coping Functioning: indicate the con- methods, and 3.36 sultation letter increase emo- (p<.05) (included in both tional abili- the intervention ties over 4 Attended vs. and control) re- months. 45% not attended duced total costs attended 1 or 12.91 by $295, which more sessions could increase (average 2.2 Improvement cumulative sav- sessions). in General ings. Cost $832/ Health: intervention. 2.04

Control: Attended vs. Physicians not attended receive con- 29.38 sultation letter with Improvement treatment in Mental recommenda- Health: tions. 6.98 (p<.001) Measures: 1- year fol- Attended vs. low-up not attended 35.46

Improvement in Social Functioning: -1.37

Attended vs. not attended 22.61

346 Somatic Symptoms

Chronic Fatigue Syndrome (CFS) All three cost-effectiveness studies for Chronic Fatigue Syndrome (CFS) included Cognitive Behavioral Therapy (CBT), with two compared to generic counseling or support groups and one to Graded Exercise Therapy.

In the Netherlands, Cognitive Behavior Therapy (CBT) dominated guided support groups for patients with CFS after six months. However, compared to no intervention, CBT cost €21,375 per QALY and €20,532 per additional improved patient; the former might be considered within or near standard willingness to pay thresholds but the latter has no established threshold. In other words, CBT was more cost-effective than guided support groups and may or may not be more cost-effective than no intervention, depending on the metric used and the associated willingness to pay threshold (Severens et al., 2004).

In the United Kingdom, CBT and non-directive counseling may be equally cost- effective as both interventions improved fatigue and reduced overall costs for patients with CFS after six months. Although program costs were lower for non- directive counseling compared to CBT, the differences were not significant. Comparing the two options to usual care or no intervention would provide more data on overall cost-effectiveness (Chisholm et al., 2001; Risdale et al., 2001). Meanwhile, CBT may be the most clinically effective option for CFS patients after 8 months. It was more cost-effective than Graded Exercise Therapy per clinically significant decrease in fatigue (minimum four-point improvement) at all willingness to pay thresholds, and may be more cost-effective than usual care (including a self-help booklet), depending on the willingness to pay threshold. If no value were assigned to a clinically significant decrease in fatigue, there was only 23.7% likelihood that CBT was more cost-effective than usual care, but if it was valued at £4,500, then it increased to 81.8% likelihood (McCrone et al., 2004).

Table 2. Behavioral Interventions for Chronic Fatigue Syndrome (CFS) Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness McCrone et 130 partici- Interventions: Percent Clini- PP: Societal al. (2004) pants with (1) Cognitive cally Signifi- Chronic Fa- Behavioral cant Decrease Total Costs:

Cognitive tigue in UK. Therapy in- in Fatigue I1: £2000-011,970 Behavioral 52 in interven- cluding activ- Symptoms (2,895)

Therapy or tion #1, 50 in ity planning (≥4-point I2: £2000-011,684 Graded Ex- intervention and establish- change): (2,584) ercise Ther- #2, 30 in con- ing a sleep I1: 79% I1+2: £2000-011,830 apy for trol. routine for I2: 73% (2,737)

Chronic Fa- six 45-minute I1+2: 76% C: £2000-011,475 tigue sessions. C: 60% (2,916) (2) Graded (NS) Exercise Therapy tai- Willingness to lored to indi- pay threshold: vidual’s At all values per

347 Somatic Symptoms

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness physical ca- clinically signif- pacity and icant decrease in with gradual fatigue, Cogni- increase in tive Behavioral aerobic activi- Therapy (CBT) ties for six 45- more cost- minute ses- effective than sions. Graded Exercise Therapy (GET). Control*: If value is £0, Usual care 23.7% probabil- plus self-help ity either inter- booklet. vention is more cost-effective *Recruited af- than usual care. ter randomiza- If value is £4.5K, tion. 81.8% probability either inter- Measures: vention is more 8-month fol- cost-effective low-up than usual care. Severens et 128 patients Intervention: Percent Clini- PP: Societal al. (2004) with Chronic (1) Cognitive cally Signifi- Fatigue Syn- Behavioral cant Im- ICER (per Cognitive drome in the Therapy for provement QALY): Behavioral Netherlands. 16 1-hour ses- (CIS – Fatigue I1 vs. I2 Therapy for 37 in interven- sions over 8 Score ≤36): Dominated Chronic Fa- tion, 36 in con- months. I1: 27% tigue Syn- trol #1, 55 in (2) Guided I2: 11% I1 vs. C drome control #2. support C: 20% €21,375 groups for 11 1.5-hour ses- ICER (per one sions over 8 additional im- months. proved patient): I1 vs. C1 Control: Dominated No intervention. I1 vs. C2 €20,532 Measures: 6-month follow-up Chisholm et 129 patients Interventions: Fatigue Score: PP: Societal al. (2001) & with fatigue (1) Cognitive I1: 15.0 (8.5) Risdale et al. symptoms for Behavioral I2: 15.6 (8.0) ICER (per 1- (2001) ≥3 months Therapy on d: .073 point improve-

348 Somatic Symptoms

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness across 10 pri- what perpet- ment in Fatigue Counseling mary care uates rather Mean Change Questionnaire): vs. Cognitive practices in than precipi- in Fatigue I1: £0.6 Behavioral the UK. 64 in tates fatigue Question- I2: -£21.4 Therapy for intervention for 6 1-hour naire: (NS) Chronic Fa- #1, 65 in in- sessions. I1: 7.3 (8.1) tigue tervention #2. Mean cost I2: 8.2 (7.3) Treatment and £164/person. d: .117 healthcare costs (2) Non- I1: £17.5 directive and Percent Fa- I2: £7.9 client-cen- tigue Cases: (NS) tered coun- I1: 53% seling for 6 1- I2: 52% Patient and fami- hour sessions. ly costs Mean cost I1: -£16.9 £109/person. I2: -£29.3 (NS) Measures: 6 months

Irritable Bowel Syndrome (IBS) For Irritable Bowel Syndrome (IBS), two studies compared psychotherapy and pharmacotherapy in the United Kingdom and two tested Internet-based Cogni- tive Behavioral Therapy in Sweden.

For patients with severe IBS, both individual psychotherapy and selective serotonin reuptake inhibitor antidepressant medication (paroxetine) were considered more cost-effective than usual care after a year. While IBS pain improved significantly across all patients, both interventions had greater improvements in health- related quality of life and lower annual healthcare costs than usual care. The cost savings were only significant for psychotherapy, but both interventions could still be considered cost-effective (Creed et al., 2003). In this case, combined psychotherapy and medication was not compared to the individual options.

In another study, the combination of a six session course of Cognitive Behavioral Therapy (CBT) and an antispasmodic medication (mebeverine hydrochloride) was potentially more cost-effective than the medication alone in the short term. After 3 months, cost was estimated at only £171 per clinically significant reduction in IBS symptoms. However, the clinical effects declined over time, leading the incremental cost of achieving clinically significant symptom reductions to increase over time, costing £1,027 after six months and £3,080 after twelve months (McCrone et al., 2008; Kennedy et al., 2006). In this case, CBT alone was not compared to the combined version nor were any of the interventions compared to usual care or no intervention. Moreover, Cognitive Behavioral Therapy interventions were not continued following the initial 6-session treatment. It is unknown

349 Somatic Symptoms whether clinical benefits would have been better maintained with on-going booster sessions or other maintenance-focused CBT interventions.

For Internet-based CBT, the first study targeted patients already attending a gastroenterological clinic and the second recruited participants online. For clinic patients, Internet-based CBT with therapist support for ten weeks significantly improved gastrointestinal symptoms immediately post-treatment and was cost- saving over waiting list control, saving $39,821 per significant clinical improvement in IBS (≥50% reduction in symptoms; Ljótsson et al., 2011). For online participants, Internet-based CBT with therapist support for ten weeks was similarly effective at improving symptoms and similarly cost-saving over an Internet discussion forum (with option to contact therapist via email), saving $16,806 per significant clinical improvement in IBS. In this case, cost-effectiveness was also confirmed after three months and one year (Andersson et al., 2011).

Table 3. Behavioral Interventions for Irritable Bowel Syndrome (IBS) Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Ljótsson et 50 patients Intervention: Gastrointes- PP: Societal al. (2011) with IBS in a Internet- tinal Symp- gastroentero- based Cogni- tom Rating ICER (per ≥50% Internet- logical clinic tive Behav- Scale – IBS reduction in based Cogni- in Sweden. 23 ioral Therapy (GSRS-IBS): GSRS-IBS): tive Behav- in interven- guided by an I: 31.0 (10.2) -$39,821 ioral Thera- tion, 27 in con- online thera- C: 40.9 (14.5) py with clin- trol. pist for 10 (p<.001) ical sample weeks. d: .802 Control: Waiting list. Irritable Bowel Syn- Measures: drome Quali- Post- ty of Life intervention (IBS-QoL): I: 82.6 (13.4) C: 67.4 (23.1) d: .833 Andersson et 85 participants Intervention: Percent Re- PP: Societal al. (2011) with IBS re- Internet- covered Par- cruited online based Cogni- ticipants ICER (per ≥50% Internet- in Sweden. 42 tive Behav- (≥50% reduc- reduction in based Cogni- in interven- ioral Therapy tion in Gas- GSRS-IBS): tive Behav- tion, 43 in con- with therapist trointestinal -$200816,806 ioral Thera- trol. support via Symptom py with email for 10 Rating Scale – online sam- weeks. IBS; GSRS- ple IBS): Control: I: 36% Internet dis- C: 2%

350 Somatic Symptoms

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness cussion fo- (p<.01) rum with option to email therapist for support.

Measures: Post- intervention McCrone et 149 patients Intervention: Difference in PP: Treatment al. (2008) & (age 17-54 Standard Means on IBS Kennedy et years) with treatment Symptom Se- ICER (per clini- al. (2006) IBS across ten with anti- verity Scale: cally significant primary care spasmodic 3-month fol- reduction in IBS Cognitive practices with agent low-up symptoms): Behavioral in UK. 82% (mebeverine -71 (95% CI, - 3-month follow- Therapy plus female. 72 in hydrochlo- 109 to -32) up antispas- intervention, ride) plus £1999171 modic medi- 77 in control. Cognitive 6-month fol- cation versus Behavioral low-up 6-month follow- anti- Therapy with -14 (95% CI, - up spasmodic trained nurs- 51 to 23) £19991,027 medication es for up to 12-month fol- 12-month follow- alone six 50-minute low-up up

sessions. Av- 3 (95% CI, -35 £19993,080 erage addi- to 40) tional cost £308/patient.

Control: Standard treatment with antispasmodic agent (mebeverine hydrochloride) alone.

Measures: 3-, 6- and 12- month follow-up Creed et al. 249 patients Interventions: Visual Ana- PP: Healthcare (2003) (age 18-65 (1) Individual logue of Pain: years) with psychothera- I1: 15.0 (SE Annual Costs:

351 Somatic Symptoms

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness

Costs of psy- severe IBS in py for 8 ses- 3.55) I1: $1998976 (984) chotherapy UK. 80 in in- sions over 3 I2: 16.3 (SE I2: $19981,252 verses par- tervention #1, months. 69% 3.18) (1,616) oxetine for 86 in interven- completed. C: 15.6 (SE C: $19981,663 severe IBS tion #2, 83 in (2) Selective 3.19) (3,177) control. serotonin reuptake in- d1: .020 d1: .330 hibitor anti- d2: .024 d2: .172 depressant (paroxetine) SF-36 Physi- Weekly Costs:

over 3 cal Compo- I1: $199823.12 months. 50% nent Score: (16.21)

completed. I1: 5.2 (SE I2: $199825.38 1.26) (25.84)

Control: I2: 5.8 (SE C: $199830.29 Routine care. 1.00) (52.10) C: -0.3 (SE Measures: 1.17) d1: .210 1-year follow- d2: .126 up d1: .432 d2: .552

LIMITATIONS AND FUTURE DIRECTIONS The limitations of the literature on cost-effective treatment of Somatic Symptom Disorders and related syndromes such as Chronic Fatigue Syndrome and Irrita- ble Bowel Syndrome are numerous. The lack of understanding around underlying mechanisms, lack of consistency around diagnosis, and lack of effective behavioral interventions all contribute to high associated costs including increased healthcare utilization and workplace absenteeism. Furthermore, these limitations have thus far prevented adequate estimates of the overall prevalence and economic burden to illuminate the full toll of these distressing chronic somatic symptoms in the United States.

One of the biggest drivers of these increased costs is the psychological distress associated with the desire for an explanation and lack of diagnosis to explain it. Among other things, this can lead to more healthcare costs as well as more time off of work as the person consults multiple physicians, insists on additional screenings and tests, or receives unnecessary treatments. However, psychosocial interventions that shift focus from the cause or elimination of the somatic symptoms to the management of them have the potential to play an important role in increasing functioning and improving quality of life, as well as reducing the strain on the healthcare system and society at large.

Clearly, diagnosis remains an issue; for instance, at least one study suggested more than 75% of persons with Irritable Bowel Syndrome did not have a formal diagnosis. Insofar as one of these diagnoses may also help alleviate the associat-

352 Somatic Symptoms ed psychological distress, it warrants further investigation and possible integration into standard practice. Of course, the risk of over-diagnosis or misdiagnosis that overlooks underlying cause(s) remains high. In such cases, psychosocial interventions may still have a place in interim symptom management. Regardless, it is imperative to establish a clear standard of care for these patients.

Many treatment protocols and guidelines target specific symptoms yet general psychosocial interventions may contribute significantly to overall cost- effectiveness. More studies need to compare interventions to each other as well as to usual care or no intervention. Further, cost-effectiveness data for behavioral interventions are lacking for other significant chronic somatic symptoms (e.g., headaches). In short, much remains to be done to understand and manage chronic somatic symptoms to maximize benefit and minimize costs.

KEY POINTS Somatic Symptom Disorder • Mindfulness-Based Cognitive Therapy in groups was less cost-effective than usual care per QALY after nine months. • Mindfulness Therapy in groups and enhanced usual care (psychiatric consultation and treatment plan) appeared equally cost-effective to each other after 15 months. Both interventions had similar clinical effects and significantly decreased healthcare costs. It is possible these cost-savings outweigh implementation costs, but comparisons to usual care or no intervention are needed. • Group Therapy appeared more cost-effective than enhanced usual care (physician consultation letter) after a year, with improvements in physical and mental health outcomes and reductions in healthcare costs, despite only 45% of participants assigned to Group Therapy attending at least one session of it. • A multicomponent collaborative stepped care program including Cognitive Behavioral Therapy, medication management, and positive physician-patient relationships for one year led to significant clinical improvements without increasing healthcare costs after two years, suggesting cost-effectiveness.

Chronic Fatigue Syndrome (CFS) • Cognitive Behavioral Therapy (CBT) dominated guided support groups at all values and has the potential to be more cost-effective than no intervention per QALY and per additional improved patient after six months, depending on willingness to pay thresholds. • CBT seemed equally cost-effective to non-directive Counseling since both had clinical improvements and cost reductions after six months, but neither were compared to usual care or no intervention to assess overall cost-effectiveness. • CBT was more cost-effective than Graded Exercise Therapy at all values after eight months. As before, CBT may be more cost-effective than no intervention depending on the willingness to pay threshold.

Irritable Bowel Syndrome (IBS) • Both psychotherapy and paroxetine (a selective serotonin reuptake inhibitor antidepressant) alone improved health-related quality of life and decreased

353 Somatic Symptoms

costs relative to usual care after a year, suggesting both were equally cost- effective to each other and more cost-effective than usual care, although the cost differences were only significant for psychotherapy. • Combined Cognitive Behavioral Therapy (CBT) and mebeverine hydrochloride (an antispasmodic agent) could be more cost-effective than mebeverine hydrochloride alone in the first three months per clinically significant improvement in IBS symptoms, but was less cost-effective per improvement at six months and 12 months. • Internet-based CBT with therapist support was cost-saving compared to waitlist control, saving $39,821 per significant clinical improvement in IBS at post- intervention for patients in a gastroenterological clinic. It was similarly cost- saving compared to an online discussion forum, saving $16,806 per significant clinical improvement in IBS at post-intervention for patients recruited online. The intervention continued to be cost-effective and cost-saving at three and 12 months.

REFERENCES American Psychiatric Association. “Somatic Symptom and Related Disorders.” Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. May 2013.

Andersson E, Ljótsson B, Smit F, Paxling B, Hedman E, Lindefors N, Andersson G, Rück C. Cost-effectiveness of Internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial. BMC Pub- lic Health. 2011 Apr 7;11:215.

Barsky AJ, Orav EJ, Bates DW. Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity. Arch Gen Psychiatry. 2005 Aug;62(8):903-10.

Canavan C, West J, Card T. Review article: the economic impact of the irritable bowel syndrome. Aliment Pharmacol Ther. 2014 Nov;40(9):1023-34.

Cash B. Economic impact of irritable bowel syndrome: what does the future hold? Am J Manag Care. 2005 Apr;11(1 Suppl):S4-6.

Chisholm D, Godfrey E, Ridsdale L, Chalder T, King M, Seed P, Wallace P, Wes- sely S; Fatigue Trialists' Group. Chronic fatigue in general practice: economic evaluation of counselling versus cognitive behaviour therapy. Br J Gen Pract. 2001 Jan;51(462):15-8.

Creed F, Fernandes L, Guthrie E, Palmer S, Ratcliffe J, Read N, Rigby C, Thomp- son D, Tomenson B; North of England IBS Research Group. The cost- effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology. 2003 Feb;124(2):303-17.

Dinos S, Khoshaba B, Ashby D, White PD, Nazroo J, Wessely S, Bhui KS. A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping. Int J Epidemiol. 2009 Dec;38(6):1554-70.

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Fjorback LO, Carstensen T, Arendt M, Ornbøl E, Walach H, Rehfeld E, Fink P. Mindfulness therapy for somatization disorder and functional somatic syndromes: analysis of economic consequences alongside a randomized trial. (2013a). J Psychosom Res. 2013 Jan;74(1):41-8.

Fjorback LO, Arendt M, Ornbøl E, Walach H, Rehfeld E, Schröder A, Fink P. Mindfulness therapy for somatization disorder and functional somatic syndromes: randomized trial with one-year follow-up. (2013b). J Psychosom Res. 2013 Jan;74(1):31-40.

Hungin AP, Chang L, Locke GR, Dennis EH, Barghout V. Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Aliment Pharmacol Ther. 2005 Jun 1;21(11):1365-75.

Inadomi JM, Fennerty MB, Bjorkman D. Systematic review: the economic impact of irritable bowel syndrome. Aliment Pharmacol Ther. 2003 Oct 1;18(7):671-82.

Jason LA, Benton MC, Valentine L, Johnson A, Torres-Harding S. The economic impact of ME/CFS: individual and societal costs. Dyn Med. 2008 Apr 8;7:6.

Johnston S, Brenu EW, Staines D, Marshall-Gradisnik S. The prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis: a meta-analysis. Clin Epidemi- ol. 2013;5:105-10.

Kashner TM, Rost K, Cohen B, Anderson M, Smith GR Jr. Enhancing the health of somatization disorder patients. Effectiveness of short-term group therapy. Psychosomatics. 1995 Sep-Oct;36(5):462-70.

Kennedy TM, Chalder T, McCrone P, Darnley S, Knapp M, Jones RH, Wessely S. Cognitive behavioural therapy in addition to antispasmodic therapy for irritable bowel syndrome in primary care: randomised controlled trial. Health Technol Assess. 2006 Jun;10(19):iii-iv, ix-x, 1-67.

Lin JM, Resch SC, Brimmer DJ, Johnson A, Kennedy S, Burstein N, Simon CJ. The economic impact of chronic fatigue syndrome in Georgia: direct and indirect costs. Cost Eff Resour Alloc. 2011 Jan 21;9(1):1.

Ljótsson B, Andersson G, Andersson E, Hedman E, Lindfors P, Andréewitch S, Rück C, Lindefors N. Acceptability, effectiveness, and cost-effectiveness of Inter- net-based exposure treatment for irritable bowel syndrome in a clinical sample: a randomized controlled trial. BMC Gastroenterol. 2011 Oct 12;11:110.

Luo Z, Goddeeris J, Gardiner JC, Smith RC. Costs of an intervention for primary care patients with medically unexplained symptoms: a randomized controlled trial. Psychiatr Serv. 2007 Aug;58(8):1079-86.

Maxion-Bergemann S, Thielecke F, Abel F, Bergemann R. Costs of irritable bowel syndrome in the UK and US. Pharmacoeconomics. 2006;24(1):21-37.

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McCrone P, Knapp M, Kennedy T, Seed P, Jones R, Darnley S, Chalder T. Cost- effectiveness of cognitive behaviour therapy in addition to mebeverine for irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2008 Apr;20(4):255-63.

McCrone P, Ridsdale L, Darbishire L, Seed P. Cost-effectiveness of cognitive behavioural therapy, graded exercise and usual care for patients with chronic fatigue in primary care. Psychol Med. 2004 Aug;34(6):991-9.

Reynolds KJ, Vernon SD, Bouchery E, Reeves WC. The economic impact of chronic fatigue syndrome. Cost Eff Resour Alloc. 2004 Jun 21;2(1):4.

Ridsdale L, Godfrey E, Chalder T, Seed P, King M, Wallace P, Wessely S; Fatigue Trialists' Group. Chronic fatigue in general practice: is counselling as good as cognitive behaviour therapy? A UK randomised trial. Br J Gen Pract. 2001 Jan;51(462):19-24.

Saito YA, Schoenfeld P, Locke GR 3rd. The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002 Aug;97(8):1910-5.

Severens JL, Prins JB, van der Wilt GJ, van der Meer JW, Bleijenberg G. Cost- effectiveness of cognitive behaviour therapy for patients with chronic fatigue syndrome. QJM. 2004 Mar;97(3):153-61.

Smith RC, Lyles JS, Gardiner JC, Sirbu C, Hodges A, Collins C, Dwamena FC, Lein C, William Given C, Given B, Goddeeris J. Primary care clinicians treat patients with medically unexplained symptoms: a randomized controlled trial. J Gen Intern Med. 2006 Jul;21(7):671-7.

Spiegel BM. The burden of IBS: looking at metrics. Curr Gastroenterol Rep. 2009 Aug;11(4):265-9. van Ravesteijn H, Grutters J, olde Hartman T, Lucassen P, Bor H, van Weel C, van der Wilt GJ, Speckens A. Mindfulness-based cognitive therapy for patients with medically unexplained symptoms: a cost-effectiveness study. J Psychosom Res. 2013 Mar;74(3):197-205.

356 Chronic Pain

CHAPTER 16: CHRONIC PAIN

ABSTRACT Chronic pain is complex and can persist for months or years and cause significant impairment in physical, emotional, social and occupational function. Chronic pain can result from obvious physical damage, but may also be associated with undetectable injuries.

Prevalence estimates range immensely from 2% to 64%, with more than half of sufferers experiencing lower back pain and three-quarters experiencing pain in multiple body regions (which may include the lower back). The annual economic burden was estimated at $560 to $635 billion, about half due to healthcare costs and half due to lost productivity. Since maladaptive patterns of thoughts, emotions, and behaviors can worsen pain severity and prevent recovery, many interventions include a cognitive or cognitive behavioral approach. To prevent chronic pain, a biopsychosocial intervention for acute jaw and face pain and a functional restoration early intervention for acute low back pain were both significantly more effective and less expensive than no intervention. For chronic low back pain, adding a cognitive behavioral intervention was more cost- effective than an educational booklet and audiocassette alone; more cost-effective than active management alone; cost-saving over inpatient rehabilitation alone; and equally cost-effective as adding a group discussion to an operant treatment. Meanwhile a behavioral graded activity intervention could be more cost-effective than standard physical therapy and than both combined, while physical therapy was more cost-effective than advice about physical therapy.

For chronic spinal pain, a brief cognitive behavioral program was less effective and less expensive than traditional physical therapy across two studies, with cost-effectiveness for physical therapy within a standard willingness to pay threshold in one study but not the other. For chronic widespread pain, telephone-based Cognitive Behavioral Therapy (CBT) was more cost-effective than a graded exercise program, both CBT and graded exercise combined, and usual care, while Internet-based CBT was cost-saving over in-person CBT. For fibromyalgia, adding group discussion was more cost-effective than adding Cognitive Therapy to group education. A subset of studies focused on return-to- work programs for persons taking pain-related sick leave. For chronic low back pain, an integrated workplace intervention plus cognitive behavioral graded activity program dominated usual care as cost-saving, and a cognitive behavioral graded activity program alone had the potential to be more cost-effective than usual care. Similarly, a workplace intervention including workplace assessment, work modifications, and case management was more cost-effective than usual care; for individuals who did not recover in either treatment after eight weeks, adding a clinical intervention of operant-based graded physical therapy was less cost-effective than usual care. For chronic spinal pain, behavior-oriented physical therapy, CBT, or both combined were similar in efficacy and costs; however, only the program including behavior-oriented physical therapy plus CBT, in the female subpopulation, was cost-effective. For musculoskeletal disorders (not specific to chronic pain), the addition of cognitive behavioral treatment to rheumatologic care compared to rheumatologic care alone was cost-saving.

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Finally, total disc replacement surgery appeared to be more cost-effective than multidisciplinary rehabilitation for chronic low back pain due to degenerative disc disease at two-year follow-up, and traditional physical therapy was more cost-effective than a behavioral graded activity program for pain following first- time lumbar disc surgery.

Overall, there are compelling data for behavioral and cognitive behavioral interventions as cost-effective and cost-saving for chronic pain, and further refinement should be able to elucidate the elements and delivery formats that are most cost-effective and explain findings that do not support this broad conclusion.

BACKGROUND ON CHRONIC PAIN In general, acute (i.e. short duration) pain is directly related to tissue damage and can be a useful signal of potential harm to the body. However, chronic (i.e. long duration) pain can persist for days, months, or years with or without on-going tissue damage. Chronic pain can be triggered by a specific injury or accompany chronic conditions like arthritis and cancer, but it can also have no initial physical cause or continue long after the initial tissue damage (see Chapter 15 on Chronic Somatic Symptoms for further details on medically unexplained symptoms). Rather than indicating on-going damage to peripheral tissues, chronic pain may be produced by, for example, maladaptive learning in neural circuits involved in sensory or threat detection, or damage to nerves or neural circuits (e.g. by viral infection, injury, inflammation, or malfunction). Chronic pain can manifest as widespread or localized pain. Common complaints include back pain, neck pain, and headaches. At least half of all people who report localized chronic pain experience back pain (Hardt et al., 2008).

Briefly, pain falls into two broad categories: nociceptive pain (related to tissue damage) and neuropathic pain (related to nerve damage). Both types of pain can be caused by injury, malfunction, or disease. Nociceptive pain is often localized acute pain, such as muscle aches, throbbing, tenderness, etc. Neuropathic pain is often diffuse chronic pain, which includes typically non-painful stimuli becoming painful and abnormal sensations such as stabbing, burning, numbing, tingling, and/or prickling. These sensations can be constant or episodic, occurring in waves of frequency and intensity. Since neural circuits detect, transmit, interpret and initiate responses to pain, chronic pain may occur if these circuits continue to be active even after the initial injury is no longer present.

Musculoskeletal disorders, which are one of the primary contributors to chronic pain, refer to any injury, damage or pain related to a person’s muscles, joints, tendons, nerves, and related supporting structures for the limbs, necks, and lower back. These can be triggered or worsened by physical factors like sudden exertion or repetition (e.g., leading to carpel tunnel syndrome or tendonitis), but do not include sudden physical contact such as accidents. Temporomandibular joint disorders are similar but focused exclusively on pain or discomfort with the muscles and joints that move the jaw (e.g., those involved with chewing).

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Fibromyalgia is a type of chronic pain that includes widespread musculoskeletal pain and increased pain sensitivity (e.g. tender points), which may be accompanied by other symptoms related to fatigue, sleep problems, mood, cognition, memory, and sensitivity to temperature, sound or light. Many of these symptoms are similar to Chronic Fatigue Syndrome (see Chapter 15), with an emphasis on pain rather than fatigue. As with many chronic somatic symptoms, a triggering cause may or may not exist. For example, some people posit a traumatic physical or emotional experience might contribute to the onset of fibromyalgia; others are investigating potential genetic differences in the way the body responds to painful stimuli. Notably, fibromyalgia occurs more frequently in females than males.

To date, there is no standardized definition of chronic pain. This impacts criteria used to select study participants and in addition complicates estimates of prevalence and economic burden. The key factor is duration (usually minimum of three or six months), but frequency and/or intensity may also be included. Chronic pain is complex because pain is a subjective experience. In other words, the same stimuli can lead to different intensities of pain for different individuals. The biopsychosocial model of pain acknowledges the intersection of physiological, psychological, and social factors with physical pathology to create the individual’s unique experience of pain (Gatchel & Peng, 2012).

Moreover, fluctuations in pain severity can shape habits of thought, emotion, and behavior, as increases in pain encourage avoidance and decreases in pain encourage repetition of states that precede the change in pain severity. Insofar as work, exercise, social activities, and other life activities immediately worsen pain, and inactivity or substance use immediately reduce pain, chronic pain can lead to habits that prevent recovery and impair physical and psychosocial function.

PREVALENCE Estimates for the prevalence of chronic pain in the United States range from 2% to 64.4%, with a median prevalence of 15% (Gaskin & Richard, 2012; Johannes et al., 2010). One recent representative study estimated prevalence at 3.6% for widespread pain and 11.0% for localized pain as of 2002, which the authors noted were lower than prior U.S. estimates (Gaskin & Richard, 2012). A recent Internet-based representative study found almost a third of the population (30.7%) experienced chronic pain for at least six months, with 48% reporting lower back pain, 38% knee joints, 28% neck, 27% shoulder joints, 27% legs/feet other than joint pain, 25% hip joints, and 25% feet joints. Notably, a third of those with chronic pain did not have a diagnosed pain condition (Johannes et al., 2010).

Prevalence of chronic pain increases with age before stabilizing or decreasing during older age (Hardt et al., 2008; Johannes et al., 2010), suggesting a clear impact on the most productive working years. In addition to impacting functional abilities (e.g., workplace absenteeism), chronic pain also impacts psychological wellbeing and quality of life. Importantly, chronic pain can be recurrent, intermittent, or episodic, with the Internet-based study finding the majority experienced chronic pain at least two to three times per week (85%) for at least a year (89%), indicating the long lasting and persistent effects.

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Overall, chronic pain frequently co-occurs with other disorders. Most people (75%) with chronic pain report pain in more than one body location (Johannes et al., 2010). For those with chronic spinal pain (i.e. back or neck pain), most (87.1%) report a co-occurring condition. In particular, 68.6% have another chronic pain condition, 55.3% another physical condition, and 35.0% a neuropsychiatric condition. Within co-occurring neuropsychiatric conditions, 26.5% have an anxiety disorder, 17.5% have a mood disorder (12.6% major depression), and 4.8% have a substance use disorder (Von Korff et al., 2005).

ECONOMIC BURDEN OF CHRONIC PAIN The economic burden of pain was estimated at $560 to $635 billion annually as of 2010, with almost half ($261 to $300 billion) due to additional healthcare costs and the other half ($299 to $335 billion) due to lost productivity costs. These costs exceeded those for heart disease ($309 billion), cancer ($243 billion), and diabetes ($188 billion). Notably, both direct and indirect costs increased as pain severity increased: annual healthcare costs per person were $3,210 higher for severe pain over moderate pain and annual lost productivity per person included 717 fewer hours of work and 2.6 more days off from work for severe pain over moderate pain (Gaskin & Richard, 2012).

These high costs can be explained in part by the fact that chronic pain is one of the most common symptoms for which people seek medical care (Hardt et al., 2008; Johannes et al., 2010). Chronic pain also complicates treatment for other medical conditions. Back pain, in particular, has been identified as the third most common cause of surgical procedures and fifth most common cause of hospitalizations. Back pain is also the main reason that adults (less that 45 years old) limit their physical activity. In general, chronic pain hinders a person’s ability to work and to function in society, leading to workplace absenteeism and/or presenteeism (i.e. attending work while sick) and corresponding decreased wages and increased disability and injury compensation (Pai & Sundaram, 2004).

CLINICALLY EFFECTIVE INTERVENTIONS The complexities of chronic pain are mirrored in the complexities of treatment. Given there are often no identifiable tissue injuries producing chronic pain, behavioral treatments often focus on improving function and reducing or managing the experience of pain by focusing less on the source of pain than the perception of it and response to it. Since chronic pain varies immensely and each person experiences pain differently, key recommendations include early, individually tailored, and multimodal interventions when possible. However, efficacy remains highly variable.

Treatments for localized pain can include physical therapy or similar interventions, but treatments for non-localized pain are more difficult. In general, interventions to manage the perception and functional impact of pain often include a combination of pharmaceuticals and psychosocial tools. Interventions can also include, for example, acupuncture, brain stimulation, electrical nerve stimulation, and surgery, which will not be reviewed in detail here.

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For pharmacotherapy, most recommendations are tailored to the specific type of pain. Importantly, given the addictive and/or sedative properties of some of these medications, close supervision is critical. To immediately reduce pain symptoms, recommendations include non-steroid anti-inflammatory drugs (NSAIDs); however, these should not be used for long-term maintenance. When other treatment options have failed, opioid therapy may be recommended. However, since opioid medications comes with significant risk of mortality from respiratory depression, sexual dysfunction, and other adverse effects, the potential risks and benefits must be weighed for each patient and continued use is only recommended if the patient experiences functional improvements. Other medications have been found effective for some specific pain conditions (e.g. neuropathic pain, arthritis), including some tricyclic antidepressants, serotonin- norepinephrine reuptake inhibitors, anticonvulsants, and topical agents such as capsaicin cream.

Chronic overuse and misuse or abuse of opioid analgesics is a major concern. The reinforcing properties of opioid medications can encourage on-going use even when they do not produce objective, long-term, or clinically significant improvements in functionality or pain severity. Given the negative consequences outlined earlier, continued use without objective benefit is especially problematic. Additionally, a minority of patients will intentionally misuse opioid medications (e.g., taking it for its mood-altering effects); for example, by tampering with the medication formulation. Psychosocial interventions not only provide a safer and potentially more effective option for pain management, they may also develop effective coping skills that can improve function and pain, and reduce reliance on medications.

Psychosocial interventions include Cognitive Behavioral Therapy, Biofeedback, Relaxation Training, Supportive Psychotherapy, Group Therapy, and Generic Counseling. Cost-effectiveness studies focused on cognitive behavioral interventions. For chronic pain, cognitive behavioral strategies include psychoeducation about how cognitions and behaviors can affect the pain experience and skills training to cope with or control the pain experience, such as relaxation exercises, graded physical activity to increase frequency and intensity of activity, and cognitive restructuring of negative pain-related thoughts.

COST-EFFECTIVENESS OF INTERVENTIONS A prior review of the cost-effectiveness of physical, pharmacological, and psychosocial interventions for chronic pain found that none of the interventions consistently eliminated pain or improved functional outcomes but that some reduced or managed pain. Expensive physical interventions (e.g., surgery, spinal cord stimulators, implantable drug delivery systems) may be cost-effective for a subset of carefully selected patients. Pain rehabilitation programs were significantly more cost-effective than both these physical interventions and usual care, with a range of improvements from healthcare utilization to functionality. However, the researchers noted the difficulties of comparison due to differences in patient populations and their pain symptoms. More research is needed to illuminate which treatments are best for which patients (Turk, 2002).

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In this review of behavioral interventions, we identified two broad categories of relevant outcomes: 1) pain management and quality of life, and 2) return-to-work after workplace absenteeism. While some studies include both categories of outcomes, we select their primary focus. At the end, we also include a brief section on surgery and post-surgical pain. Overall, most studies focus on chronic low back pain, with a few studies for spinal pain and widespread pain.

Pain Management Prevention Interventions The only cost-effectiveness study on temporomandibular joint disorders identified persons with acute face or jaw pain at high risk for chronic pain. For these patients, an early biopsychosocial intervention including cognitive behavioral skills training and biofeedback appeared more cost-effective than no intervention after a year, with significant differences in clinical efficacy and costs. The biopsychosocial intervention decreased self-reported pain and depressive symptoms, improved problem-focused ways of coping, and had significantly lower jaw-related healthcare costs per person ($132 versus $434; Stowell et al., 2007).

Table 1. Prevention Interventions for Chronic Pain Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Stowell et al. 96 patients at Intervention: Characteristic PP: Healthcare (2007) high risk of Early Pain progressing biopsychosoc Inventory Jaw-Related Early from acute to ial (CPI): Healthcare biopsychoso chronic intervention I: 22.29 Costs (per cial temporomand during acute (18.21) patient): intervention ibular phase of C: 34.36 I: $131.67 for disorder- disorder (23.95) C: $433.75 temporoman related pain including (p=.01) (p=.029) dibular (i.e. face or cognitive d: .573 disorders jaw pain) in behavioral the U.S. 57 in skills training Beck intervention, and Depression 39 in control. biofeedback Inventory-2 for 6 sessions. (BDI-2): I: 5.33 (7.11) Control: C: 8.72 (9.71) No (p=.05) intervention. d: .403

Measures: Problem- 1-year follow- Focused up Ways of Coping (WOC):

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness I: 24.98 (3.41) C: 23.37 (4.02) (p=.04) d: .433

Treatment Interventions Most behavioral interventions for chronic pain management are similar regardless of the type of chronic pain. Notably, none of the following cost- effectiveness studies for chronic pain management are from the United States.

Chronic Low Back Pain Several studies for chronic low back pain compared the addition of cognitive behavioral interventions to existing standard ones. For disabling low back pain in the United Kingdom, adding a cognitive behavioral intervention including a group exercise program to an educational booklet and audiocassette was more cost-effective than the booklet and audiocassette alone after a year. It only cost $8,650 per QALY, well within standard willingness to pay thresholds. If the value were $51,900 per QALY, there was 90% likelihood that adding the cognitive behavioral intervention was more cost-effective than the educational booklet and audiocassette alone (Johnson et al., 2007).

For sub-acute (i.e. between acute and chronic) and chronic low back pain in the United Kingdom, adding a cognitive behavioral intervention with professionally led groups to active management was more cost-effective than active management alone after a year at £3,093 per QALY, which is also well within standard willingness to pay thresholds. Further analyses revealed cost- effectiveness might only apply to persons with moderate and/or high severity of pain; when limited to persons with low severity of pain, active management alone dominated the addition of the cognitive behavioral intervention (Lamb et al., 2010).

Meanwhile, for chronic low back pain in Germany, adding a cognitive behavioral pain management program to inpatient rehabilitation was cost-saving over inpatient rehabilitation alone at €126,731 saved per QALY after six months. The standard inpatient rehabilitation program included exercise, physical therapy, massage, electrotherapy, and education. While there were no significant clinical differences on pain and discomfort outcomes, the cost savings of the cognitive behavioral program were driven by a significant decrease in the number of days off from work (Schweikert et al., 2006). This is similar to findings in the return-to- work section later on.

For patients with chronic low back pain for an average of ten years (minimum six months) in the Netherlands, adding a cognitive behavioral treatment to an operant treatment (i.e. behavior modification to increase healthy behaviors and activity levels and decrease pain behaviors and excess disability) was not significantly different from adding a matched-control group discussion for

363 Chronic Pain clinical outcomes or costs after three years; however, comparisons were made to operant treatment alone, so overall cost-effectiveness cannot be assessed at this time (Goossens et al., 1998; Kole-Snijder et al., 1999).

In the Netherlands, a behavioral intervention including graded activity training and problem-solving training was more cost-effective than a physical intervention including group training for aerobics and for strength and endurance, as well as more cost-effective than both interventions combined after a year at all willingness to pay thresholds. Specifically, the behavioral intervention was cost-saving at €108,857 saved per QALY over the combined intervention, while the physical intervention still cost $35,060 more per QALY over the combined intervention. However, these differences were less apparent in terms of self-reported disability, with both the behavioral and physical interventions demonstrating similar clinical efficacy over the combined intervention (Smeets et al., 2009).

Finally, for sub-acute and chronic low back pain in the United Kingdom, physical therapy for one to six sessions was more cost-effective than advice about physical therapy for one session at only £3,010 per QALY after twelve months. If the value were £5,000 per QALY, there was 60% likelihood that physical therapy was more cost-effective; as the value increased, this likelihood never exceeded 73% (Rivero- Arias et al., 2006; Frost et al., 2004).

Table 2. Behavioral Interventions for Chronic Low Back Pain Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Lamb et al. 490 patients Intervention: Modified Von PP: Healthcare (2010) with sub-acute Active Korff Scale and chronic management (MVK): ICER (per Back Skills low back pain plus group- Disability QALY):

Training across 56 based subscale £20083,093 (BeST) with clinics in UK. cognitive I: 33.3 (26.22) a cognitive 327 in behavioral C: 40.0 (25.22) Willingness to behavioral intervention, program for pay thresholds: program for 163 in control. up to six 90- d: .260 If value is low back minute £5K/QALY, pain weekly Pain subscale 89% probability sessions. I: 44.5 (26.04) active manage- C: 51.0 (23.93) ment plus cog- Control: d: .260 nitive behavior- Active al program management Roland more cost- alone for ~15 Disability effective than minutes. Questionnair active manage- e (RDQ): ment alone. If Measures: I: 6.1 (5.62) value is £10K, 12 months C: 6.9 (5.12) 99% probability d: .149 more cost-

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness effective. Smeets et al. 133 patients Interventions: Improvement PP: Societal (2009) with chronic (1) Active in Roland low back pain physical Disability ICER (per Behavioral in the group Questionnair QALY): and physical Netherlands. treatment e (RDQ): I1 vs. I3 rehabilitatio 49 in with 30- I1: 3.21 (4.77) €200335,060 n programs intervention minute I2: 3.25 (4.29) for chronic #1, 39 in aerobic I3: 1.98 (4.55) I2 vs. I3 low back intervention training and -€2003108,857 pain #2, 45 in 75-minute d1 (I1 vs. I3): intervention strength and .264 ICER (per 1- #3. endurance d2 (I2 vs. I3): point training .287 improvement in 3x/week for RDQ): 10 weeks. I1 vs. I3

(2) Graded €2003371 activity training to I2 vs. I3

increase -€20033,759 frequency/pa cing of Willingness to activities plus pay threshold: problem- In terms of solving QALY, graded training with activity training 3 initial most likely to be group more cost- sessions and effective than up to 17 active physical individual 30- treatment and minute combined sessions for treatment at all 10 weeks. willingness to (3) Both I1 pay thresholds. and I2 In terms of combined for RDQ, combined 10 weeks. treatment always less cost- Control: effective than Waiting list. either treatment alone. As Measures: willingness to 52 weeks pay threshold increases, graded activity

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness training and active physical treatment approach each other. Johnson et 149 patients Intervention: Visual PP: Intervention al. (2007) (age 18-65 Cognitive Analogue years) with Behavioral Scale (VAS; ICER (per Active persistent Therapy- pain QALY): exercise, disabling low based group severity): $2003-20048,650 education, back pain in program of I: 27.9 (26.1) and UK. 78 in exercise and C: 36.4 (27.3) Willingness to Cognitive intervention, education pay threshold: Behavioral 71 in control. with eight 2- d: .318 At value of Therapy for hour group $51.9K/QALY, persistent sessions over Roland and 90% probability disabling 6 weeks plus Morris adding low back educational Disability cognitive pain in booklet and Scale behavioral primary care audiocassette. (RMDQ): group program I: 6.7 (5.6) more cost- Control: C: 8.0 (5.5) effective than Educational educational booklet and d: .234 booklet and audiocassette. audiocassette alone. Measures: 12 months Schweikert 264 patients Intervention: Days Off PP: Societal et al. (2006) with chronic Standard 3- Work Due to low back pain week in- Spinal ICER (per Adding in inpatient patient Complaints: QALY): cognitive rehabilitation rehabilitation I: 11.4 (28.9) -€2001126,731 behavioral in Germany. plus C: 16.8 (34.1) treatment to 117 in cognitive- inpatient intervention, behavioral d: .171 rehabilitatio 147 in control. pain manage- n for chronic ment prgram EuroQOL: low back of six 1.5- I: 66.8 (18.8) pain hour group C: 62.9 (19.8) sessions. Average cost d: .202 €127/patient. No significant Control: differences in Standard 3- any pain or

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness week in- discomfort patient outcomes. rehabilitation only.

Measures: 6-month follow-up Rivero-Arias 286 patients Interventions: Oswestry PP: Healthcare et al. (2006) with sub-acute (1) Routine Disability & Frost et al. and chronic physical Index: ICER (per (2004) low back pain therapy treat- I1: -3.27 QALY):

for more than ment with a (10.99) £20043,010 Physical 6 weeks in 1-hour I2: -2.23 therapy UK. 144 in session and (11.47) Willingness to versus intervention up to five 30- d: .093 pay threshold: physical #1, 142 in minute If value is therapy intervention sessions. Roland and £5K/QALY, advice for #2. (2) Assess- Morris 60% probability low back ment session Disability routine physical pain and advice to Questionnair therapy more remain active e: cost-effective for 1 session I1: -1.36 (4.66) than assessment lasting up to I2: -.99 (4.23) and advice. As 1 hour. d: .083 value increases, probability does Measures: not exceed 73%. 12-month follow-up Goossens et 148 patients Interventions: Post- PP: Societal al. (1998) & (age 18-65 Operant treatment Kole-Snijders years) with treatment to Improvement Total Costs: et al. (1999) chronic low increase in value of Program costs

back pain for healthy current I1: $19939,196 Behavioral more than 6 behaviors health state I2: $19938,607 rehabilitatio months and and activity (Scale from 0- C: $19938,667 n in chronic average of 10 levels and 100): low back years in the decrease pain 1 versus Direct healthcare pain Netherlands. behaviors waitlist: 95% costs

64% female. 59 and excess CI: 7.85-24.18 I1: $19931,088 in intervention disability in 8 2 versus (1,812)

#1, 58 in weekly group waitlist: 95% I2: $1993575 (695) intervention sessions plus CI: 7.68-24.27. I3: $1993651 (848) #2, 31 in twelve 90- control. minute Direct non- sessions of No difference healthcare costs in value of

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness

either: current health I1: $19932,316 (1) state between (3,691)

Cognitive/rel either 1 or 2 I2: $19931,544 axation and control (1,636)

program. after control I3: $19931,641 (2) Attention- completed (1,621) control of operant group rehabilitation. Indirect costs

discussion. I1: $19936,522 (17,387)

Control: I2: $19935,938 Waiting list (18,172)

for 8 weeks C: $19938,213 then operant (17,394) rehabilitation. No significant Measures: difference in costs. 3-year follow- up

Chronic Spine Pain For chronic spine pain, which includes back pain (not limited to the lower back) and neck pain, two studies of a brief cognitive behavioral physical therapy intervention versus traditional biomechanical physical therapy had conflicting cost-effective findings in the United Kingdom. While traditional physical therapy was more effective and more expensive than the brief cognitive behavioral intervention in both cases, only one study found that incremental cost- effectiveness of physical therapy versus brief cognitive behavioral therapy was within standard willingness to pay thresholds.

In the first study, traditional physical therapy cost an additional £68,000 per QALY as compared to brief cognitive behavioral therapy, which was outside typical willingness to pay thresholds. At the standard willingness to pay threshold of £20,000, there was 50% likelihood the brief intervention was more cost-effective; as the value decreased, the likelihood the brief intervention was cost-saving increased to almost 100%. Interestingly, these findings were sensitive to patient treatment preference and the researchers concluded that traditional physical therapy might be cost-effective for patients who do not have a treatment preference (Manca et al., 2006). In the second study, traditional physical therapy only cost £5,850 per additional QALY, well within standard willingness to pay thresholds. Moreover, traditional physical therapy also had greater patient satisfaction. The differences between the two studies may be explained, in part, by the fact that the first had a negligible difference in QALYs, while the second favored traditional physical therapy with higher QALYs. More studies will need to help clarify cost-effectiveness, potentially by factoring in patient preference and patient satisfaction (Manca et al., 2007; Moffett et al., 2006).

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Table 3. Behavioral Interventions for Chronic Spinal Pain Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Manca et al. 315 patients Intervention: Northwick PP: Societal (2007) & with (1) Brief Park Neck Moffett et al. musculoskelet cognitive Pain ICER (per (2006) al back or neck behavioral Questionnair QALY): pain for more physical e (NPQ): I2 vs. I1

Physical than 2 weeks therapy I1: 17.313 £2003-045,850 therapy for in UK. 154 in intervention I2: 18.100 back and intervention including neck pain in #1, 161 in identifying Roland Willingness to primary care intervention problems, Disability pay threshold: #2. developing Questionnair If value is solutions, e (RDQ): ≥£1K/QALY, and setting I1: 8.077 traditional goals. I2: 6.978 physical therapy (2) Tradition- has very high al physical Tampa Scale probability of therapy for being more cost- including Kinesiophobi effective than prescribed a (TSK): brief physical therapeutic Activity therapy pain exercises. avoidance management. subscale Measures: I1: 17.090 12 months I2: 16.495

Manca et al. 268 patients Interventions: Northwick PP: Societal (2006) with neck pain (1) Brief Park of physical Questionnair ICER (per Brief musculoskelet therapy e (NPQ): QALY): physical al origin for intervention I1: 10.5 (6.8) I2 vs. I1 therapy more than 2 based on I2: 8.6 (5.8) £2001-0268,000 intervention weeks in cognitive d: .302 versus usual community behavioral Willingness to physical settings in UK. principles for pay threshold: therapy 139 in 1 session and If value is management intervention up to 3 >£20K/QALY, for neck pain #1, 129 in sessions. Cost only 50% intervention £84/year. probability #2. (2) Usual traditional physical physical therapy therapy more cost- management. effective than Cost £152/ brief physical year. therapy intervention.

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Measures: For lower 12-month values, almost follow-up 100% probability brief physical therapy intervention is cost-saving.

Chronic Widespread Pain Two cost-effectiveness studies assessed telehealth interventions for non-specific widespread chronic pain, while another focused on group education for fibromyalgia. In a study in England and Scotland for patients with chronic widespread pain, a telephone-based Cognitive Behavioral Therapy (CBT) program was more cost-effective than a graded exercise program and than the both the telephone-based CBT and graded exercise programs combined. Additionally, compared to usual care, the telephone-based CBT program was the only intervention to fall within the standard willingness to pay threshold at £16,542 per QALY compared to £72,270 per QALY for the graded exercise program and £24,731 per QALY for the combined program. Notably, telephone- based CBT also had the highest likelihood of being a patient’s preferred option (McBeth et al., 2012).

In the Netherlands, an Internet-based CBT intervention for non-specific chronic pain was cost-saving at €40 saved per incremental improvement in a pain measure (Pain Catastrophizing Scale) over a face-to-face group CBT intervention after two months. The intervention was not compared to a physical intervention, usual care, or no intervention nor were its effects measured over a long duration. Nonetheless, in addition to being less expensive, the Internet-based version was also clinically more effective on multiple pain measures, with significant differences when limited to participants who completed the interventions (de Boer et al., 2014). Overall, the first study demonstrated the cost-effectiveness of a telehealth cognitive behavioral intervention compared to graded exercise and a combined program, and the second one confirmed a telehealth cognitive behavioral intervention could be more cost-effective than a face-to-face version, although longer studies are warranted.

For fibromyalgia, adding group discussion to group education appeared to be more cost-effective than adding group Cognitive Therapy after a year. Since both group discussion and group Cognitive Therapy included a psychologist, intervention costs were similar; however, group Cognitive Therapy had higher healthcare utilization costs. Since there were no significant differences in the number of days lost to absenteeism or quality of life, the lower costs of group discussion suggested it would be the more cost-effective option; however, it was not compared to group education alone (Goossens et al., 1996).

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Table 4. Behavioral Interventions for Chronic Widespread Pain Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness de Boer et al. 72 patients Interventions: Pain PP: Societal (2014) with non- Cognitive Catastrophizi specific behavioral ng Scale Total Costs (per Internet- chronic pain intervention (PCS): patient): based in the for 7 weeks I1: 11.00 I1: €1,745 cognitive Netherlands. plus 2-month (11.49) I2: €1,717 behavioral 22 completed booster: I2: 16.10 intervention intervention (1) Internet- (11.56) ICER (per 1- for non- #1, 28 based (p=.023) point specific completed intervention d: .443 improvement in chronic pain intervention with weekly PCS): #2. modules and Visual I1 vs. I2 homework Analogue -€40 plus email Scale: contact with Pain severity therapist. I1: 5.19 (2.53) (2) Face-to- I2: 5.49 (2.32) face cognitive (p=.020) behavioral d: .124 group (5-8 people) Interference intervention I1: 5.13 (2.52) with weekly I2: 6.33 (2.21) 2-hour d: .507 sessions. Fatigue Measures: I1: 5.91 (2.44) 2-month I2: 6.88 (2.32) follow-up d: .408 McBeth et al. 390 patients Interventions: Percent PP: Healthcare (2012) with chronic (1) Significant widespread Telephone- Improvement ICER (per Cognitive pain for more based in Global QALY):

Behavioral than 3 months Cognitive Change in I1: £2009-1016,542 Therapy, in England Behavioral Health: I2: £2009-1072,270 exercise, or and Scotland. Therapy with I1: 32.6% I3: £2009-1024,731 both for 91 in 7 weekly 45- I2: 24.2% chronic intervention 60-minute I3: 37.1% Willingness to widespread #1, 99 in sessions, one C: 8.3% pay threshold: pain intervention 3-month Telephone- #2, 102 in session, one Global Health delivered intervention 6-month Questionnair Cognitive #3, 98 in session. e (GHQ): Behavioral control. (2) Graded I1: 2.0 (3.6) Therapy had the exercise with I2: 2.0 (3.0) highest

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness gym-based I3: 2.0 (3.4) probability exercise C: 3.0 (3.8) (70%) of being program and more cost- 6 monthly d1: .270 effective than sessions. d2: .294 treatment as (3) Both I1 d3: .278 usual. and I2 combined.

Control: Treatment as usual.

Measures: 9 months Goossens et 131 patients Interventions: Days of Pain- PP: Societal al. (1996) with Group Related fibromyalgia education +: Absence from Total Direct Cognitive (mean (1) Group Work: Costs (per educational duration of 10 cognitive I1: 42 (82) patient-year): treatment of years). 88% therapy. I2: 50 (56) I1: $4,260 (6510) fibromyalgia female. 49 in Approx. (NS) I2: $2,637 (4649) intervention $980/patient (p=.001) #1, 39 in (2) Group d: .116 intervention discussion. #2, 43 in Approx. Days of control. $980/patient. Inability to Perform Control: Daily Waiting list Activities: for 6 weeks. I1: 34 (71) I2: 44 (55) Measures: (NS) 1-year follow- up d: .159

Return to Work While also concerned with managing pain symptoms, return-to-work programs specifically target pain-related workplace absenteeism. Oftentimes, these interventions occur in part or whole at the workplace rather than a healthcare setting.

Prevention Interventions For persons with acute low back pain at risk for chronic pain, a functional restoration early intervention including psychosocial and physical reconditioning and coping skills training that incorporated psychology, physical

372 Chronic Pain therapy, occupational therapy, and case management had the potential to be more cost-effective than no intervention, particularly for high-risk patients. The functional restoration intervention led to a significantly higher rate of return to work (90%) than no intervention (69% of high-risk patients; 87% of low-risk patients) and had significantly lower total costs ($12,721 versus $21,843) after a year (Gatchel et al., 2003).

Table 5. Prevention Interventions for Work-Absenteeism Due to Chronic Pain Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Gatchel et al. 124 patients Intervention: Percent PP: Societal (2003) with acute low Early Return to back pain, 70 functional Work: Early high-risk (HR) restoration I: 91% Total Costs (per intervention and 54 low- intervention C-HR: 69% patient): for acute low risk (LR) for with psychol- C-LR: 87% I: $12,721 back pain to developing ogy, physical C-HR: $21,843 prevent chronicity. therapy, Number of (p<.05) progression Within high- occupational Disability to chronic risk, 22 in therapy, and Days Due to pain intervention, case manage- Back Pain: 48 in control. ment for I: 38.2 individual C-HR: 102.4 psychosocial C-LR: 20.8 and physical conditioning Self-Rated and coping Pain (last 3 skills training months): over 3 weeks. I: 26.8 Average cost C-HR: 43.1 $3885/patient C-LR: 25.7 Control: No intervention Measures: 1-year follow- up

Treatment Interventions Chronic Low Back Pain Three studies from the Netherlands assessed return-to-work programs for employees who took sick leave due to sub-acute or chronic low back pain. First, an integrated care program including a workplace intervention and cognitive behavioral graded activity program dominated usual care at all willingness to pay thresholds after a year, saving £61,000 per QALY. Additionally, it only cost £3 per one day earlier return to work. If the value were £10 per one day earlier return to work, the intervention had 95% likelihood of being more cost-effective for reducing workplace absenteeism as well (Lambeek et al., 2010).

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A similar study, which did not conduct a formal cost-effectiveness analysis, also suggested a cognitive behavioral graded activity program may be more cost- effective than usual care at reducing workplace absenteeism after a year. While healthcare utilization costs were non-significantly lower in the cognitive behavioral program (€83), the main cost contributor was productivity losses, with both gross losses (i.e. total number of days the workers were completely or partially sick-listed) and net losses (i.e. percentage of work absence) lower in the cognitive behavioral program (€3,655 gross and €999 net). After three years, the patterns of lower costs persisted but were no longer significant; however, there was a potential cumulative savings of €1,661 per worker (Hlobil et al., 2007; Staal et al., 2004).

The third study took a stepped care approach: First, participants received either a workplace intervention with workplace assessment, work modifications, and case management or usual care with an occupational physician. After eight weeks, 43% returned to work. Then, the remaining 57% were assigned to a clinical intervention with operant-based graded activity physical therapy or usual care. Overall, there were six conditions: (1) workplace intervention for eight weeks, (2) usual care for eight weeks, (3) workplace intervention plus subsequent usual care, (4) workplace intervention plus subsequent clinical intervention, (5) usual care plus subsequent clinical intervention, and (6) usual care plus subsequent usual care. After 52 weeks, 88% had returned to work. In the first step, the workplace intervention appeared cost-effective over usual care with no differences in costs and an average of 30 days earlier return to work, which cost €19 per day earlier return to work. However, in the second step, the clinical intervention was dominated by usual care with higher costs and worse outcomes, including a delay in return work (21.3 days later than usual care and 50.9 days later than combined workplace and clinical interventions). In other words, the workplace intervention alone and in combination with the clinical intervention may be cost-effective options, but the clinical intervention following usual care is not (Steenstra et al., 2006).

Table 6. Behavioral Interventions for Work-Absenteeism Due to Chronic Low Back Pain Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Lambeek et 117 sick-listed Intervention: Duration PP: Societal al. (2010) workers (age Integrated Until Lasting 18 to 65 years) care with Return to ICER (per Integrated with chronic workplace Work (i.e. QALY): care for low back pain intervention days from first -£61,000 patients with in the and cognitive day of sick- chronic low Netherlands. behavioral leave to full ICER (per one back pain 58 in graded return to work day earlier intervention, activity for at least 4 return to work): 59 in control. program. weeks): £3 I: 129 (117) Control: C: 197 (129) Willingness to Usual care. pay threshold:

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness d: .553 Regardless of Measures: value per 12 months QALY, integrated care with workplace intervention and graded activity more cost- effective than usual care. If value is £10 per one day earlier return to work, 95% probability integrated care more cost- effective. Hlobil et al. 129 sick-listed Intervention: Mean PP: Employer (2007) & workers with Graded Difference of Staal et al. non-specific activity with Net Lost Healthcare (2004) low back pain 60-minute Productivity Costs: for more than cognitive Days: 12 months

Graded 4 weeks in a behavioral First year I: €1999800 (680) activity company in physical 9.1 (95% CI, C: €1999716 intervention the exercise -14.8 to 31.5) (1,096) for workers Netherlands. session with non- 94% male. 65 2x/week Second year Mean Difference specific sub- in until return -1.1 (95% CI, Net Lost acute low intervention, to work or 3 -24.6 to 24.5) Productivity back pain 64 in control. months. Costs: Average cost Third year First year

€475/patient. 2.8 (95% CI, €1999999 (95% CI, -15.6 to 20.7) -1,073 to 3,115) Control: Usual care Cumulative Second year

with routine 12.0 (95% CI, €1999118 (95% CI, guidance -50.2 to 64.9) -2,079 to 2,541) from occupational Mean Third year

physician. Difference of €1999467 (95% CI, Gross Lost -1,173 to 2,207) Measures: Productivity 1-year follow- Days: Cumulative

up & 3-year First year €19991,661 (95% follow-up 40.4 (95% CI, CI, -4,154 to 4.7 to 78.8) 6,913)

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Second year 12.1 (95% CI, Mean Difference -27.6 to 49.7) of Gross Lost Productivity Third year Costs: 13.3 (95% CI, First year

-24.7 to 50.1) €19993,655 (95% CI, 157 to 6,933) Cumulative 79.2 (95% CI, Second year

-23.8 to 192.3) €19991,522 (95% CI, -2,315 to 5,126)

Third year

€19991,685 (95% CI, -1,673 to 5,623)

Cumulative

€19997,581 (95% CI, -3,262 to 17,348) Steenstra et 196 workers Interventions: Mean PP: Societal al. (2006) (age 18-65 (1) Work- Improvement years) on sick place inter- s in Lasting Total Costs: Stepped care leave for 2-6 vention with Return to I1: €8,993 (6,216) return-to- weeks due to workplace Work (i.e. C: €9,109 (6,375) work low back pain assessment, days from first I1+C: €11,096 program for in the work modific day of sick- (6,720) workers with Netherlands. ations and leave to full I1+I2: €12,391 low back 96 in case manage- return to work (7,383) pain intervention ment 2-8 for at least 4 C+I2: €10,537 #1, 100 in weeks after weeks): (3,601) usual care. sick leave. I1: 100.14 C+C: €10,885 After 8 weeks, (2) Clinical (96.38) (7,363) subset returns intervention C: 130.12 to work (41 in with operant I1+C: 109.88 ICER (per intervention graded (62.55) QALY): #1, 43 in activity I1+I2: 160.78 I1 vs. C control). physical (78.66) −€1,483 Remainder therapy 8 C+I2: 172.75 randomized weeks after (85.87) I1+I2 vs. I1+C again: 55 in sick leave. C+C: 151.41 €24,416 intervention (3) Combined (105.11) #2, 57 in I1 and I2. C+I2 vs. C+C

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness control. Mean €5,447 Control: Improvement Usual care s in ICER (per one from Functional day earlier occupational Status: return-to-work): physician. I1: −7.84 I1 vs. C (5.69) €19 Measures: C: −8.75 52 weeks (6.29) I1+I2 vs. I1+C after first day I1+C: −10.08 €11 of sick leave (5.77) I1+I2: −8.29 C+I2 vs. C+C (6.98) €29 C+I2: −6.12 (4.62) C+C: −9.18 (6.87)

Mean Im- provements in Pain Severity: I1: −2.45(2.65) C: −2.65(2.69) I1+C: −2.79 (2.98) I1+I2: −2.41 (2.39) C+I2: −2.07 (2.32) C+C: −3.06 (3.15)

Sick Leave (Net days): I1: 77.3 (53.9) CI: 93.1 (68.8) I1+C: 85.9 (51.5) I1+I2: 122.0(74.5) C+I2: 110.4 (55.3) C+C: 102.4 (71.5)

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Chronic Spine Pain For employees in Sweden who took sick leave due to chronic pain, a multidisciplinary rehabilitation program for back and neck pain included weekly group sessions, worksite visits, and booster sessions. In addition to the multidisciplinary rehabilitation program, one study arm also included behavior- oriented physical therapy with a tailored exercise training program, a second study arm also included Cognitive Behavioral Therapy (CBT), and a third study arm included both physical therapy and CBT. After three years, there were no significant differences in workplace absenteeism or costs except for the subset of women in the combined intervention. No formal cost-effectiveness analysis was conducted, but the researchers concluded behavior-oriented physical therapy and CBT combined was more cost-effective than either physical therapy or CBT alone at improving health and decreasing costs for women suffering from chronic spinal pain (Jensen et al., 2005).

Table 7. Behavioral Interventions for Work-Absenteeism Due to Chronic Spinal Pain Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Jensen et al. 186 workers Interventions: Total PP: Societal (2005) on sick-leave Multidiscipli Absences across nary rehabil- Post- Total Costs: Intensive Sweden. 49 in itation with 6 Intervention: Females multidiscipli intervention group (4-8 Females I1: €189,760 nary #1, 48 in people) ses- I1: 522 (386) I2: €157,800 rehabilitatio intervention sions over 4 I2: 542 (446) I3: €107,703 n program #2, 41 in weeks and 6 I3: 439 (329) C: €245,212 for back and intervention booster C: 572 (424) neck pain #3, 48 in sessions over Males control. next year: d1: .123 I1: €220,268 (1) Individ- d2: .069 I2: €199,824 ually tailored d3: .353 I3: €130,015 behavior- C: €193,239 oriented Males physical ther- I1: 541 (446) Combined apy program I2: 629 (379) intervention for ~20 I3: 494 (375) effective in hours/week. C: 479 (408) improving health (2) Cognitive and decreasing behavioral d1: .145 costs for women therapy for d2: .381 suffering from ~13-14 d3: .038 spinal pain. hours/week. (3) Both I1 Only and I2. significant difference in Control: sick leave was Treatment as for females in usual. combined

378 Chronic Pain

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Measures: intervention. 3-year follow- up

Musculoskeletal Disorders In Spain, adding an early cognitive behavioral treatment to a rheumatologic care program for treating musculoskeletal disorders, was found to be cost-saving at $1,796 per person saved over the rheumatologic care program alone for persons with recent-onset temporary work disability due to musculoskeletal disorders. Specifically, the cognitive behavioral treatment included weekly sessions until the person returned to work, which added more than 20% efficacy to the rheumatologic care program and reduced duration of relapses at the cost of $13.50 per one less day of temporary work disability after two years (Leon et al., 2009).

Table 8. Behavioral Interventions for Work-Absenteeism Due to Musculoskeletal Disorders Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Leon et al. 181 patients Intervention: Days of work PP: Societal (2009) with recent- Rheumatolog disability per Total Costs (per onset ic care 100 patients: person): Early temporary program plus I: 12,008 I vs. C cognitive- work weekly, C: 15,671 -$20071,796 behavioral disability individual treatment for for ≥4 weeks cognitive- Mean ICER (per 1 less patients with caused by behavioral Duration of day of TWD): work musculoskelet treatment, TWD $200713.50 disability al disorders in with number Episodes in due to Spain. 77.3% of sessions Days: Cost-Benefit musculoskel female. 115 in dependent on I: 97.9 (102) (saving per etal intervention, patient’s C: 127 (116) dollar invested): disorders 66 in control. return to (p=.053) $20074.08 work. d: .267 Net Benefit:

Control: Adds >20% $2007172,607 Rheumatolog efficacy to the ic care rheumatologic program care program, only. and reduces the duration of Measures: relapses. 24 months

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Surgery and Post-Surgical Pain Few studies compare surgical and non-surgical options. For patients in Norway with chronic low back pain due to degenerative disc disease, total disc replacement surgery appeared to be more cost-effective than multidisciplinary rehabilitation after two years, with much greater clinical and quality of life gains despite being more expensive. The surgical intervention cost €39,748 per QALY, which had 90% likelihood of being cost-effective at Norway’s standard willingness to pay threshold; however it is worth noting that based on a different measure of quality of life (SF-6D instead of EQ-5D), it cost €128,328 per QALY, which would not be within the threshold (Johnsen et al., 2014; Hellum et al., 2011).

Meanwhile, for post-surgical patients experiencing pain that impedes functioning after first-time lumbar disc surgery, a behavioral graded activity program with increasing intensity and positive reinforcement appeared less cost- effective than traditional physical therapy after a year, with no clinical differences in recovery, disability, or pain severity and higher direct and indirect costs (Ostelo et al., 2004). Notably, lumbar disc surgery can be recommended for chronic pain.

Table 9. Behavioral Interventions versus Surgery or for Post-Surgical Pain Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Johnsen et al. 144 patients Interventions: Oswestry PP: Societal (2014) & with chronic (1) Multi- Disability Hellum et al. low back pain disciplinary Index (ODI): ICER (per (2011) for more than rehabilitation First year QALY): one year and emphasizing I1: 33.0 (16.6) I2 vs. I1 Total disc degenerative exercises and I2: 22.3 (17.0) €39,748 to replacement changes in cognitive (p<.001) €128,328 versus lumbosacral intervention multidiscipli intervertebral for ~60 hours d: .636 Willingness to nary discs in over 3-5 pay threshold: rehabilitatio Norway. 68 in weeks. Second year For lower n in patients intervention Estimated I1: 30.0 (16.0) estimate, if with chronic #1, 74 in cost €5,977/ I2: 21.2 (17.1) value is low back intervention patient. (p=.001) €74,600/QALY, pain #2. (2) Total disc 90% probability replacement d: .532 total disc in the lumbar replacement spine. more cost- Estimated effective than cost €10,846/ multidisciplinar patient. y rehabilitation.

Measures: 2-year follow- up

380 Chronic Pain

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Ostelo et al. 105 patients Intervention: Percent PP: Societal (2004) (age 18-65 Behavioral Recovered years) graded ac- Patients: Total Costs: Behavioral- following tivity pro- I: 75% Direct graded first-time gram of C: 73% I: €19971,978 activity lumbar disc increasing (1894) program vs. surgery with intensity and Roland C: €19971,339 physical complaints positive rein- Disability (1,873) therapy after (e.g., pain) forcement to Questionnair lumbar disc restricting increase e (RDQ): Indirect – absence surgery their activities health be- I: 7.0 (5.5) from labor

of daily living haviors and C: 7.0 (5.3) I: €19975,774 or work in the decrease pain (8,880)

Netherlands. behaviors for d: 0 C: €19972,347 52 in eighteen 30- (6,064) intervention, minute Main 53 in control. sessions over Complaint: Indirect – unpaid 3 months. I: 50.3 (27.4) labor

C: 44.3 (30.6) I: €19971,421 Control: (2,804)

Usual care d: .207 C: €1997407 from physical (1,386) therapist for Severity of eighteen 30- Back Pain: Behavioral graded minute I: 17.6 (32.5) activity program sessions over C: 22.4 (33.6) associated with 3 months. higher direct and d: .145 indirect costs. Measures: 12-month No clinical follow-up differences.

LIMITATIONS AND FUTURE DIRECTIONS There is a surprising dearth of cost-effectiveness studies for chronic pain management in the U.S. population, which limits generalizability of findings thus far. Ones of the biggest limitations is the condition itself: the subjective experience of pain is influenced by physiological, psychological, and social factors; there are a range of potential physical causes (e.g. injury, infection) as well as changes to neural circuits that are currently undetectable with standard medical tests; the pain can persist with intense severity over long durations; it can have a debilitating impact on life and workplace functioning; there are a lack of treatments that can eliminate pain completely; and patients with similar conditions may respond to different treatment interventions.

Regardless of the cause of pain, the experience of pain over time will shape thought, emotion, and behavior patterns. Immediate worsening of pain will tend

381 Chronic Pain to encourage avoidance of contexts and behaviors that preceded the increase in pain; immediate relief from pain will tend to encourage repetition of thoughts, feelings and behaviors that preceded the immediate relief. Without attention, this reward learning process can lead to the development of habits that maintain pain and disability, and increase the frequency of negative thoughts and affect. For example, persons in chronic pain may learn to avoid exercise, activities or work that would make them better in the long-term, but increase pain initially, or they may learn to use substances (e.g. alcohol) to cope, which provide immediate relief but worsen affect with repeated use. Cognitive, behavioral, graded activity, and physical therapy interventions intentionally

In particular, the inability to eliminate pain completely requires a deeper understanding of the psychosocial factors that influence the perception and perpetuation of pain, and may limit positive behaviors and reinforce negative behaviors that become associated with immediate worsening or relief (e.g., exercise or drinking alcohol).

Ultimately, understanding the underlying mechanisms of chronic pain will allow for more targeted interventions, as well as improved tailoring of existing interventions. We know opioid therapy is a non-optimal solution for intractable cases, given the high potential for misuse or abuse. Developing or identifying alternative treatments remains critical. Longer studies and those that incorporate a societal perspective will be able to demonstrate even stronger cost-effectiveness for the costs saved from pain management if clinical effects persist over time. Chronic pain remains one of the most common reasons to seek out healthcare and to miss or function sub-optimally at work, contributing to a high economic burden. Cost-effective solutions for pain management are vital.

KEY POINTS • Cost-effectiveness studies of behavioral interventions for chronic pain broadly focus on improving pain management and/or accelerating return-to- work, with most currently available studies from outside the United States.

Temporomandibular Pain • For prevention in patients with acute jaw and face pain at high risk for chronic pain, a biopsychosocial intervention including cognitive behavioral skills training and biofeedback was more cost-effective than usual care after a year, with bigger clinical improvements and lower healthcare costs per person.

Chronic Low Back Pain • For prevention in patients with acute low back pain at risk for chronic pain, a functional restoration early intervention including psychosocial and physical reconditioning and coping skills training had the potential to be more cost- effective than no intervention after a year, particularly for high-risk patients, with greater clinical improvements and almost half of the societal costs.

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• Adding a cognitive behavioral intervention including a group exercise program to an educational book and audiocassette was more cost-effective than the educational book and audiocassette alone per QALY after a year. • Adding a cognitive behavioral intervention to active management was more cost-effective than active management alone per QALY after a year; however, the cognitive behavioral intervention was dominated when limited to persons with low pain intensity, suggesting it may only be cost-effective for persons with moderate and/or high pain intensity. • Adding a cognitive behavioral intervention to inpatient rehabilitation was cost-saving over inpatient rehabilitation alone at €126,731 saved per QALY after six months. These cost differences were driven by differences in days off from work and not improvements in pain or discomfort symptoms. • Adding a cognitive behavioral intervention to operant treatment was equally cost-effective as adding a group discussion with no differences in clinical effects or costs after three years; however, no comparison was made to operant treatment alone. • A cognitive behavioral graded activity program appeared more cost-effective than usual care with significantly lower productivity losses after one year and non-significant patterns in the same direction after three years. • A behavioral intervention of graded activity and problem-solving was more cost-effective than a physical intervention of aerobics and strength and endurance at all willingness to pay thresholds after six months, and cost- saving over both the behavioral and physical interventions combined at €108,857 saved per QALY. • Physical therapy was more cost-effective than advice about physical therapy at £3,010 per QALY after a year, with the probability never exceeding 73%. • A workplace intervention plus cognitive behavioral graded activity program dominated usual care as cost-saving at £61,000 per QALY after a year and only cost £3 per day earlier return to work. • A workplace intervention of assessment, work modifications, and case management could be cost-effective than usual care at €19 per day earlier return to work. For those who did not recover in the first eight weeks, a clinical intervention with operant-based graded activity physical therapy was dominated by usual care as less clinically effective and more expensive.

Chronic Spinal Pain • Across two studies, a brief cognitive behavioral physical therapy program was less effective and less expensive than traditional physical therapy after a year; in one study, traditional physical therapy cost £5,850 per QALY and in the other £68,000 per QALY. • A multidisciplinary rehabilitation program with a tailored exercise training program, Cognitive Behavioral Therapy (CBT), or both combined, only appeared to be have significantly improved outcomes and decreased costs for the subset of women in the combined intervention after three years.

383 Chronic Pain

Chronic Widespread Pain • Telephone-based Cognitive Behavioral Therapy (CBT) was more cost- effective than graded exercise or both CBT and graded exercise combined after nine months, and was the only one within a standard willingness to pay threshold compared to treatment at usual at £16,542 per QALY. • Internet-based Cognitive Behavioral Therapy (CBT) was cost-saving over in- person group CBT at €40 saved per incremental improvement in a pain measure after two months. • For fibromyalgia, adding group discussion appeared more cost-effective than adding Cognitive Therapy to group education after a year since there were no clinical differences but group discussion had lower healthcare costs.

Musculoskeletal Disorders • For musculoskeletal disorders, adding cognitive behavioral treatment to rheumatologic care was cost-saving compared to rheumatologic care alone after two years, only costing $13.50 per one less day of temporary work disability.

Surgery and Post-Surgical Pain • For chronic low back pain due to degenerative disc disease, total disc replacement surgery appeared more cost-effective than multidisciplinary rehabilitation at €39,748 per QALY after two years, with 90% probability of cost-effectiveness at a standard willingness to pay threshold. • For pain after first-time lumbar disc surgery, a behavioral graded activity program appeared less cost-effective than traditional physical therapy with no clinical differences and higher direct and indirect costs after a year.

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Frost H, Lamb SE, Doll HA, Carver PT, Stewart-Brown S. Randomised controlled trial of physiotherapy compared with advice for low back pain. BMJ. 2004 Sep 25;329(7468):708.

Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012 Aug;13(8):715-24.

Gatchel RJ, Peng YB. Biopsychosocial management of chronic pain. In Trafton JA & Gordon WP (Eds.), Best Practices in the Behavioral Management of Chronic Disease, Volume I. Los Altos: Institute for Brain Potential, 2012.

Gatchel RJ, Polatin PB, Noe C, Gardea M, Pulliam C, Thompson J. Treatment- and cost-effectiveness of early intervention for acute low-back pain patients: a one-year prospective study. J Occup Rehabil. 2003 Mar;13(1):1-9.

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Goossens ME, Rutten-Van Mölken MP, Kole-Snijders AM, Vlaeyen JW, Van Breukelen G, Leidl R. Health economic assessment of behavioural rehabilitation in chronic low back pain: a randomised clinical trial. Health Econ. 1998 Feb;7(1):39-51.

Goossens ME, Rutten-van Mölken MP, Leidl RM, Bos SG, Vlaeyen JW, Teeken- Gruben NJ. Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. II. Economic evaluation. J Rheumatol. 1996 Jul;23(7):1246-54.

Hardt J, Jacobsen C, Goldberg J, Nickel R, Buchwald D. Prevalence of chronic pain in a representative sample in the United States. Pain Med. 2008 Oct;9(7):803- 12.

Hellum C, Johnsen LG, Storheim K, Nygaard OP, Brox JI, Rossvoll I, Rø M, Sandvik L, Grundnes O; Norwegian Spine Study Group. Surgery with disc prosthesis versus rehabilitation in patients with low back pain and degenerative disc: twoyear follow-up of randomised study. BMJ. 2011 May 19;342:d2786.

Hlobil H, Uegaki K, Staal JB, de Bruyne MC, Smid T, van Mechelen W. Substantial sick-leave costs savings due to a graded activity intervention for workers with non-specific sub-acute low back pain. Eur Spine J. 2007 Jul;16(7):919-24.

Jensen IB, Bergström G, Ljungquist T, Bodin L. A 3-year follow-up of a multidisciplinary rehabilitation programme for back and neck pain. Pain. 2005 Jun;115(3):273-83.

Johannes CB, Le TK, Zhou X, Johnston JA, Dworkin RH. The prevalence of chronic pain in United States adults: results of an Internet-based survey. J Pain. 2010 Nov;11(11):1230-9.

Johnsen LG, Hellum C, Storheim K, Nygaard ØP, Brox JI, Rossvoll I, Rø M, Andresen H, Lydersen S, Grundnes O, Pedersen M, Leivseth G, Olafsson G, Borgström F, Fritzell P; Norwegian Spine Study Group. Cost-effectiveness of total disc replacement versus multidisciplinary rehabilitation in patients with chronic low back pain: a Norwegian multicenter RCT. Spine (Phila Pa 1976). 2014 Jan 1;39(1):23-32.

Johnson RE, Jones GT, Wiles NJ, Chaddock C, Potter RG, Roberts C, Symmons DP, Watson PJ, Torgerson DJ, Macfarlane GJ. Active exercise, education, and cognitive behavioral therapy for persistent disabling low back pain: a randomized controlled trial. Spine (Phila Pa 1976). 2007 Jul 1;32(15):1578-85.

Kole-Snijders AM, Vlaeyen JW, Goossens ME, Rutten-van Mölken MP, Heuts PH, van Breukelen G, van Eek H. Chronic low-back pain: what does cognitive coping skills training add to operant behavioral treatment? Results of a randomized clinical trial. J Consult Clin Psychol. 1999 Dec;67(6):931-44.

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Lamb SE, Lall R, Hansen Z, Castelnuovo E, Withers EJ, Nichols V, Griffiths F, Potter R, Szczepura A, Underwood M; BeST trial group. A multicentred randomised controlled trial of a primary care-based cognitive behavioural programme for low back pain. The Back Skills Training (BeST) trial. Health Technol Assess. 2010 Aug;14(41):1-253, iii-iv.

Lambeek LC, Bosmans JE, Van Royen BJ, Van Tulder MW, Van Mechelen W, Anema JR. Effect of integrated care for sick listed patients with chronic low back pain: economic evaluation alongside a randomised controlled trial. BMJ. 2010 Nov 30;341:c6414.

Leon L, Jover JA, Candelas G, Lajas C, Vadillo C, Blanco M, Loza E, Perez MA, Redondo M, Abasolo L. Effectiveness of an early cognitive-behavioral treatment in patients with work disability due to musculoskeletal disorders. Arthritis Rheum. 2009 Jul 15;61(7):996-1003.

Manca A, Dumville JC, Torgerson DJ, Klaber Moffett JA, Mooney MP, Jackson DA, Eaton S. Randomized trial of two physiotherapy interventions for primary care back and neck pain patients: cost effectiveness analysis. Rheumatology (Oxford). 2007 Sep;46(9):1495-501.

Manca A, Epstein DM, Torgerson DJ, Klaber Moffett JA, Coulton S, Farrin AJ, Hahn S, Jackson DA, Richmond SJ. Randomized trial of a brief physiotherapy intervention compared with usual physiotherapy for neck pain patients: cost- effectiveness analysis. Int J Technol Assess Health Care. 2006 Winter;22(1):67-75.

McBeth J, Prescott G, Scotland G, Lovell K, Keeley P, Hannaford P, McNamee P, Symmons DP, Woby S, Gkazinou C, Beasley M, Macfarlane GJ. Cognitive behavior therapy, exercise, or both for treating chronic widespread pain. Arch Intern Med. 2012 Jan 9;172(1):48-57.

Moffett JK, Jackson DA, Gardiner ED, Torgerson DJ, Coulton S, Eaton S, Mooney MP, Pickering C, Green AJ, Walker LG, May S, Young S. Randomized trial of two physiotherapy interventions for primary care neck and back pain patients: ‘McKenzie' vs brief physiotherapy pain management. Rheumatology (Oxford). 2006 Dec;45(12):1514-21.

Ostelo RW, Goossens ME, de Vet HC, van den Brandt PA. Economic evaluation of a behavioral-graded activity program compared to physical therapy for patients following lumbar disc surgery. Spine (Phila Pa 1976). 2004 Mar 15;29(6):615-22.

Pai S, Sundaram LJ. Low back pain: an economic assessment in the United States. Orthop Clin North Am. 2004 Jan;35(1):1-5.

Rivero-Arias O, Gray A, Frost H, Lamb SE, Stewart-Brown S. Cost-utility analysis of physiotherapy treatment compared with physiotherapy advice in low back pain. Spine (Phila Pa 1976). 2006 May 20;31(12):1381-7.

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Schweikert B, Jacobi E, Seitz R, Cziske R, Ehlert A, Knab J, Leidl R. Effectiveness and cost-effectiveness of adding a cognitive behavioral treatment to the rehabilitation of chronic low back pain. J Rheumatol. 2006 Dec;33(12):2519-26.

Smeets RJ, Severens JL, Beelen S, Vlaeyen JW, Knottnerus JA. More is not always better: cost-effectiveness analysis of combined, single behavioral and single physical rehabilitation programs for chronic low back pain. Eur J Pain. 2009 Jan;13(1):71-81.

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Stowell AW, Gatchel RJ, Wildenstein L. Cost-effectiveness of treatments for temporomandibular disorders: biopsychosocial intervention versus treatment as usual. J Am Dent Assoc. 2007 Feb;138(2):202-8.

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387 Dementia

CHAPTER 17: DEMENTIA

ABSTRACT Dementia refers to global cognitive decline with multiple cognitive impairments such as in memory, language, focus, planning, reasoning, coordination, and/or perception that interfere with daily functioning. It can also be accompanied by behavioral and psychological changes such as paranoia, agitation, aggression, and depression.

Dementia is most often caused by neurodegenerative disorders (e.g., Alzheimer's Disease) in older age. Much of the care for dementia occurs in the home, which exerts a physical, emotional, and financial toll on these informal caregivers and can negatively impact the caregiver’s own mental and physical health. In the United States, prevalence of dementia in people over the age of 70 years was estimated at 13.7%, costing $159 to $215 billion in direct and indirect costs annually.

Only a few cost-effectiveness studies are available, with most studies from outside the United States. For persons with dementia, Cognitive Stimulation Thera- py (CST), combining Reality Orientation and Reminiscence Therapy, may be more cost-effective than usual care at improving cognitive function and dementia-related quality of life, depending on willingness to pay thresholds; however, continuing CST beyond its standard duration was less cost-effective than returning to usual care. For caregivers of persons with dementia, a home-based behavioral intervention to decrease caregiver stress and improve patient management only cost $5 per day to decrease caregiving by one hour, but did not assess cost- effectiveness for health or quality of life outcomes. A coping strategy intervention at the caregiver's preferred location was more cost-effective than no intervention in terms of quality of life and may be cost-effective in terms of mental health, depending on the willingness to pay threshold. However, neither a structured family intervention nor a structured befriending intervention was cost- effective compared to usual care. For caregivers and patients together, joint reminiscence groups were less cost-effective than usual care but occupational therapy was cost-saving over usual care. Overall, more data are needed before any meaningful conclusions can be reached for the most cost-effective interventions for both persons with dementia and their caregivers.

BACKGROUND ON DEMENTIA Dementia is often used as an umbrella term for global cognitive decline, but it is officially a syndrome comprised of multiple cognitive deficits such as impairments in memory, language and communication, focus and attention, planning and organizing, reasoning and judgment, motor coordination, and visual perception that interfere with daily functioning.

In addition to these cognitive deficits, behavioral and psychological changes can also cause significant impairments. These include inappropriate behaviors like agitation, aggression (e.g., hitting, screaming), wandering, or repetitive question- ing; psychological factors like delusions, depression, or anxiety; as well as personality changes. Generally, all dementia symptoms worsen over time.

388 Dementia

Age and genetics both contribute to risk for dementia, which is typically caused by progressive neurodegenerative disorders like Alzheimer’s Disease (the leading cause of dementia) and Vascular Dementia (common after strokes). Since neurodegenerative disorders lead to differing patterns of brain damage, symptoms can vary correspondingly. In some cases, dementia can be induced or simu- lated by reversible causes like medication, depression, nutritional deficiencies, or metabolic/endocrine disorders (e.g., hypothyroidism), but these types of demen- tias are not included here.

Caregivers of Persons with Dementia A significant portion of care for dementia occurs informally by family members (e.g., spouses, children) or friends at home rather than within the healthcare system. This caregiving is often physically, emotionally, and financially burdensome on the caregiver, and is considered a risk factor for problems with the caregiver’s own mental and physical health. A growing body of research is assessing the impact of informal caregiving for dementia and developing interventions to improve caregiver outcomes as well as decrease associated costs.

PREVALENCE OF DEMENTIA In the United States, prevalence of dementia in those over the age of 70 years was estimated at 13.7% or 3.3 million people as of 2010. Of that number, almost 70% was due to Alzheimer’s Disease at 9.5% or 2.3 million people (Brookmeyer et al., 2011). Another estimate specific to Alzheimer’s Disease in those over the age of 65 years was 4.7 million people as of 2010 This was estimated to increase to 13.8 million people by 2050 (Herbert et al., 2013). As older adults comprise a growing proportion of the U.S. population, prevalence of dementia will continue to rise.

ECONOMIC BURDEN OF DEMENTIA The annual economic burden of dementia in the United States was estimated at $109 billion for direct healthcare costs alone and $159 to $215 billion including indirect costs (e.g., unpaid caregiving) as of 2010. The researchers noted that direct healthcare costs for dementia were higher than those for heart disease ($102 billion) and cancer ($77 billion). Notably, 75% to 84% of dementia-related costs are due to care (e.g., nursing home care, formal home care, informal home care), which may differ from other disorders. As the number of older adults increases, the overall economic burden of dementia is estimated to more than double by 2040, with one estimate of annual costs exceeding $350 billion by 2050 (Hurd et al. 2013; Nichols et al., 2008).

CLINICALLY EFFECTIVE INTERVENTIONS There are no cures for neurodegenerative causes of dementia, and limited evidence-based options to delay progression or manage symptoms.

Pharmacological options approved by the Federal Drug Administration include cholinesterase inhibitors (e.g., donepezil, galantamine, rivastigmine, tacrine) and a neuropeptide-modifying agent (memantine), but evidence for clinically meaningful improvements in cognitive function is variable and modest (Qaseem et al., 2008). Psychotropic medication may be recommended for behavioral and psychological factors including psychosis, agitation, depression, and apathy; howev-

389 Dementia er, the significant risks of adverse events with psychotropic use in the elderly need be considered in risk benefit assessments prior to prescribing them.

No psychosocial interventions have a strong evidence base at this time. Trials of psychosocial interventions have demonstrated mixed efficacy for specific behavioral issues but no consistent global benefits. Tested interventions included Reali- ty Orientation and Reminiscence Therapy. Reality Orientation targets cognitive function by utilizing orientating information like time and location. Reminis- cence Therapy aims to stimulate memory and improve mood through discussion of the patient’s life history, which can have small short-term benefits in cognition, behavior, and mood. Cognitive Stimulation Therapy combines Reality Orienta- tion and Reminiscence Therapy into a single treatment. Other stimulation interventions have mixed efficacy, including sensory stimulation (e.g., aromatherapy), recreational activities (e.g., crafts, games), and art therapies (e.g., music, dance).

Caregivers of Persons with Dementia Psychosocial interventions to improve the health and quality of life for caregivers of people with dementia are also needed. Common interventions include Psy- choeducation, Support Groups, and Problem-Solving Skills focused on coping, managing stress, and increasing social support as well as providing behavioral strategies to manage dementia symptoms for their patients. Some interventions target caregivers alone, but others target caregivers and patients together.

COST-EFFECTIVENESS OF INTERVENTIONS Limited cost-effectiveness data are available to date, with only two trials in patients with dementia, four in caregivers of patients with dementia, and two in patients and caregivers together.

Persons with Dementia For persons with dementia in the United Kingdom, Cognitive Stimulation Ther- apy (CST) based on Reality Orientation and Reminiscence Therapy was more clinically effective than usual care at improving cognitive function and dementia- related quality of life, with cost-effectiveness depending on willingness to pay thresholds. At the end of the eight-week intervention, it cost £75 per incremental improvement on a measure of mental state (Mini-Mental State Exam) and £23 per incremental improvement on a measure of dementia-related quality of life (Qual- ity of Life –Alzheimer’s Disease; Knapp et al., 2006; Spector et al., 2003).

After receiving standard CST biweekly for seven weeks, maintenance (longer- term continuation) of CST for another 24 weeks might be more cost-effective than returning to usual care if limited to healthcare costs but was outside standard willingness to pay thresholds when including societal costs (£64,842 per QALY) after six months. Maintaining CST was also dominated by usual care in terms of incremental improvements on a measure of cognitive function (Alzheimer's Dis- ease Assessment Scale – Cognition Subscale) but may be cost-effective in terms of quality of life at £643 per incremental improvement on a measure of dementia- related quality of life (Quality of Life – Alzheimer’s Disease), depending on the willingness to pay threshold (D’Amico et al., 2015). Note that this is much higher

390 Dementia than the £23 per incremental improvement on this measure from the eight-week intervention.

Table 1. Behavioral Interventions for Persons with Dementia Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness D’Amico et 236 people Intervention: Difference in PP: Societal al. (2015) with mild Maintenance Quality of Life to moderate (longer-term – Alzheimer's Total Costs: Maintenance dementia in continuation) Disease (QoL- I: £16,810.1 Cognitive UK who re- of Cognitive AD): (6,757.7) Stimulation ceived Stimulation 1.78 (95% CI, – C: £15,192.4 Therapy for standard Therapy 0.40 to 3.95) (6,294.1) people with Cognitive weekly for dementia Stimulation another 24 Difference in ICER (per QALY): Therapy weeks. Aver- Alzheimer's £64,842 biweekly age cost Disease As- for 7 weeks. £623/person. sessment Scale ICER (per 1-point 114 in in- – Cognition improvement in tervention, Control: (ADAS-Cog): QoL-AD): 104 in con- Usual care. −0.64 (95% CI, £643 trol. –4.06 to 2.79). Measures: ICER (per 1-point 6 months Lower scores improvement in indicate better ADAS-Cog): cognition. Dominated Knapp et al. 161 people Intervention: Change in PP: Healthcare & (2006) & with de- Cognitive Mini-Mental Social Services Spector et al. mentia liv- Stimulation State Exami- (2003) ing in care Therapy nation ICER (per 1-point homes or based on Re- (MMSE): improvement in Cognitive the com- ality Orienta- I: .9 (3.5) MMSE):

Simulation munity in tion and C: -.4 (3.5) £200175.32 Therapy for UK. 91 in Reminiscence (p<.05) people with interven- Therapy for ICER (per 1-point dementia tion, 70 in 45-minute d: .371 improvement in control. group ses- QoL-AD):

sions twice Change in £200122.82 weekly for 8 Quality of Life weeks. – Alzheimer’s Disease (QoL- Control: AD): Usual care. I: 1.3 (5.1) C: -.8 (5.6) Measures: (p<.05) 8-week follow-up d: .393

391 Dementia

Caregivers of Persons with Dementia A prior systematic review of interventions for informal caregivers of persons with dementia in identified four psychosocial interventions with mixed efficacy. Moreover, it concluded there was insufficient data to draw cost-effectiveness conclusions across any intervention types (Jones et al., 2012). In this review, one study assessed time saved while the remainder assessed the costs of improving caregiver wellbeing.

A home-based behavioral intervention to decrease caregiver stress and improve management of dementia-related behavioral problems decreased the number of hours spent caregiving relative to usual care after six months, and only cost $5 per hour saved per day. Notably, there is probably additional value for this time saved since the freed hours can be allocated to non-caregiving activities, including income-generating activities. However, the researchers did not provide data on any clinical outcomes such as the caregiver’s mental health or quality of life, which are important non-economic factors to consider (Nichols et al., 2008).

To improve coping skills, a manual-based coping intervention delivered at the caregiver’s preferred location (including his/her home) was more cost-effective than no intervention (i.e. usual care for the patient with dementia) for caregivers in the United Kingdom. A recent follow-up analysis confirmed that the original pattern of cost-effectiveness findings after eight months persisted after two years although the probability of the coping intervention being cost-effective was lower. After two years, it cost £11,200 per QALY, with 65% to 75% probability of being more cost-effective than usual care within standard willingness to pay thresholds, and £199 per incremental improvement in a measure of mental health (Hospital Anxiety and Depression Scale), with 78% probability of being more cost-effective than usual care if the value were £500 per incremental improvement (Livingston et al., 2014; Knapp et al., 2013).

To increase social support, one intervention from the Netherlands targeted family members and another from the United Kingdom offered peer support, but both were less cost-effective than usual care. First, a structured family intervention focused on psychoeducation, problem-solving, and existing social networks with both individual counseling sessions and family meetings with relatives and friends (excluding the person with dementia) demonstrated no differences on clinical outcomes or total costs for caregivers, patients, or the combined patient- caregiver dyads relative to usual care after a year. This included no difference in incidence of depression and/or anxiety disorders for caregivers. It is worth noting that within the structured family intervention, only 76% completed even one family meeting and only 46% completed the full intervention; this apparent lack of acceptability or feasibility may have limited clinical and cost-effectiveness (Joling et al., 2013; Joling et al., 2012).

Second, a structured befriending intervention including contact with a facilitator and the option to be paired with a trained volunteer was less cost-effective than usual care after 15 months, exceeding £100,000 per QALY. It is worth noting that only about 50% of the caregivers assigned to the intervention chose the option to be befriended, again suggesting an apparent lack of acceptability of feasibility

392 Dementia that may have limited clinical and cost-effectiveness (Wilson et al., 2009; Charlesworth et al., 2008).

Table 2. Behavioral Interventions for Caregivers of Persons with Dementia Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Livingston et 260 family Intervention: Hospital PP: Healthcare & al. (2014) & carers of Manual-based Anxiety and Social Services Knapp et al. people with coping inter- Depression (2013) dementia in vention deliv- Scale – Total ICER (per QALY): UK. 173 in ered by psy- (HADS-T): 8 months

Coping interven- chology gradu- 8 months £2009-106,000 strategy pro- tion, 87 in ates without I: 12.9 (7.9) gram control. At clinical qualifi- C: 14.9 (8.0) 24 months for family 24 months, cations for 8 £2009-1011,200 carers of 132 in in- sessions over 8- d: .252 people with tervention, 14 weeks at ICER (per 1-point dementia 64 in con- carer’s home or 24 months improvement in (STrAtegies trol. location of I: 13.6 (8.3) HADS): for Rela- preference plus C: 15.5 (9.5) 8 months

Tives, usual treat- £2009-10118 START) ment. Average d: .213 cost 24 months

£232/carer. Health Sta- £2009-10199 tus Ques- Control: tionnaire Willingness to Usual treat- (HSQ) – pay threshold: ment. Mental At values of £20K- Health: £30K/ Measures: 8 months QALY, 93%-99% 8 months & 24 I: 58.6 (22.0) probability at 8 months C: 58.2 (19.2) months and 65%- 75% probability at d: .019 24 months coping intervention more 24 months cost-effective than I: 60.2 (19.8) usual treatment. If C: 55.0 (21.2) value is £500/ incremental im- d: .254 provement on HADS-T, 95% probability at 8 months and 78% probability at 24 months intervention more cost- effective.

393 Dementia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Joling et al. 192 caregiv- Intervention: Incidence of PP: Societal (2013 & ers of per- Family inter- Depressive 2012) sons with vention includ- and/or Anx- ICER (per QALY): dementia in ing 6 individu- iety Disorder caregiver only

Family meet- the Nether- al counseling in Caregiv- –€200932,254 ings to pre- lands. 96 in sessions and 4 ers: vent depres- intervention structured fam- I: 39.5% patient only sion and (39 com- ily meetings C: 35.2% €20092,574,938 anxiety in plete data), with rela- (NS) caregivers of 96 in con- tives/friends patient-caregiver patients trol (48 (typically No significant €2009157,534 with dement complete without person differences on ia data). with dementia) severity of ICER (per inci- every 2-3 depressive dence of depres- months to offer and anxiety sive and/or anxi- psychoeduca- symptoms, ety disorder in tion, teach caregiver bur- caregivers):

problem- den, or health- –€200959,011 solving skills, related quality and improve of life. Willingness to support sys- pay threshold: tems. Estimat- For caregivers, if ed total time value is €0- 6.5 hours. €30K/QALY, 73%-85% proba- Control: bility family in- Usual care. tervention more cost-effective than Measures: usual care; max. 12 months 95%. For patients, If value is €0- €30K, approx. 29% probability; max. 54%. For patient-caregiver dyad, if value is €0-€30K, 33%-36% probability; max. 74%. At no value per incidence of depression or anxiety, 73% probability; as value increases, 57% probability.

394 Dementia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Wilson et al. 236 caregiv- Intervention: Hospital PP: Societal (2009) & ers of pa- Structured be- Anxiety and Charles- tients with friending ser- Depression ICER (per QALY): worth et al. dementia in vice including Scale Caregivers only

(2008) the United contact from (HADS): £2005105,954 Kingdom. Befriender Fa- Anxiety sub- Befriending 116 in in- cilitator and scale Patient-caregiver caregivers of tervention, offer to be I: 7.5 (4.5) dyads patients with 120 in con- matched with C: 7.9 (4.6) £200526,848 dementia trol. trained volun- (BEfriending teer Befriender d: .088 Willingness to and Costs of based on com- pay threshold: CAring, panionship ra- Depression If value is £30K/ BECCA) ther than prac- subscale QALY, 42.2% tical help. I: 6.7 (3.6) probability struc- C: 6.9 (3.9) tured befriending Control: service more cost- Usual care. d: .053 effective than usual care for Measures: QALYs: caregivers and 15 months I: .946 51.4% probability C: .929 for caregivers and (NS) patients. Nichols et al. 92 caregiv- Intervention: Hours PP: Time (2008) ers of pa- Home-based Providing tients with behavior- Care: ICER (per addi- Behavioral dementia in al intervention I: 5.8 (4.0) tional hour not intervention U.S. 46 in to decrease C: 8.4 (4.4) spent caregiving for caregiv- interven- caregiver stress (p=.01) per day): ers of pa- tion, 46 in and improve $4.96 tients with control. dementia man- d: .619 dementia agement with (Resources 12 individual for Enhanc- sessions (9 ing Alzheim home, 3 phone) er's Caregive and 5 group rs Health, phone sessions. REACH II) Average cost $1,214/person.

Control: Usual care with two check-in phone calls. Average cost $54/person.

395 Dementia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Measures: 6 months

Persons with Dementia and their Caregivers While the prior section’s interventions targeted caregivers but measured outcomes for both caregivers and patients, a few interventions targeted caregivers and patients together. In this case, one was cost-effective but the other was not.

In the United Kingdom, joint reminiscence groups for patients with dementia and their caregivers were less cost-effective than usual care after ten months, with no clinical differences but higher intervention costs. Overall, it cost £2,586 per incremental improvement in a measure of the patient’s quality of life (Quali- ty of Life – Alzheimer’s Disease), which appears high (Woods et al., 2012). In the Netherlands, occupational therapy incorporating cognitive and behavioral interventions for patients with dementia and their caregivers was cost-saving over usual care at $2,621 saved per successful treatment (improvements in patient daily functioning and caregiver sense of competence), with 94% likelihood of dominating usual care (Graff et al., 2008).

Table 3. Behavioral Interventions for Patients with Dementia and Their Caregivers Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Woods et al. 350 dyads of Intervention: Quality of PP: Healthcare (2012) patients with Joint reminis- Life – Alz- & Social Ser- mild to mod- cence groups heimer's Dis- vices Reminis- erate dementia for patients ease (QoL- cence groups ad their family and caregiv- AD): ICER (per 1- for people caregivers in ers for twelve I: 36.63 (5.63) point improve- with demen- UK. 206 in in- weekly ses- C: 35.96 (5.28) ment in QoL- tia and their tervention, 144 sions then 7 AD): family care- in control. monthly d: .123 £2,586 (95% CI, givers maintenance £20,280 to (REMCARE) sessions. Av- No significant £24,340) erage cost differences on £9,433/dyad. any primary or Given higher secondary out- costs and no clini- Control: comes for pa- cal differences ac- Usual care. tients or care- ceptability curves givers. not calculated. Measures: 10 months Graff et al. 132 persons Intervention: Patient Daily PP: Societal (2008) with mild to Community- Functioning moderate de- based occu- (AMPS- ICER (per suc- Occupational mentia and pational ther- Process cessful treat- therapy for their caregiv- apy for pa- Scale): ment):

396 Dementia

Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness patients with ers in the tients and I: .2 (.8) –$2,621 dementia Netherlands. caregivers C: .3 (.8) and their 67 in interven- including Willingness to caregivers tion, 65 in con- cognitive and d: .125 pay threshold: trol. behavioral 94% probability interventions Patient Dete- occupational to train pa- rioration in therapy domi- tients on aids Daily Activi- nated usual to compen- ties (IDDD- care. If value is sate for cog- Performance $2,933 (€2,000) nitive decline Scale): per successful and caregiv- I: 23.5 (7.9) treatment, 99% ers on coping C: 24.5 (8.7) probability behaviors for more cost- ten 1-hour d: .120 effective. sessions over 5 weeks. Cost Caregiver $1,738/dyad. Sense of Competence: I: 89.7 (14.9) Control: C: 90.4 (13.6) Usual care. d: .049 Measures: 3-month fol- Percent Clini- low-up cally Success- ful Treat- ment: I: 37% C: 1.5%

Significant differences in all three primary outcomes, which were combined into one successful treatment outcome.

LIMITATIONS AND FUTURE DIRECTIONS Most cases of dementia are progressive and irreversible. Dementia prevalence will continue to increase with the aging of the population and advances that pro- long life, adding to the already tremendous economic burden on healthcare and social services as well as on informal caregivers. It is well established that the re-

397 Dementia liance on informal caregiving in the home by family members and friends exerts a significant physical, emotional, and financial toll on the caregiver. In short, interventions to both alleviate symptoms for dementia and caregiving and to reduce associated costs for both patients and caregivers are of utmost importance.

Given the limited efficacy of pharmacotherapy in delaying progression or managing symptoms, psychosocial interventions could make a meaningful contribution. Only two studies on psychosocial interventions for persons with dementia included cost-effectiveness data. This may be in part due to the limited data supporting clinical efficacy of potential interventions. Some studies suggest that behavioral and cognitive interventions can be frustrating for persons with dementia, with only modest benefits. Interventions focused on emotional outcomes and quality of life could be key avenues of further research.

For caregivers who may already be overwhelmed and overburdened, conven- ience seems to be a critical component of their ability to participate in and benefit from potential interventions. Two interventions designed to promote social support had low completion rates and did not demonstrate cost-effectiveness over usual care. Meanwhile, two home-based interventions (one at caregiver’s preferred location, which was typically the home) were cost-effective in terms of both time and money. Further, combining interventions for persons with dementia and their caregivers may help maximize cost-effectiveness.

One economic argument in favor of caregiver interventions is that if the caregiver feels better and enabled to continue to provide care, it may delay the need for the person with dementia to enter an inpatient care facility (e.g., nursing home); delaying entry to inpatient care would decrease the associated costs of those services. However, whether these savings compensate for the indirect costs of the caregiver, both in terms of their out-of-pocket expenditures as well as the trade- off of their own earning potential, warrants further investigation.

Overall, more research is needed to develop a strong evidence base for clinically effective interventions for both patients with dementia and their caregivers. After that, studies demonstrating cost-effectiveness should follow.

KEY POINTS

Persons with Dementia • Cognitive Stimulation Therapy, combining Reality Orientation and Reminis- cence Therapy, may be more cost-effective than usual care at £75 per incremental improvement in cognitive function and £23 per incremental improvement in dementia-related quality of life, depending on willingness to pay thresholds. • After standard Cognitive Stimulation Therapy, maintenance (longer-term continuation) of Cognitive Stimulation Therapy was less cost-effective than returning to usual care at £64,842 per QALY after six months. It was also dominated by usual care per incremental improvement in cognitive function,

398 Dementia

but could be cost-effective at £643 per incremental improvement in dementia- related quality of life, depending on the willingness to pay threshold.

Caregivers of Persons with Dementia • A home-based behavioral intervention to decrease caregiver stress and improve patient management significantly decreased the number of hours spent caregiving relative to usual care after six months, only costing $5 per non- caregiving hour per day, but did not look at health or quality of life outcomes. • A coping strategy intervention at the caregiver's preferred location was more cost-effective than no intervention after two years, at £11,200 per QALY, and might also be more cost-effective at £199 per incremental improvement in caregiver’s mental health, depending on the willingness to pay threshold. • A structured family intervention with individual counseling and family meetings (excluding person with dementia) focused on psychoeducation, problem-solving, and social support was less cost-effective than usual care for the caregiver, patient, or caregiver-patient dyad in either quality of life or incidence of depressive and anxiety disorders in the caregiver after a year. • A structured befriending intervention with the option for the caregiver to be paired with a trained volunteer to befriend was less cost-effective than usual care at £105,954 per QALY after 15 months.

Persons with Dementia and their Caregivers • Joint reminiscence groups for patients with dementia and their caregivers were less cost-effective than usual care after ten months, with no clinical differences and higher intervention costs leading to an incremental cost of £2,586 per incremental improvement on the patient’s quality of life. • Occupational therapy including cognitive and behavioral interventions for persons with dementia and their caregivers was cost-saving over usual care at $2,621 saved per successful treatment (i.e. improvements in patient daily functioning and caregiver sense of competence).

REFERENCES Brookmeyer R, Evans DA, Hebert L, Langa KM, Heeringa SG, Plassman BL, Ku- kull WA. National estimates of the prevalence of Alzheimer's disease in the Unit- ed States. Alzheimers Dement. 2011 Jan;7(1):61-73.

Charlesworth G, Shepstone L, Wilson E, Thalanany M, Mugford M, Poland F. Does befriending by trained lay workers improve psychological well-being and quality of life for carers of people with dementia, and at what cost? A randomised controlled trial. Health Technol Assess. 2008 Mar;12(4):iii, v-ix, 1-78.

D'Amico F, Rehill A, Knapp M, Aguirre E, Donovan H, Hoare Z, Hoe J, Russell I, Spector A, Streater A, Whitaker C, Woods RT, Orrell M. Maintenance cognitive stimulation therapy: an economic evaluation within a randomized controlled trial. J Am Med Dir Assoc. 2015 Jan;16(1):63-70.

Graff MJ, Adang EM, Vernooij-Dassen MJ, Dekker J, Jönsson L, Thijssen M, Hoefnagels WH, Rikkert MG. Community occupational therapy for older pa-

399 Dementia tients with dementia and their care givers: cost effectiveness study. BMJ. 2008 Jan 19;336(7636):134-8.

Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013 May 7;80(19):1778-83.

Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary costs of dementia in the United States. N Engl J Med. 2013 Apr 4;368(14):1326-34.

Joling KJ, Bosmans JE, van Marwijk HW, van der Horst HE, Scheltens P, Vroomen JL, van Hout HP. The cost-effectiveness of a family meetings intervention to prevent depression and anxiety in family caregivers of patients with dementia: a randomized trial. Trials. 2013 Sep 22;14:305.

Joling KJ, van Marwijk HW, Smit F, van der Horst HE, Scheltens P, van de Ven PM, Mittelman MS, van Hout HP. Does a family meetings intervention prevent depression and anxiety in family caregivers of dementia patients? A randomized trial. PLoS One. 2012;7(1):e30936.

Jones C, Edwards RT, Hounsome B. A systematic review of the cost-effectiveness of interventions for supporting informal caregivers of people with dementia re- siding in the community. Int Psychogeriatr. 2012 Jan;24(1):6-18.

Knapp M, King D, Romeo R, Schehl B, Barber J, Griffin M, Rapaport P, Living- ston D, Mummery C, Walker Z, Hoe J, Sampson EL, Cooper C, Livingston G. Cost effectiveness of a manual based coping strategy programme in promoting the mental health of family carers of people with dementia (the START (STrAte- gies for RelaTives) study): a pragmatic randomised controlled trial. BMJ. 2013 Oct 25;347:f6342.

Knapp M, Thorgrimsen L, Patel A, Spector A, Hallam A, Woods B, Orrell M. Cognitive stimulation therapy for people with dementia: cost-effectiveness analysis. Br J Psychiatry. 2006 Jun;188:574-80.

Livingston G, Barber J, Rapaport P, Knapp M, Griffin M, Romeo R, King D, Liv- ingston D, Lewis-Holmes E, Mummery C, Walker Z, Hoe J, Cooper C. START (STrAtegies for RelaTives) study: a pragmatic randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of a manual-based coping strategy programme in promoting the mental health of carers of people with dementia. Health Technol Assess. 2014 Oct;18(61):1-242.

Nichols LO, Chang C, Lummus A, Burns R, Martindale-Adams J, Graney MJ, Coon DW, Czaja S; Resources for Enhancing Alzheimer's Caregivers Health II Investigators. The cost-effectiveness of a behavior intervention with caregivers of patients with Alzheimer's disease. J Am Geriatr Soc. 2008 Mar;56(3):413-20.

Qaseem A, Snow V, Cross JT Jr, Forciea MA, Hopkins R Jr, Shekelle P, Adelman A, Mehr D, Schellhase K, Campos-Outcalt D, Santaguida P, Owens DK; Ameri-

400 Dementia can College of Physicians/American Academy of Family Physicians Panel on Dementia. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008 Mar 4;148(5):370-8.

Spector A, Thorgrimsen L, Woods B, Royan L, Davies S, Butterworth M, Orrell M. Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial. Br J Psychiatry. 2003 Sep;183:248- 54.

Wilson E, Thalanany M, Shepstone L, Charlesworth G, Poland F, Harvey I, Price D, Reynolds S, Mugford M. Befriending carers of people with dementia: a cost utility analysis. Int J Geriatr Psychiatry. 2009 Jun;24(6):610-23.

Woods RT, Bruce E, Edwards RT, Elvish R, Hoare Z, Hounsome B, Keady J, Moniz-Cook ED, Orgeta V, Orrell M, Rees J, Russell IT. REMCARE: reminiscence groups for people with dementia and their family caregivers - effectiveness and cost-effectiveness pragmatic multicentre randomised trial. Health Technol Assess. 2012;16(48):v-xv, 1-116.

401 End of Life Care

CHAPTER 18: END-OF-LIFE CARE

ABSTRACT Priorities shift as people approach death. This is particularly evident in terms of medical treatment, which typically prioritizes life-saving or life-extending efforts. End-of-life care is gaining prominence as an effective means to increase quality of care, enhance comfort, manage symptoms, and improve quality of life during a patient’s last months.

End-of-life care, in turn, has the potential to lead to substantial cost-savings by honoring a patient’s wishes while decreasing excessive healthcare utilization. A quarter of Medicare spending for healthcare for the elderly is provided for care during the last year of beneficiaries’ lives, and of that last year spending, 40% occurred during the last 30 days of life. In addition, end-of-life care can take a significant and often unmeasured toll on informal caregivers such as family and friends who provide 90% of all in-home end-of-life care. In the United States, end-of-life care accounts for 10% to 12% of national healthcare spending, and informal care costs the equivalent of 18% of national healthcare spending.

Systematic reviews for end-of-life interventions repeatedly note the lack of cost- effectiveness data. While hospice care is technically limited to terminal illnesses and a prognosis of less than six months to live, palliative care is applicable for illnesses throughout the lifespan; however, here we focus on end-of-life palliative care. Based on Medicare data, hospice care has demonstrated mixed cost- effectiveness findings. A recent analysis concluded that the costs of providing hospice services exceeded the savings hospitals achieved by preventing unnecessary or undesired health care interventions; however, another analysis limited to poor-prognosis cancer patients found hospice care cost-saving. Meanwhile, most palliative care interventions cost the same or less than usual care. While palliative care does not typically improve health or delay mortality, it does improve outcomes of greater priority near end-of-life (e.g., completing advanced directives, honoring patient’s choice for where they die). Three separate interventions of nurse-led follow-up including additional support, information, coordination of services, and, in some cases, empowerment found one was less expensive than and two similarly expensive to usual care, with the latter two significantly improving patient satisfaction, quality of life, and mood. These findings suggest nurse-based programs may be cost-effective.

Interventions of interdisciplinary specialist teams at the hospital, clinic, or home were mostly less expensive than usual care, in large part by decreasing use of hospital services. Only one palliative care intervention had higher costs than usual care; this may be explained in part by the fact that it included home-based primary care and was from the Veterans Health Administration, where usual care already offers a higher level of interdisciplinary support. In general, the majority of studies support the hypothesis that end-of-life palliative care interventions reduce healthcare utilization and decrease associated costs without reducing quality of life. In cases where these trends are lacking, reasonable explana- tions (e.g., types of patients, intensity of services) may help account for the dif-

402 End of Life Care ferences. Nonetheless, more data are needed to definitively confirm the economic value of end-of-life care.

BACKGROUND ON END-OF-LIFE CARE Palliative care encompasses supportive care for those with terminal and nonterminal serious illnesses, and thus can occur throughout the lifespan. Hospice care, at least in the United States, is limited to those with a terminal illness and estimated to have at most six months to live. Thus, hospice care can be considered a specific type of palliative care. However, the terms palliative care and hospice care are not used consistently and sometimes used interchangeably. Importantly, while palliative care is not limited to terminal cases or to those who have forgone curative care, together these services are often referred to as end-of-life care.

Unlike most of the healthcare system, these end-of-life services focus minimally on treatment or extending years of life, instead emphasizing comfort and quality of life for whatever time remains. These services strive to alleviate suffering and enable meaningful activities within the constraints of any illnesses (e.g., pain management). For some, palliative care is a philosophical approach that expands beyond treating the physical and medical to incorporate broader aspects such as the psychological, social, and spiritual. These differences in priorities for end-of- life care mean that the relevant outcomes to assess efficacy must also be different.

Informal Caregivers Informal caregivers (typically family members or friends) are an understudied but critical component of the end-of-life ecosystem. Importantly, informal caregiving often has a significant impact on caregivers themselves, worsening their physical and mental health and depleting their financial resources. Spousal caregivers face unique challenges compared to parental or child caregivers as they more often live with the care recipient, have less choice regarding contributions to care-giving, and often have their own health concerns due to their similar age (Adelman et al., 2014).

PREVALENCE The elderly population (i.e. 65 years and older) is growing rapidly in the United States, from 4% of the total population in 1900 to 8.1% in 1950 to 13% in 2010. The increase of 5 million additional older adults between 2000 and 2010 represented a 15% increase. Even more striking, the total percentage is estimated to increase to 20% (70 million people) by 2030. The proportion of the elderly population that is 85 years and older is similarly increasing, from 4% in 1900 to 12.6% in 2010 (an increase of 30% in 10 years). By 2030, this proportion is estimated to double (Rice & Fineman, 2004; Hughes & Smith, 2014).

Unsurprisingly, health tends to deteriorate with age. These health deficits are compounded by the increasing prevalence of chronic conditions. In 2012, about 50% of adults (117 million people) had at least one chronic disease; in 2005, 25% of them had limitations in their activities of daily living. Among older adults, over 65% had multiple chronic conditions, which utilizes a disproportionate amount of healthcare resources (see Supplement on Multimorbidity for further details). Overall, 70% of deaths were attributable to chronic disease in 2005.

403 End of Life Care

However, the proportion of elderly people experiencing disability appears to be on the decline. This, in turn, has led to a decrease in mortality rates for diseases that occur more commonly in old age, like heart disease and stroke, and an increase in life expectancy (Rice & Fineman, 2004; Hughes & Smith, 2014).

The majority of studies on palliative care focus on cancer, while the most common illnesses that would benefit from palliative care include cancer (34%), cardiovascular disease (38.5%), chronic obstructive pulmonary disease (10.3%), and HIV and AIDS (5.7%). Dementia, an illness of increasing prevalence and concern, often has poor end-of-life outcomes and may also benefit from palliative care (Dzingina & Higginson, 2015; see Chapter 17 on Dementia). It has been well established that more than half of people would prefer to be cared for and die at home if they are able (Gomes et al., 2013), but that nearly 60% of these deaths occur in hospitals (Weitzen et al., 2003). Notably, those who use hospice services are much more likely to die at home than those who do not (68% versus 16%; Raphael et al., 2001).

The demand for palliative care is increasing. In the last ten years, two-thirds of hospitals offered palliative care and more than 1,000 new hospital-based palliative care programs were established. Hospice care is provided to approximately 1.65 million patients per year, with about 45% of all deaths occurring within a hospice program in 2011 (Hughes & Smith, 2014). Finally, older adults who are already in long-term care programs may have hospice care options readily available. By one estimate, 4.3% of adults over the age of 65 and 18.2% of adults over the age of 85 were under nursing home care as of 1999, although data suggest these rates may be declining for various reasons including both the decline in disability and the availability of alternative options (Rich & Fineman, 2004).

Informal Caregivers Ninety percent of in-home care is provided by informal caregivers (e.g., family members and friends), involving around 65.7 million caregivers for adults or children with chronic illnesses as of 2009. As mentioned earlier, caregiving can be physically and emotionally taxing for the caregiver, with almost a third of caregivers reporting high caregiver burden (Adelman et al., 2014).

ECONOMIC BURDEN OF END-OF-LIFE CARE End-of-life care accounts for 10% to 12% of national healthcare spending. Long- term care (which includes home care and nursing home care) cost $132.1 billion in 2001, or about 9.6% of personal healthcare spending (Rich & Fineman, 2004). A recent analysis of Medicare data indicated that hospice use doubled from 23% in 2000 to 47% in 2012, and that hospice costs quintupled ($2.9 billion to $15.1 billion) in the same time period (Gozalo et al., 2015). Given the common preference to die at home, it is worth noting that costs are double for those who die in the hospital rather than elsewhere, including at home (Raphael et al., 2001).

On average, healthcare costs increase with age, explaining why the elderly population accounts for an asymmetric proportion of total healthcare costs. As one example, in 1999, the elderly comprised 13% of the population but accounted for 31% of national healthcare expenditures. Moreover, these costs are expected to

404 End of Life Care increase, with projections estimating an increase from 4.3% of the GDP in 1995 to 10% of the GDP in 2020 (Rich & Fineman, 2004). Significantly, many ailments en- demic to older age (ranging form hip replacement to heart disease to dementia) have high economic burdens of their own.

End-of-life care accounts for a substantial proportion of health care costs for the elderly, with about 25% of Medicare expenditures occurring in the last year of life and 40% of those expenditures occurring in the last 30 days of life. This first percentage has not changed significantly in the preceding 30 years (from 27% to 31% in earlier decades) even though services have changed significantly (Riley & Lubitz, 2010; Rice & Fineman, 2004; Raphael et al., 2001). Interestingly, between the ages of 65 to 85 years, healthcare costs per capita for the last year of life decrease with increasing age while nursing home costs per capita increase with increasing age (Rice & Fineman, 2014).

Informal Caregivers In addition to the economic burden on the healthcare system, end-of-life care also has a significant burden on patients and their families that often goes unmeasured and unreimbursed (e.g., out-of-pocket spending, patient’s lost income, caregiver’s opportunity cost in forgoing full-time employment). For instance, one large-scale study found that more than half of families of persons with serious illnesses experienced at least one major burden, including 17% making a major change to family plans and 20% of caregivers making a major life change (e.g., taking time off work or quitting their job; Boni-Saenz et al, 2011). Informal caregiving (not limited to end-of-life care) was estimated to cost $196 billion annually, or the equivalent of 18% of national healthcare spending, based primarily on lost wages and social security payments (Raphael et al., 2001).

What Matters Most Discussing anything related to costs for end-of-life care can be particularly complex due to the emotional tenor of decisions related to death and dying. This in- vokes broader moral concerns beyond maximizing limited resources. Some argue that the personal or social benefits of extending life, especially for themselves or beloved family members, are incalculable and thus exceed any associated costs. Others argue that the ethos of palliative care is diametrically opposed to concerns about economic efficiency. Nonetheless, the growing elderly population—due to aging baby boomers, improved health outcomes, and increased longevity—risks taxing the entire healthcare system beyond its capabilities.

CLINICALLY EFFECTIVE INTERVENTIONS Over the past 20 years, palliative care has most commonly been offered as interdisciplinary, hospital-based consultation teams, usually experts trained in palliative care and comprised of specialties such as physicians, nurses, social workers, and chaplains. Additional specialists can also be recruited as needed to target specific patient concerns. It is recommended these services be available to the patient and their families 24 hours a day, seven days as week, although it is worth investigating less resource-intensive options to promote cost-effectiveness.

405 End of Life Care

In addition to managing physical and psychological symptoms, palliative care teams can assist patients and families in broader concerns: educate and support them in their healthcare choices; help articulate their end-of-life wishes and for- mulate a personalized care plan; address their social, cultural, and spiritual concerns; and communicate their evolving plan and related concerns to relevant par- ties. Some data also support integrating palliative care services into primary care or other outpatient settings (e.g., oncology clinics); however, hospital-based consulting specialist teams and integrated primary care services for palliative care have not been compared to each other (Hughes & Smith, 2014). Alternative delivery formats, such as nurse-led follow-up services, are also being investigated.

In general, palliative care has been found to provide significant benefits for patients, including better quality of care, improved quality of life, improved symptom management, increased success in honoring patient choice in place of death, increased satisfaction for patients and providers, decreased emotional distress for patients and caregivers, and, in some cases, increased survival and reduced caregiver burden (Hughes & Smith, 2014; Dzingina & Higginson, 2015). Notably, palliative care is not concerned with and has not demonstrated consistent benefits for traditional measures of clinical efficacy such as improving health or prolonging mortality.

COST-EFFECTIVENESS OF INTERVENTIONS Limited analyses are available on the cost-effectiveness of end-of-life care, including for different illnesses (e.g., cancer versus dementia). Moreover, most data focus on the healthcare system with limited data of the economic impact for patients and their families; for example, an increase in out-of-pocket costs.

Hospice Care Not all end-of-life care has demonstrated cost-savings, with mixed data of decreased, unchanged, and increased costs for hospice care. In general, cost-savings increase with longer in hospital lengths of stay, but there is immense variation in average length of stay (Taylor et al., 2007). Notably, hospice use expanded from 2004 to 2009, with average lengths of stay increasing from 72.1 to 92.6 days. This increase in hospice use also shifted the types of patients receiving care (e.g., more non-cancer patients).

A recent analysis of Medicare data, comparing a subset of patients from 2009 who used hospice with matched patients from 2004 who did not use hospice but would have likely used it if they had died in 2009, found the costs of hospice care exceeded the savings from other types of care. In other words, while hospice care did significantly decrease “aggressive” end-of-life outcomes (hospital transfers, feeding tube use, ICU use), these savings were less than the additional costs of providing hospice care (Gozalo et al., 2015). On the other hand, an analysis limited to patients with poor-prognosis cancer found hospice care not only significantly decreased “aggressive” outcomes (hospitalizations, ICU admissions, inva- sive procedures) but also lowered costs during the last year of life. Estimated savings were up to $1.79 billion annually (Obermeyer et al., 2014; Powers et al., 2015). Perhaps hospice care only has cost-savings for cancer patients, while expanded hospice services including more non-cancer patients do not reveal these

406 End of Life Care economic benefits. Clearly, more data are needed to confirm or refute the saving trends that have been identified thus far.

Palliative Care A systematic review only identified one cost-effectiveness analysis. Nonetheless, palliative care leads to fewer and shorter emergency room visits and hospitalizations including during the last month of life, which could save money by shifting care from higher cost settings to lower cost ones (i.e. cost avoidance). Most studies found lower direct costs in palliative care interventions, although the differences were only significant in for a subset of them (Smith et al., 2014).

A meta-review limited to hospital-based palliative care did not identify any for mal cost-effectiveness analyses, but all palliative care interventions had lower hospital-related costs (9% to 25%) compared to usual care (May et al., 2014). A review limited to home-based palliative care noted cost-effectiveness data was inconclusive, with clinical benefits for specific patient outcomes (especially for cancer) but not for caregiver outcomes (Gomes et al., 2013; Gomes et al., 2014). Lastly, a review limited to telehealth palliative care to provide information and improve communication did not identify any randomized controlled trials; however, available data suggested telehealth palliative care was effective at improving communication and quality of care and reducing costs (Capurro et al., 2014). In all cases, cost-effectiveness analyses to combine costs and improvements for different interventions are still needed and should include direct and indirect costs within and outside the healthcare system.

Randomized Controlled Trials In the absence of definitive data, we present studies that included randomized controlled trials and at least some measures of outcomes and related costs.

Nurse-Led Follow-Up Interventions Three separate studies on cancer patients assessed palliative care services or follow-up provided by nurses.

For patients with terminal cancer in the United Kingdom, a nurse-based coordination service supported patients in accessing resources based on individual needs. The nurses did not provide any nursing care, specialist palliative care, or counseling services. While there were no significant differences in outcomes for either patients or their families, the coordination service was less expensive than standard services (41% fewer costs per patient). These differences persisted when analyses were limited to participants who died during the study (i.e. more severe cases; Raftery et al. 1996). A similar intervention for patients with lung cancer in the United Kingdom assigned a clinical nurse specialist for monthly follow-up to provide information and support and to coordinate services either in person or via phone. In this case, nurse-led follow-up cost the same as conventional medical follow-up, but it increased patient satisfaction and was considered timely, which might support cost-effectiveness (Moore et al., 2002).

A phone-based psychoeducational intervention for patients with new diagnoses of advanced cancer delivered by an advanced practice nurse expanded services

407 End of Life Care beyond the information, support, and coordination of the two prior interventions to encourage patient activation, self-management, and empowerment through problem-solving, symptom management, advance care planning, treatment decision-making, and communication. There were significant improvements in quality of life and mood and non-significant improvements in symptom intensity compared to standard oncology care, without any differences in hospital resource utilization (proxy for healthcare costs) over three years (or until death), which suggested cost-effectiveness (Bakitas et al., 2009).

Table 1. Nurse-Led Follow-Up Palliative Care Interventions Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Bakitas et al. 322 patients Intervention: Difference in PP: Healthcare (2009) with newly Nurse-led Functional diagnosed ad- phone-based Assessment Resource Use: Palliative vanced cancer psychoeduca- of Chronic Days in hospital care for ad- (e.g., progno- tional inter- Illness Ther- I: 6.6 vanced can- sis of approx. vention to apy-Palliative C: 6.5 cer 1 year). 145 in encourage (higher scores (NS) (Project Edu- intervention, patient acti- indicate better cate, Nur- 134 in control. vation, self- quality of life): Days in intensive ture, Advise, management, 4.6 (SE 2) care unit Before Life & empower- (p=.02) I: .06 Ends, ment via C: .06 ENABLE II) problem- Difference in (NS) solving, Edmonton symptom Symptom As- Emergency de- management, sessment partment visits advance care Scale: I: .86 planning, -27.8 (SE 15) C: .63 treatment de- (p=.06) (NS) cision- making, and Difference in Resource use as a communica- Center for proxy for associ- tion with 4 Epidemiolog- ated costs. weekly ses- ical Studies- sions then Depression: monthly ses- -1.8 (SE, .81) sions until (p=.02) death.

Control: Usual oncology care.

Measures: 3 years (or until death)

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Moore et al. 202 patients Intervention: Median Per- PP: Healthcare (2002) with lung can- Nurse-led fol- cent Patient’s and Social Care cer expected low-up to Overall Rat- Nurse-led to survive at provide in- ing of Care: Median Costs follow-up for least 3 months formation 3 months (per patient*): lung cancer in UK. 99 in and support I: 93.0% 3 months intervention, and coordi- C: 78.0% I: $221.50 103 in control. nate services (p=.002) C: $288.50 monthly by 6 months 6 months phone or in I: 89.0% I: $369.50 clinic. Cost C: 83.0% C: $364.00 estimated at (p=.04) £150/patient 12 months /month. 12 months I: $696.50 I: 93.0% C: $744.50 Control: C: 81.5% Conventional (p=.08) *Intervention cost medical fol- not included. low-up with Percent Died routine out- During patient ap- Study: No significant pointments. I: 73% differences at any C: 67% time point. Measures: 3, 6 & 12 Median months (or Number of until death) Months to Symptomatic Progression: I: 6.0 C: 10.2 (p=.01)

Median Number of Months to Objective Progression: I: 8.3 C: 10.2 Raftery et al. 167 terminally Intervention: Mean Hospi- PP: Societal (1996) ill cancer pa- Nurse-led tal Admis- tients with coordination sions: Mean Cost (per Coordinat- prognosis of service to en- I: 2.5 (3.3) patient): ing service less than a sure patient C: 3.3 (3.0) I: £4,774 for terminal year in UK. 86 access to ap- (NS) C: £8,034

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness cancer in interven- propriate re- d: .254 (p=.006) tion, 81 in con- sources tai- trol. lored to their Mean Inpa- changing tient Days: Direct and indi- needs and I: 24. 1 (30.6) rect costs by pa- circumstanc- C: 40.0 (48.7) tients and families es. Total cost (p=.02) were small and £70,000 (sala- d: .401 showed no signifi- ry plus over- cant differences, head). Mean Outpa- so not included in Control: tient Attend- analysis. Standard ser- ances: vices. I: 18.0 (9.0) C: 10.1 (10.3) Measures: (NS) Until death. d: .817

Mean Nurse Home Visits: I: 14.5 (22.0) C: 37.5 (67.4) (p=.01) d: .516

Percentage Who Died Before Study End: I: 67% C: 79% (NS)

Interdisciplinary Specialist Team Interventions Interdisciplinary specialist teams provide the majority of formal palliative care. For patients with advanced serious illness or their surrogate decision-makers, a coordinated care program to improve care and prepare for end-of-life (e.g., health literacy) delivered by allied health professionals (e.g., nurses, social workers) appeared to be more cost-effective than usual care. After six months, the coordinated care program improved patient satisfaction, increased completion of advanced directives, and decreased problems without any significant differences in healthcare costs per patient; further, there was a trend toward lower costs (25% less) in the coordinated care program (Engelhardt et al., 2006).

A hospital-based interdisciplinary palliative care team (doctor, nurse, social worker, chaplain) for symptom management, psychosocial and spiritual support,

410 End of Life Care end-of-life planning, and post-hospital care appeared to be more cost-effective than usual hospital care for patients with life-limiting illnesses. While there were no differences in quality of life, symptoms, or mortality, the palliative care intervention increased patient satisfaction, days of hospice use, and completion of advance directives with significantly lower healthcare costs at six months post- discharge ($14,486 versus $21,252). These cost savings were mainly driven by a decrease in ICU admissions, not general hospital readmissions (Gade et al., 2008).

Another interdisciplinary palliative care team (palliative care consultant, clinical nurse specialist, administrator, psychosocial provider) in the United Kingdom met the patient at their preferred location (hospital, outpatient clinic, nursing home, personal home) for up to three contacts in-person and/or by phone and was cost-saving for patients with advanced multiple sclerosis and their caregivers. After only three months, this short-term intervention saved £1,789 over usual care. These cost savings were driven mainly by lower use of primary and acute hospital services, but cost-effectiveness is also supported via improved pain outcomes for patients, and reduced burden for caregivers (Higginson et al., 2009).

Two studies assessed home-based care. Another interdisciplinary palliative care team (physician, nurse, social worker, additional members as needed) provided pain and symptom relief as well as education and training to enhance comfort, manage symptoms, and improve quality of life for home-bound terminally ill patients and their families. Compared to usual care, the in-home palliative care intervention led to significantly higher patient satisfaction and a higher percentage of patients dying at home after three months, while being significantly less expensive overall (33%) and per day per patient. Lower costs were due in part to fewer emergency room visits or hospital admissions (Brumley et al., 2007).

For the Veterans Health Administration (VHA), an interdisciplinary team-based primary care program delivered at home for patients with two or more impairments in activities of daily living, a terminal illness, congestive heart failure, or chronic obstructive pulmonary disease was more effective and more expensive than standard VHA and private sector care. Unlike other palliative care interventions, this also includes primary care delivery, with the in-home team including a home-based primary care physician and 24-hour availability. After 12 months, the total costs were significantly higher than usual care (12.1%), driven by significantly higher VHA costs (non-VHA costs were significantly less). While there were no improvements in functional status, other improvements might justify the higher costs: Terminal patients, had significant improvements in most quality of life outcomes (6 of 8), and nonterminal patients had significant improvements in most patient satisfaction outcomes (5 of 6; Hughes et al., 2000).

Table 2. Interdisciplinary Specialist Team Palliative Care Interventions Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Higginson et 46 patients Intervention: Mean Differ- PP: Societal al. (2009) with advanced Multi- ence from multiple scle- professional Baseline on Mean Difference

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Palliative rosis and palliative care Palliative in Total Costs: care team for caregivers in team includ- Care Out- −£1,789 (95% CI, multiple UK. 25 in in- ing part-time come Scale-8 −5,224 to 1,902) sclerosis tervention, 21 palliative (POS-8): in control. medicine Total score POS-8 consultant, I: −0.42 (95% 33.8% probabil- part-time CI, −2.50 to ity palliative clinical nurse 1.67) care team domi- specialist, C: −0.95 (95% nates usual care, administra- CI, −2.87 to 54.9% probabil- tor, and psy- 0.97) ity it has lower chosocial Pain subscale costs but also provider at I: −0.46 (95% worse out- hospital or CI, −0.98 to comes. patient loca- 0.05; p=.028) tion (e.g., C: 0.30 (95% ZBI-12 home, outpa- CI, −0.16 to 47.3% probabil- tient clinic, 0.76) ity palliative nursing d: .6 care team domi- home) for 1- 3 nates usual care, contacts (vis- Mean Differ- 48.0% probabil- its and/or ence from ity it has higher phone calls). Baseline on costs but also Zarit Carer better outcomes. Control: Burden In- Usual care for ventory (ZBI- 3 months. 12): I: −2.88 (95% Measures: CI, −5.99 to 12-week fol- 0.24; p=.011) low-up C: 1.58 (95% CI, −0.51 to 3.67) d: 1.3 Gade et al. 512 patients Intervention: Patient Satis- PP: Healthcare (2008) hospitalized Interdiscipli- faction: with life- nary pallia- Place of Care Total Healthcare Hospital- limiting ill- tive care team Environment Costs (per pa- based inpa- nesses (e.g., with pallia- Scale (i.e. Hos- tient): tient pallia- prognosis to tive care phy- pital) I: $14,486 tive care die within 1 sician, nurse, I: 6.8 (1.0) (17,361) team for life- year). 275 in social worker, C: 6.4 (1.1) C: $21,252 limiting ill- intervention, and chaplain (p<.001) (25,197) nesses 237 in control. focused on d: .381 (p=.001) symptom d: .318 management, Doctors, Nurs-

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness psychosocial es/Other Cost savings and spiritual Health Care driven by hospital support, end- Providers readmission costs of-life plan- Communica- ($6,421 versus ning, and tion Scale $13,275). No dif- post-hospital I: 8.0 (1.4) ference in number care based on C: 7.4 (1.7) of hospital read- patient’s (p<.001) missions only goals. Cost d: .387 number of ICU $1,911/patien admissions. t. Median Days Control: of Hospice Usual hospi- Use: tal care. I: 24 C: 12 Measures: p=.04 6 months post-hospital No difference discharge in proportion of patients who enrolled in hospice.

Percentage with Ad- vanced Direc- tives at Hos- pital Dis- charge: I: 91.1% C: 77.8% (p<.001)

No differences in symptoms, emotional or spiritual support, and quality of life. Brumley et 297 home- Intervention: Percent Very PP: Healthcare al. (2007) bound, termi- In-home in- Satisfied with nally ill pa- terdiscipli- Care: Average Total In-home pal- tients (47% nary pallia- I: 93.4% Cost of Care: liative care cancer, 33% tive care team C: 80.8% I: $12,670 for terminal congestive of physician, (p<.05) (12,523) illnesses heart failure, nurse, and C: $20,222

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness 21% chronic social worker Percent En- (30,026) obstructive and addition- rolled in (p<.001) pulmonary al members Hospice: disease) with a as needed I: 25% Average Cost prognosis of providing C: 36% (per day per pa- ≤1 year to live pain and (NS) tient): plus 1+ hospi- symptom re- I: $95.30 tal or emer- lief and pa- Percent Died C: $212.80 gency de- tient and at Home: (p=.02) partment vis- family educa- I: 71% its in previous tion and C: 51% 12 months. 145 training to (p<.001) in interven- enhance com- tion, 152 in fort, manage control. 75% symptoms, died during and improve study. quality of life aligned with patient’s wishes.

Control: Usual care.

Measures: 90 days Engelhardt 186 patients Intervention: Patient Satis- PP: Healthcare et al. (2006) and 143 sur- Advanced faction Post- rogate deci- Illness Coor- Treatment: Average Advanced sion-makers dinated Care I: 4.07 (.68) Healthcare Illness Coor- with advanced Program de- C: 3.98 (.67) Costs Per Pa- dinated Care serious illness livered by al- (p=.03) tient: Program (chronic ob- lied health d: .18 I: $12,123 (AICCP) structive pul- personnel C: $16,295 monary dis- (e.g., nurses, Reported (NS) ease, chronic social work- Problems by heart failure, ers) to im- Surrogates: d: .18 cancer). For prove care for I: .41 (.30) patients, 86 in patients cop- C: .53 (.32) intervention, ing with ad- (p=.03) 100 in control. vanced illness d: 39 For surro- preparing for gates, 67 in end-of-life Percentage intervention, care includ- Completed 76 in usual ing physician Advanced care. 169 with support, Directive(s):

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness cost data, 93 in health litera- I: 69.4% intervention, cy, and care C: 48.4% 76 in control. coordination (p=.006) over 6 sessions. Cost Mean Num- $452/patient. ber of Ad- vanced Direc- Control: tives: Usual care. I: 1.33 (.98) C: .93 (1.07) Measures: (p=.01) 6 months Hughes et al. 1,966 patients Intervention: Statistically PP: Healthcare (2000) (188 terminal, Team- significant dif- 906 non- managed ferences ob- Total Costs: Team- terminal) with home-based served between I: $31,401 managed 2+ impair- primary care groups on: (32,624) home-based ments in activ- including a Health- C: $28,008 primary care ities of daily primary care Related Qual- (30,613) for impaired living, termi- manager, 24- ity of Life (for (p=.005) or terminally nal illness, hour contact terminal pa- ill patients congestive for patients, tients only), Total VA Costs: heart failure, prior approv- including I: $25,614 or chronic ob- al of hospital - Role func- (27,339) structive pul- readmissions, tion-emotional C: $21,687 monary dis- home-based - Social func- (25,709) ease and 1,883 primary care tion (p<.001) caregivers physician, - Bodily pain across 16 Vet- and team par- - Mental health Total Non-VA erans Affairs ticipation in - Vitality Costs: (VA) centers. discharge - General I: $5,787 (17,172) >90% male. planning for health C: $6,321 981 in inter- as long as (13,210) vention, 985 in needed until Satisfaction (p<.001) control. maximum with Care (for patient bene- non-terminal fit was patients on- achieved or ly), including different level - Access of care re- - Technical quired. 78% quality used services. - Communica- tion Control: - Interpersonal Standard care - Outcomes (Veterans Af-

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness fairs and pri- Health- vate sector). Related Qual- ity of Life (for Measures: caregivers) 12 month follow-up Satisfaction with Care (for caregivers) Burden (for caregivers of non-terminal patients)

Proportion Readmitted: I: 61.2% C: 63.3% (NS)

LIMITATIONS AND FUTURE DIRECTIONS Existing reviews highlight methodological concerns that limit the ability to draw meaningful cost-effectiveness conclusions from current data. Moreover, there are some aspects of end-of-life care that make economic analyses particularly complex. Most broadly, it is unclear whether standard cost-effectiveness methodology (i.e. QALYs) is appropriate for end-of-life care, since end-of-life care focuses on maximizing additional years of healthy life rather than the quality of dying and death. Overall, both clinical efficacy (for whichever outcomes matter most) and cost-effectiveness may differ depending on different types of patients (e.g., how much time left to live) and different types of illnesses (e.g., cancer versus dementia). At this stage of life, individual patients with serious illnesses, frequent multimorbidity, and differing end-of-life concerns have a complex set of needs that can lead to vastly different costs.

Almost all studies compare palliative care interventions to usual care but not to each other to ascertain whether certain elements are more or less cost-effective. Palliative care interventions appear to vary significantly in terms of both resource and time intensity, which could lead to vastly different efficacy and costs. Similarly, consistent end-of-life outcomes are not measured across studies, making it difficult to draw overarching conclusions. Almost all studies focus on healthcare costs rather than broader societal costs, which may be in part because it is too difficult to assess out-of-pocket and indirect costs for patients and informal caregivers. Related, while caregivers are included in some palliative care interventions, cost-effectiveness data for caregiver outcomes are limited. In cases where interventions improve outcomes for both patients and caregivers, a combined measure of cost-effectiveness may reveal more robust savings.

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There is a high likelihood that patients receiving end-of-life care also receive additional care by other providers outside the purview of the study, making it difficult to attribute cost-effectiveness to any one intervention. Another issue is that palliative care may be perceived as less profitable than more aggressive treatment options for any individual facility that receives insurance reimbursements. On the other hand, the growth in private hospice facilities raises opposing concerns of enrolling too many patients in hospice care before they need or would benefit from the services. To address these types of concerns, studies would benefit from assessing costs and outcomes across the entire healthcare system rather than limited to any specific health services.

Policy changes will need to ensure that healthcare providers are adequately mo- tivated and compensated for palliative care services outside of study settings but also regulated to ensure the services are being provided for their intended purposes. Even if cost-effective, some argue a new financing system remains a pre- requisite to making hospice care accessible and affordable. Clearly, much remains to be studied in order to truly understand the potential cost-savings of palliative care for both the healthcare system and society at large (Murtagh et al., 2013; Smith et al., 2014; Dzingina & Higginson, 2015; Raphael et al., 2001).

SUMMARY Most palliative care interventions do not improve clinical outcomes or delay mortality (i.e. how long the patient will live), but do improve other outcomes of greater priority near end-of-life (e.g., patient satisfaction, mood, quality of life, completion of advanced directives, dying in preferred location). Hospice care studies lack randomized trials, but demonstrate the above benefits with mixed cost findings. A recent analysis of Medicare data found hospice care cost significantly more than it saved in hospital costs compared to usual care; however, an analysis limited to poor-prognosis cancer patients found hospice care to be cost- saving. Palliative care also demonstrates the above benefits and incurs similar or lower resource use and associated costs compared to usual care, thus suggesting cost-effectiveness in terms of those metrics.

KEY POINTS Nurse-Led Follow-Up Interventions • Nurse-based coordination services for patients with terminal cancer were 41% less expensive than standard care per patient. • Nurse-led monthly follow-up with information, support, and coordination for patients with lung cancer increased patient satisfaction without any difference in costs compared to conventional medical follow-up. • A nurse-led phone-based psychoeducational intervention for patients with new diagnosis of advanced cancer improved quality of life and mood without increasing healthcare utilization compared to usual oncology care over three years.

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Interdisciplinary Specialist Team Interventions • A interdisciplinary specialist team coordinated-care program for end-of-life for patients with advanced serious illness increased patient satisfaction and completion of advanced directives and decreased surrogate decision-maker problems with a trend toward lower costs compared to usual care after six months. • Interdisciplinary specialist teams for hospital patients with life-limiting illnesses increased patient satisfaction, days of hospice use, and completion of advanced directives and cost significantly less than usual hospital care six months post-discharge. • Interdisciplinary specialist team contacts for patients with multiple sclerosis and their caregivers saved costs per patient compared to usual care after three months. • Interdisciplinary specialist teams for home-bound terminally ill patients and their families had significantly higher patient satisfaction and significantly lower costs after three months. • A interdisciplinary specialist team home-based primary care program in the Veterans Health Administration (VHA) improved quality of life in nonterminal patients and patient satisfaction in terminal patients but was significantly more expensive than standard care after 12 months. • Overall, typical nurse-led or team-based end-of-life interventions for patients with late-stage cancer or otherwise clearly at end-of-life appear to have benefits with reduced or equal costs. More studies are needed to understand the cost-effectiveness of these interventions for patients with other conditions or longer horizons for continued life.

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Bakitas M, Lyons KD, Hegel MT, Balan S, Brokaw FC, Seville J, Hull JG, Li Z, Tosteson TD, Byock IR, Ahles TA. Effects of a palliative care intervention on clinical outcomes in patients with advanced cancer: the Project ENABLE II randomized controlled trial. JAMA. 2009 Aug 19;302(7):741-9.

Boni-Saenz AA, Covinsky KE, Moody SY. The Economic Burden of End-of-Life Illness. In Eds. Emanuel LL, Librach, SL. Palliative Care: Core Skills and Clinical Competencies, 2nd Edition. Elsevier Health Sciences, 2011.

Brumley R, Enguidanos S, Jamison P, Seitz R, Morgenstern N, Saito S, McIlwane J, Hillary K, Gonzalez J. Increased satisfaction with care and lower costs: results of a randomized trial of in-home palliative care. J Am Geriatr Soc. 2007 Jul;55(7):993-1000.

Capurro D, Ganzinger M, Perez-Lu J, Knaup P. Effectiveness of eHealth interventions and information needs in palliative care: a systematic literature review. J Med Internet Res. 2014 Mar 7;16(3):e72.

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Dzingina MD, Higginson IJ. Public Health and Palliative Care in 2015. Clin Geri- atr Med. 2015 May;31(2):253-263.

Engelhardt JB, McClive-Reed KP, Toseland RW, Smith TL, Larson DG, Tobin DR. Effects of a program for coordinated care of advanced illness on patients, surrogates, and healthcare costs: a randomized trial. Am J Manag Care. 2006 Feb;12(2):93-100. Gade G, Venohr I, Conner D, McGrady K, Beane J, Richardson RH, Williams MP, Liberson M, Blum M, Della Penna R. Impact of an inpatient palliative care team: a randomized control trial. J Palliat Med. 2008 Mar;11(2):180-90.

Gomes B, Calanzani N, Curiale V, McCrone P, Higginson IJ. Effectiveness and cost-effectiveness of home palliative care services for adults with advanced illness and their caregivers. Cochrane Database Syst Rev. 2013 Jun 6;6:CD007760.

Gomes B, Calanzani N, Higginson IJ. Benefits and costs of home palliative care compared with usual care for patients with advanced illness and their family caregivers. JAMA. 2014 Mar 12;311(10):1060-1.

Gozalo P, Plotzke M, Mor V, Miller SC, Teno JM. Changes in Medicare costs with the growth of hospice care in nursing homes. N Engl J Med. 2015 May 7;372(19):1823-31.

Higginson IJ, McCrone P, Hart SR, Burman R, Silber E, Edmonds PM. Is short- term palliative care cost-effective in multiple sclerosis? A randomized phase II trial. J Pain Symptom Manage. 2009 Dec;38(6):816-26.

Hughes MT, Smith TJ. The growth of palliative care in the United States. Annu Rev Public Health. 2014;35:459-75.

Hughes SL, Weaver FM, Giobbie-Hurder A, Manheim L, Henderson W, Kubal JD, Ulasevich A, Cummings J; Department of Veterans Affairs Cooperative Study Group on Home-Based Primary Care. Effectiveness of team-managed home- based primary care: a randomized multicenter trial. JAMA. 2000 Dec 13;284(22):2877-85.

May P, Normand C, Morrison RS. Economic impact of hospital inpatient palliative care consultation: review of current evidence and directions for future research. J Palliat Med. 2014 Sep;17(9):1054-63.

Moore S, Corner J, Haviland J, Wells M, Salmon E, Normand C, Brada M, O'Brien M, Smith I. Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial. BMJ. 2002 Nov 16;325(7373):1145.

Murtagh FE, Groeneveld, IE, Kaloki YE, Calanzani N, Bausewein C, Higginson IJ. Capturing activity, costs, and outcomes: the challenges to be overcome for successful economic evaluation in palliative care. Prog Palliat Care. 2013 Sep; 21(4):232-235.

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Obermeyer Z, Makar M, Abujaber S, Dominici F, Block S, Cutler DM. Association between the Medicare hospice benefit and health care utilization and costs for patients with poor-prognosis cancer. JAMA. 2014 Nov 12;312(18):1888-96.

Powers BW, Makar M, Jain SH, Cutler DM, Obermeyer Z. Cost savings associated with expanded hospice use in medicare. J Palliat Med. 2015 May;18(5):400-1. Raftery JP, Addington-Hall JM, MacDonald LD, Anderson HR, Bland JM, Cham- berlain J, Freeling P. A randomized controlled trial of the cost-effectiveness of a district co-ordinating service for terminally ill cancer patients. Palliat Med. 1996 Apr;10(2):151-61.

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CHAPTER 19: OTHER SELECTED MEDICAL DISORDERS

ABSTRACT A growing body of evidence demonstrates the clinical importance of integrating behavioral and medical care, but limited economic data exist on behavioral interventions for biomedical conditions. Behavioral interventions can contribute to primary or secondary prevention (i.e. delay of onset or relapse), alleviate specific symptoms, provide psychosocial support, and improve administration of or adherence to treatments. Given the paucity of cost-effectiveness studies to date, findings for several biomedical conditions are combined although generalizability remains uncertain, as most are specific to a single condition.

For prevention of acute respiratory infection, Mindfulness Meditation may be more cost-effective than moderate intensity exercise, and both are more cost- effective than a waiting list. For alleviating significant fatigue in patients with multiple sclerosis, Cognitive Behavioral Therapy (in-person or via the Internet) may be cost-effective for alleviating fatigue, depending on the willingness to pay thresholds, but is not for improving QALYs compared to standard care. For alleviating urinary incontinence in older adults in nursing homes, Behavioral Train- ing Therapy may be cost-effective over longer time intervals, when training costs may be offset by costs saved in supplies. For psychosocial support in cancer, a supportive-expressive support group for women with metastatic breast cancer may be more cost-effective than standard care for improving psychological distress and pain, depending on the willingness to pay thresholds, and a stress management program for cancer patients undergoing chemotherapy may be cost-effective if self-administered but not if professionally administered. For improving treatment in patients with periodontitis, an individually-tailored cognitive behavioral oral health education program had the potential to be more cost- effective than the standard oral hygiene program. For improving antiretroviral medication adherence in HIV-positive patients, Motivational Interviewing-based Cognitive Behavioral Therapy with or without modified Directly Observed Therapy was less cost-effective than usual care. For reducing serious medication errors by providers, a pharmacist-led technology-based informational intervention (i.e. Academic Detailing) seemed more cost-effective than computer- generated feedback.

Overall, these data suggest the role that behavioral interventions may play in improving care and reducing costs for a myriad of biomedical conditions.

BACKGROUND ON BIOMEDICAL CONDITIONS Broadly, biomedical conditions are those that focus on any diseases of the body, ranging from periodontal diseases to infectious diseases to cancers. While behavioral interventions are often considered integral to managing or treating neuropsychiatric conditions, they are typically considered secondary interventions for biomedical conditions. First-line responses are more often medications or medical procedures (e.g., surgery); however, behavioral interventions have the potential to help prevent onset, manage symptoms, and improve outcomes.

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Given the paucity of data, this chapter combines available findings for behavioral interventions in biomedical conditions that did not fit elsewhere. While prevalence, economic burden, and effective interventions may vary for each condition, this initial overview reveals the potential cost-effectiveness of behavioral interventions for some biomedical conditions.

COST-EFFECTIVENESS OF INTERVENTIONS Within the limitations of available data, we present findings for behavioral interventions across different biomedical conditions focused on prevention, allevia- tion of specific symptoms, psychosocial management of biomedical treatments, and improvement of administration of and adherence to biomedical treatments.

Prevention Interventions One cost-effectiveness study investigated preventing onset of a biomedical condition. Available treatments for acute respiratory infection (i.e. viral infections that prevent normal breathing) are not very effective, making prevention an even higher priority. Some evidence suggests that enhancing general mental and physical health may reduce these infections (Barrett et al., 2012). In adults over the age of fifty, both Mindfulness Meditation (a psychosocial intervention) and moderate intensity exercise (a physical activity intervention) reduced incidence of acute respiratory infection over a waiting list after 14 weeks (41% in meditation, 35% in exercise, 55% in waiting list). Notably, Mindfulness Meditation directly targets the mind-body connection by trying to increase awareness of bodily sensations, thoughts, and emotions and promote a more positive mind-body response to stress. This meditation had the lowest health-related costs ($65 versus $136 in exercise and $214 in waiting list), but did not include intervention costs (~$450), which indicate cost offset would not occur in this short time interval. Between the two, researchers concluded Mindfulness Meditation had greater cost-benefit than moderate intensity exercise, but it appears both interventions need to be assessed over longer time intervals (Rakel et al., 2013). Notably, both interventions may be expected to have additional health benefits, and thus impact on other health outcomes should also be assessed in future or follow-up studies.

Table 1. Behavioral Interventions for Prevention of Biomedical Conditions Cost Method and Clinical Study Participants Effective- Intervention Outcomes ness Rakel et al. 149 adults Interventions: Percent with PP: Societal (2013) (age 50+ (1) Mindful- Acute Respirato- years) with ness Medita- ry Infection: Total Health- Meditation prior acute tion training I1: 41% Related Cost or exercise respiratory for eight I2: 35% (per adult): for prevent- infection. 51 in weekly 2.5- C: 55% I1: $65 (120) ing acute intervention hour sessions. I2: $136 (293) respiratory #1, 47 in in- (2) Moderate Mean Global Se- C: $214 (416) infection tervention #2, intensity ex- verity: (MEPARI) 51 in control. ercise class I1: 144 (95% CI, Does not in-

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Cost Method and Clinical Study Participants Effective- Intervention Outcomes ness for eight 62 to 225) clude inter- weekly 2.5- I2: 248 (95% CI, vention costs hour sessions. 77 to 419) of approx. C: 358 (95% CI, $450. Control: 221 to 495) Waiting list. Mean Illness Measures: Days Due to 14 weeks Acute Respirato- ry Illness: I1: 5.04 (95% CI, 2.25 to 7.83) I2: 5.13 (95% CI, 2.64 to 7.62) C: 8.89 (95% VI, 5.76 to 12.02)

Symptom-Specific Interventions Some behavioral interventions target specific symptoms of biomedical conditions. Other interventions focus less on alleviating symptoms, but instead target preventing onset or progression, improving treatment adherence, or accelerating recovery outcomes. As one example, the chapter on Depressive Disorders (Chapter 2) includes a section on behavioral interventions targeting depressive symptoms in persons with co-occurring biomedical conditions. These studies are not repeated here, but are conceptually similar to studies of fatigue and incontinence discussed below.

Fatigue in Multiple Sclerosis As another example, fatigue is one of the most common and debilitating symptoms associated with multiple sclerosis. Although this symptom is related to the biomedical condition, the precise cause remains unknown. Similar to Chronic Fa- tigue Syndrome (see Chapter 15), interventions focus on managing the symptom rather than eliminating it. Two cognitive behavioral interventions in the United Kingdom (one in-person, one Internet-based) for significant fatigue in persons with multiple sclerosis might be cost-effective at improving fatigue, depending on the willingness to pay thresholds, but were dominated in terms of quality of life.

First, an in-person group-based cognitive behavioral management program significantly improved global fatigue severity (40% of persons versus 19% in standard care) after four months. The intervention cost £2,157 per person with clinically significant improvement in fatigue or £1,259 per incremental improvement in fatigue, both of which depend on the willingness to pay thresholds. However, it was dominated in terms of QALYs (Thomas et al., 2013). Second, an Internet- based self-management program (MS Invigor8) with tailored, interactive sessions

423 Selected Medical Disorders and optional phone support significantly improved fatigue, anxiety, and depression compared to standard care immediately post-treatment. Similar healthcare costs to standard care suggest cost-effectiveness in improving fatigue and mental health, even though there were no differences in QALYs (Moss-Morris et al., 2012).

Urinary Incontinence in Older Age Urinary incontinence in older age can often be a side effect of a biomedical condition or its treatment. The economic impact of this incontinence in nursing homes is about $2 billion annually or at least 10% of all nursing home care costs (Hu, 1986). Thus, an effective intervention to reduce urinary incontinence in nursing homes could lead to substantial cost savings. Behavioral Training Therapy, including prompts for scheduled hourly toilet use and social reinforcement (e.g., praise) for appropriate toileting behavior, cost $5 per patient per day and reduced incontinence-related supply costs by about $0.50 per patient per day immediately post-treatment. It would take ten days of continence maintenance to recover the costs of one day of training, but there was only a marginal change in daily wet episodes (1.72 in intervention versus 2.21 in usual care). For example, a 13-week training period would require 130 weeks (2.5. years) to recover the entire costs. Notably, quality of life improved significantly, which has other cost- benefits that could also be assessed (Hu et al., 1999).

Table 2. Behavioral Interventions for Specific Symptoms of Biomedical Conditions Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Thomas et al. 164 patients Intervention: Fatigue As- PP: Healthcare (2013) with multiple Group-based sessment In- and Social Ser- sclerosis and (4-11 people) strument – vices Group-based significant fa- cognitive be- Global Fa- fatigue man- tigue in UK. havioral and tigue Severity ICER (per addi- agement 84 in interven- energy effec- (GFS): tional person program for tion, 80 in con- tiveness pro- I: 5.26 (1.03) with clinically multiple trol. gram for six C: 5.66 (.93) significant im- sclerosis 90-minute d: .408 provement in (Fatigue: sessions plus fatigue): Applying current local Multiple Scle- £2,157 Cognitive practice. Es- rosis-Fatigue behavioral timated cost Self-Efficacy: ICER (per 1- and Energy £453/patient. I: 56 (19) point improve- effectiveness C: 53 (17) ment in GFS): Techniques Control: d: .167 £1,259 to lifeStyle, Current local FACETS) practice. Multiple Scle- ICER (per rosis Impact QALY): Measures: Scale-29: Dominated 4-month fol- I: 44.9 (19.2) low-up C: 43.0 (17.3) No significant d: .104 differences in

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Percent Clini- QALYs, so corre- cally Signifi- sponding ICER cant Im- not calculated but provement: as intervention is I: 40% more expensive C: 19% can assume usual (p=.009) care dominated. Moss-Morris 40 patients Intervention: Fatigue Scale: PP: Healthcare et al. (2012) with multiple Cognitive I: 12.39 (6.84) (excluding med- sclerosis and Behavioral C: 19.57 (5.20) ication) Internet- significant fa- Therapy self- (p<.001) based Cogni- tigue in UK. management d: 1.193 Total Mean tive Behav- 23 in interven- program (MS Costs: ioral Thera- tion, 17 in con- Invigor8) Modified Fa- I: £2007-2008211 py self- trol. with 8 tai- tigue Impact (299) management lored, interac- Scale: C: £2007-2008214 program for tive sessions I: 9.00 (3.75) (239) multiple and up to 30- C: 12.88 (3.89) sclerosis fa- 60-minute (p<.001) Mean QALY tigue phone sup- d: 1.016 Gain*: port sessions I: .1212 for 8-10 Hospital C: .1243 weeks. Anxiety and (p=.038) Depression Control: (HADS): *Due to differ- Standard Anxiety sub- ences at baseline, care. scale QALY gain 0.015 I: 6.44 (3.91) higher in inter- Measures: C: 11.65 (5.26) vention. Post- (p<.001) treatment (10 d: 1.136 Willingness to weeks). pay threshold: Depression For standard subscale threshold of I: 5.18 (3.38) £20K/QALY, C: 7.73 (3.62) intervention (p<.001) costs cannot ex- d: 1.014 ceed £300/ person or ~£50/ session. More widespread use or maintaining gains beyond 10 weeks would offset costs to greater extent.

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Hu et al. 133 inconti- Intervention: Daily Aver- PP: Supplies (1990) nent elderly Behavioral age of Patient females (age Training Requests (to Supply Costs Training in- 65+ years; 90% Therapy in- use toilet out- (per day): continent el- 80+ years) liv- cluding side sched- I: $1.29 derly in ing in nursing prompts for uled inter- C: $1.86 nursing homes. 72 in scheduled vals): homes intervention, hourly toilet I: 1.45 Quality of Life 71 in control. use and social C: 1.21 (EQ-5D): reinforcement I: .71 (.28) (e.g., praise) C: .62 (.27) for appropri- Daily Aver- (p=.038) ate toileting age of Wet behavior for 3 Episodes: It costs about months. Ap- I: 1.72 $5/patient/day to prox. costs C: 2.21 reduce supply $5/patient/d costs about ay. Percent Im- $0.50/patient/day, provement so it would take Control: (in last month 10 days of conti- Usual care. of implemen- nence mainte- tation): nance to recover Measures: I: 26% the cost of 1 day 22-week fol- C: 8% of training. low-up

Psychosocial Management Interventions Biomedical conditions and life-threatening health challenges can cause substantial distress, stress, and anxiety in patients. Both physiological and behavioral reactions to stress and anxiety can contribute to negative health outcomes and increase healthcare costs. For example, fears about the meaning of experienced pain may increase pain severity and pain-related disability (Zale et al., 2013). Stress and anxiety may also negatively influence healthcare decisions or self-care; stress may encourage impulsive or short-term decision-making that may not be ideal for longer-term disease outcomes, and anxiety may drive avoidance behaviors that could impair treatment adherence.

Behavioral interventions like psychosocial support groups and stress management techniques are designed to reduce stress and anxiety and thereby improve overall management of the biomedical condition. A systematic review for self- management interventions found that they reduced healthcare utilization and thus associated costs while maintaining meaningful effects on health outcomes. The researchers concluded that the evidence was strongest for respiratory and cardiovascular disorders, and that more research could assess which components of self-management were most effective (Panagioti et al., 2014).

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A few interventions target psychosocial factors for cancer patients. One study specifically looked at cancer patients with high levels of anxiety (see Chapter 1 on Anxiety Disorders). Included here, one study looked at women with breast cancer and another at cancer patients beginning chemotherapy. For women with metastatic breast cancer in Canada, adding a psychosocial supportive-expressive support group to standard care reduced psychological distress and pain more than standard care alone after about two years with no significant differences in total healthcare costs. The supportive-expressive support group may be cost- effective at CN$5,550 per 0.5-increase in effect size in psychological distress and CN$4,309 per 0.5-increase in effect size for pain, depending on the willingness to pay thresholds for these metrics (Lemieux et al., 2006).

For cancer patients (58% breast cancer, 21% lung cancer) about to undergo intravenous chemotherapy without radiation for the first time, adding a stress management program including abdominal breathing, progressive muscle relaxation with guided imagery, and coping self-statements to usual psychosocial care may be more cost-effective than usual psychosocial care alone, depending on how it was administered. A professionally-administered version with a single in-person session did not differ from usual care and cost $136 per patient, while a self- administered version with a videotape, audiotape, and booklet was more effective than usual care at improving mental wellbeing and only cost $73 per patient (Jacobsen et al., 2002).

Table 3. Behavioral Interventions for Psychosocial Management Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Lemieux et 125 women Intervention: Change in PP: Healthcare al. (2006) with metastat- Psychosocial Profile of ic breast can- supportive- Mood States Total Healthcare Group psy- cer across 7 expressive – Total Mood Costs (per pa- chosocial centers in support Disturbance tient): therapy in Canada. 82 in group (6-10 (POMS- I: CN$2002- women with intervention, participants) TMD): 0331,715 metastatic 43 in control. for weekly 11.5 C: CN$2002- breast cancer 90-minute d: .32 0328,189 sessions plus (NS) standard Change in care. Average Pain Visual ICER (per 0.5

cost CN$2002- Analog Scale effect size in 0355.46/patien (VAS): 0.9 POMS-TMD): t/session. d: .40 CN$2002-035,550

Control: ICER (per 0.5 Standard effect size in care. VAS):

CN$2002-034,309 Measures: 722-750 days

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Jacobsen et 382 patients Intervention: Group by time PP: Societal al. (2002) with cancer (1) Profes- interactions about to start sionally- compared to Incremental Stress man- intravenous administered control: Cost of Inter- agement chemotherapy stress man- vention (per pa- training for (without radi- agement Medical Out- tient): cancer pa- ation therapy) training in- comes Study I1: $200073 tients under- for the first cluding ab- 36-Item Short I2: $2000136 going chem- time at one dominal Form (SF-36) otherapy cancer center breathing, Mental Sum- in U.S. 119 in progressive mary intervention muscle relax- (1): NS #1, 131 in in- ation with (2): p<.01 tervention #2, guided im- Physical sum- 132 in control. agery, and mary 58% breast coping self- (1): NS cancer, 21% statements in (2): NS lung cancer, one 60- 5% ovarian minute ses- Center for cancer, 4% sion. Epidemiolog- lymphoma, (2) Patient ical Studies 3% colon can- self-admini- Depression cer, 2% pros- stered stress Scale tate cancer, 2% management (1): NS endometrial training via (2): p<.01 cancer. package of instructional State-Trait resources in- Anxiety In- cluding 15- ventory— minute vide- State Scale otape and 12- (1): NS page booklet (2): p<.05 about coping with chemotherapy and 35-minute audiotape about active relaxation.

Control: Usual psychosocial care.

Measures:

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Before each chemotherapy cycle (minimum 7 days) for 4 times total.

Treatment Delivery and Adherence Interventions Some behavioral interventions focus on improving treatment delivery, increasing treatment adherence, or reducing medication errors, with studies ranging from periodontal disease to HIV and AIDS.

For patients with moderate to advanced periodontitis (i.e. serious gum disease)— which can both be caused in part by certain biomedical conditions and be an increased risk factor for other ones—poor dental hygiene is a major contributor. In Sweden, an individually tailored oral health education program based on cognitive behavioral strategies had the potential to be more cost-effective than the standard oral hygiene program. After one year, more patients in the individually-tailored intervention (61% versus 34% in the standard program) met criteria for treatment success (i.e. at least two of three criteria for pocket closure, bleeding on probing, and plaque index; each criteria must be in the highest tier of improvement with none in lowest tier). These improvements cost an additional €191 per successful case, which would depend on the willingness to pay threshold for this metric (Jönsson et al., 2012; Jönsson et al., 2010).

For HIV-positive patients receiving antiretroviral therapy—a combination of multiple medications to improve HIV-related health outcomes—consistent adherence is critical relative to other treatment regimens. Poor adherence to antiretroviral therapy risks permanently impacting the efficacy of both current and future treatments for that patient. While Motivational Interviewing (MI)-based Cognitive Behavioral Therapy (CBT) with or without modified Directly Ob- served Therapy (mDOT) was designed to improve treatment adherence, neither version had any improvements over standard care after 48 weeks. Although the total costs per patient were not significantly different either ($1,018 for MI-based CBT alone and $1,309 for MI-based CBT plus mDOT compared to $881 for standard care), the lack of improvements in treatment adherence suggest there is no additional cost-effectiveness at this time (Rasu et al., 2013; Goggin et al., 2013).

While the prior intervention targeted treatment adherence, another intervention in the United Kingdom targeted reducing serious medication errors by providers via a pharmacist-led technology-based informational intervention (i.e. Academic Detailing; all doctors encouraged to attend with at least one member of nursing staff, at least one member of reception staff, and practice manager) including educational outreach to the providers, feedback, and dedicated support for twelve weeks.. The three medication errors were prescribing NSAIDs (non-selective non-steroidal anti-inflammatory drugs) without PPIs (proton-pump inhibitors)

429 Selected Medical Disorders for persons with a history of peptic ulcer, prescribing beta blockers for persons with asthma, and prescribing ACE (angiotensin converting enzyme) inhibitors or diuretics in persons older than 75 years without urea and electrolytes measurements in the preceding 15 months. After 12 months, patients were significantly less likely to have a prescription or monitoring error compared to computer- generated feedback, and only cost £67 per error avoided. If the value were £85 per error avoided, the pharmacist-led intervention has 95% likelihood of being more cost-effective (Avery et al., 2012).

Table 4. Behavioral Interventions for Treatment Adherence of Biomedical Conditions Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness Jönsson et al. 113 patients Intervention: Percentage PP: Societal (2012) with moderate Individually Achieving to advanced tailored oral Pre-Set Crite- Individually periodontitis health educa- ria for Treat- ICER (per suc- tailored oral in non- tion program ment Success: cessful case): health edu- surgical based on I: 61.4% SEK20071,724 cation pro- treatment in cognitive be- C: 33.9% (€2007191.09) gram for per- Sweden. 57 in havioral iodontitis intervention, strategies in- (ITOHEP) 56 in control. cluding Mo- tivational and integrated into non- surgical treatment.

Control: Standard oral hygiene program.

Measures: 12-month follow-up Rasu et al. 204 HIV- Interventions: % Doses Tak- PP: Healthcare (2013) & positive par- (1) Motiva- en: Goggin et al. ticipants re- tional Inter- I1: 69.3% Total Costs (per (2013) ceiving an- viewing- (32.6) patient): tiretroviral based Cogni- I2: 64.6% I1: $1,018 Motivation- therapy in tive Behav- (34.4) I2: $1,309 Interview- U.S. All partic- ioral Thera- C: 75.5% C: $881 ing-based ipants given py) for ten (29.7) Cognitive electronic 25-minute Behavioral drug monitor sessions (6 in % Doses Tak- Therapy in- to track ad- person, 4 by en on Time: tervention herence dur- phone) for 24 I1: 56.9%

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness with or ing study. 70 weeks. Aver- (34.1) without in intervention age cost I2: 52.0% modified Di- #1, 69 in in- $137/patient. (34.1) rectly Ob- tervention #2, (2) 1 plus C: 58.1% served Ther- 65 in control. modified Di- (32.5) apy for an- rectly Ob- tiretroviral served Ther- % Patients therapy ad- apy with dai- HIV-1 RNA herence ly visits/calls <400 cop- (MOTIV8) to observe ies/ML: medication I1: 80.0% (45) ingestion for I2: 66.7% (48) 16 weeks, ta- C: 73.8% (42) pered for weeks 17-24. Average additional cost, $291/patient.

Control: Standard care (includes adherence counseling).

Measures: 48 weeks Avery et al. 72,072 patients Intervention: Percent with PP: Intervention (2012) at-risk for po- Pharmacist- History of tentially seri- led, technol- Peptic Ulcer ICER (per error Pharmacist- ous medica- ogy-based Prescribed avoided): led infor- tion errors information NSAID £66.53 (25th to mation in- across 72 prac- intervention Without PPI: 95.7th percentile, tervention tices in the with feed- I: 3% 66.8 to 81.5) for medica- UK. 36 prac- back on high- C: 4% tion errors tices (34,413 risk prescrib- Willingness to (PINCER) patients) in ing, educa- Percent with pay threshold: intervention tional out- Asthma Pre- If value is #1, 36 practic- reach (i.e. Ac- scribed a £85/error es (37,659 pa- ademic De- Beta Blocker: avoided at 12 tients) in con- tailing), and I: 3% months, 95% trol. clinical sup- C: 3% probability port for 12 pharmacist-led weeks. Aver- Percent ≥75 technology- age cost Years With- based infor- £1,096.09/pra out Urea and mation interven-

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Method and Clinical Cost Study Participants Intervention Outcomes Effectiveness ctice. Electrolytes tion more cost- Measure- effective than Control: ments in ≤15 computer- Computer- Months Pre- generated feed- generated scribed ACE back. feedback for Inhibitor or high-risk Diuretics: medication I: 6% errors and C: 8% educational information for 12 weeks. Average cost £139.26/pract ice.

Measures: 12-month follow-up

LIMITATIONS AND FUTURE DIRECTIONS Clearly, biomedical conditions and their optimal treatments vary immensely, leading to different clinical outcomes and associated costs. In most cases, specific biomedical interventions are necessary. Nonetheless, cognitive and behavioral interventions may be able to augment these treatments, for example by targeting risk factors to prevent disease onset or relapse; reducing or managing specific symptoms; providing psychological support to reduce distress, stress and anxiety; or improving treatment or adherence and clinical decision-making to increase quality of life, improve treatment outcomes, or decrease disability. While early studies suggest these interventions are promising for improving clinical outcomes and reducing costs to the healthcare system, more research is needed to assess the different types of interventions for the different biomedical conditions. Unfortunately, limited cost-effectiveness data make it impossible to generalize findings at this time. Hopefully they provide the impetus for future studies and encourage further development and consideration of behavioral interventions to improve outcomes for biomedical conditions.

KEY POINTS Generalizability of findings is difficult since most behavioral interventions are limited to a single biomedical condition and have not yet been tested for cost- effectiveness across multiple types of biomedical conditions.

Prevention Interventions • For preventing incidence of acute respiratory infection in adults over the age of 50, both Mindfulness Meditation and moderate intensity exercise were

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more cost-effective than usual care after 14 weeks; Mindfulness Meditation may also be more cost-effective than moderate intensity exercise.

Symptom-Specific Interventions • For alleviating significant fatigue in patients with multiple sclerosis, Cogni- tive Behavioral Therapy (CBT) may be more cost-effective than standard care at improving fatigue, but was less cost-effective than standard care at improving quality of life. Both in-person group-based CBT and an internet-based CBT self-management program may be cost-effective. • For alleviating urinary incontinence in older adults in nursing homes, Behav- ioral Training Therapy may offset its own intervention costs over longer time intervals. Full cost offset would require ten days of continence maintenance per day of training.

Psychosocial Management Interventions • For psychosocial support in women with metastatic breast cancer, a supportive-expressive support group may be cost-effective for reducing psychological distress and pain after about two years. • For psychosocial support in cancer patients about to undergo intravenous chemotherapy for the first time, a stress management program was more cost-effective self-administered via a videotape, audiotape, and booklet than via a single professionally-administered session.

Treatment Delivery and Adherence Interventions • For improving treatment in patients with moderate to advanced periodontitis, an individually tailored cognitive behavioral oral health education program had the potential to be more cost-effective than the standard oral hygiene program after 12 months. • For improving antiretroviral medication adherence in HIV-positive patients, Motivational Interviewing-based Cognitive Behavioral therapy with or without modified Directly Observed Therapy did not show any clinical improvements with slightly higher costs compared to usual care, suggesting no additional cost-effectiveness. • For reducing serious medication errors by providers, a pharmacist-led technology-based informational intervention (i.e. Academic Detailing) had the potential to be more cost-effective than computer-generated feedback at £67 after 12 months.

REFERENCES Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, Elliott RA, Howard R, Kendrick D, Morris CJ, Prescott RJ, Swanwick G, Franklin M, Putman K, Boyd M, Sheikh A. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. 2012 Apr 7;379(9823):1310-9.

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Barrett B, Hayney MS, Muller D, Rakel D, Ward A, Obasi CN, Brown R, Zhang Z, Zgierska A, Gern J, West R, Ewers T, Barlow S, Gassman M, Coe CL. Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial. Ann Fam Med. 2012 Jul-Aug;10(4):337-46.

Goggin K, Gerkovich MM, Williams KB, Banderas JW, Catley D, Berkley-Patton J, Wagner GJ, Stanford J, Neville S, Kumar VK, Bamberger DM, Clough LA. A randomized controlled trial examining the efficacy of motivational counseling with observed therapy for antiretroviral therapy adherence. AIDS Behav. 2013 Jul;17(6):1992-2001.

Hu TW. The economic impact of urinary incontinence. In Clinics in Geriatric Medicine, a monograph. Edited by J. G. Ouslander. University Park, PA, 1986.

Hu TW, Kaltreider DL, Igou JF, Yu LC, Rohner TJ. Cost effectiveness of training incontinent elderly in nursing homes: a randomized clinical trial. Health Serv Res. 1990 Aug;25(3):455-77.

Jacobsen PB, Meade CD, Stein KD, Chirikos TN, Small BJ, Ruckdeschel JC. Effi- cacy and costs of two forms of stress management training for cancer patients undergoing chemotherapy. J Clin Oncol. 2002 Jun 15;20(12):2851-62.

Jönsson B, Ohrn K, Lindberg P, Oscarson N. Cost-effectiveness of an individually tailored oral health educational programme based on cognitive behavioural strategies in non-surgical periodontal treatment. J Clin Periodontol. 2012 Jul;39(7):659-65.

Jönsson B, Ohrn K, Lindberg P, Oscarson N. Evaluation of an individually tailored oral health educational programme on periodontal health. J Clin Periodon- tol. 2010 Oct;37(10):912-9.

Lemieux J, Topp A, Chappell H, Ennis M, Goodwin PJ. Economic analysis of psychosocial group therapy in women with metastatic breast cancer. Breast Can- cer Res Treat. 2006 Nov;100(2):183-90.

Moss-Morris R, McCrone P, Yardley L, van Kessel K, Wills G, Dennison L. A pilot randomised controlled trial of an Internet-based cognitive behavioural therapy self-management programme (MS Invigor8) for multiple sclerosis fatigue. Be- hav Res Ther. 2012 Jun;50(6):415-21.

Panagioti M, Richardson G, Small N, Murray E, Rogers A, Kennedy A, Newman S, Bower P. Self-management support interventions to reduce health care utilisation without compromising outcomes: a systematic review and meta-analysis. BMC Health Serv Res. 2014 Aug 27;14:356.

Rakel D, Mundt M, Ewers T, Fortney L, Zgierska A, Gassman M, Barrett B. Value associated with mindfulness meditation and moderate exercise intervention in acute respiratory infection: the MEPARI Study. Fam Pract. 2013 Aug;30(4):390-7.

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Rasu RS, Malewski DF, Banderas JW, Malomo Thomson D, Goggin K. Cost of behavioral interventions utilizing electronic drug monitoring for antiretroviral therapy adherence. J Acquir Immune Defic Syndr. 2013 May 1;63(1):e1-8.

Thomas S, Thomas PW, Kersten P, Jones R, Green C, Nock A, Slingsby V, Smith AD, Baker R, Galvin KT, Hillier C. A pragmatic parallel arm multi-centre randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based fatigue management programme (FACETS) for people with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Oct;84(10):1092-9.

Zale EL, Lange KL, Fields SA, Ditre JW. The relation between pain-related fear and disability: a meta-analysis. J Pain. 2013 Oct;14(10):1019-30.

435 Delivery Strategies

EPILOGUE: PROMISING HEALTH CARE DELIVERY STRATEGIES TO IMPROVE COST-EFFECTIVENESS OF CARE

INTRODUCTION While individual studies of specific clinical interventions for specific disorders, symptoms or functional outcomes are necessary to determine the most cost- effective approaches for a given clinical population, findings across conditions suggest some common approaches for improving the cost-effectiveness of behavioral interventions for mental health or medical conditions more generally. Here, we examine some of these promising care delivery approaches from a cost- effectiveness perspective. We will describe and explore the rationale for the approach, and provide examples of existing research that demonstrate the potential and limits of these approaches for improving cost-effectiveness of care for behavioral and mental health conditions.

To date, these approaches have centered around two general strategies for improving cost-effectiveness. First, a subset of these interventions improves the efficiency of care delivery to reduce costs. For example, they minimize use of more intensive and expensive treatments by providing them only for patients who do not get better with initial lower cost treatments (e.g., stepped care), or they limit the use of specialists and other higher cost professionals to delivery of complex specialty treatments by having them work alongside generalist care teams that plan and deliver the majority of care (e.g., collaborative care). A second subset of interventions minimizes contact with health professionals while still achieving clinical benefits. These include telehealth and other media-based interventions that provide automated cognitive behavioral skills building training or other behavior change support via the Internet, telephone, or written materials, and peer-led interventions such as mutual help groups. Beneficially, most of these cost-saving interventions also improve clinical outcomes for patients by facilitating proactive care planning and care coordination, increasing patient engagement in therapeutic activities, and expanding the reach of such interventions into the home and community.

Further research on all of these care models is needed to identify optimal health care delivery organization and processes and to identify patient populations and conditions that benefit from use of these models. But consideration of the existing literature provides early indications of successful models and the limitations of each that may help guide design of health care delivery systems more broadly.

APPROACHES TO MAKE HEALTH CARE DELIVERY MORE EFFICIENT Stepped Care Models In stepped care models, patients typically initiate lower intensity treatment and escalate in treatment intensity if and as needed over time based on patient response. Stepped care models have been tested and found to be clinically effective and cost-effective for at least some applications. One common stepped care strategy is to start treatment-seeking patients on a treatment that involves low clinical contact, such as self-management, computer-based therapy

436 Delivery Strategies protocols, or bibliotherapy, with on-going assessment of treatment progress. In cases where patients do not experience significant improvement with the low contact care, more intensive options, such as therapist-led cognitive behavioral therapy, group treatment or medication, may be added. In some cases, even more intensive treatments, such as multidisciplinary specialty treatment programs, are offered to patients who do not show improvement with the initial care enhancement. Variants on this general model include offering stepped care to high risk patients who do not meet diagnostic criteria to try to prevent the development of psychiatric disorders, medication protocols where drug regimens are augmented in treatment-resistant patients, and protocols where the initial level of care consists only of assessment without additional treatment (i.e. watchful waiting).

A relatively large number of trials have examined stepped care for depression. A meta-analysis of 10 clinical trials found a small to medium sized effect (Cohen’s d=.36, 95% CI: .20 -.48) of stepped care on the clinical outcomes of depression relative to treatment as usual (van Straten et al., 2014). However, the authors concluded that specific recommendations for implementation were limited by lack of cost-effectiveness data and variation in stepped care protocols.

Stepped care interventions for anxiety have also shown promising clinical benefits and early evidence of cost-effectiveness. A cluster randomized trial of 43 primary care practices in the Netherlands examined the cost-effectiveness of a collaborative stepped care intervention as compared to primary care treatment as usual in 180 patients with Generalized Anxiety or Panic Disorder (Goorden et al., 2014; Muntingh et al., 2014). The stepped care intervention included three steps starting with guided self-help, increasing to cognitive behavioral therapy and then to antidepressants. The stepped care intervention was slightly more expensive but also led to greater improvements in quality of life, with an incremental cost-effectiveness ratio of €6965 per QALY, well within common standards for cost per QALY. A small study of 30 adults with Obsessive- Compulsive Disorder found a stepped care model starting with 3 sessions of low intensity counseling plus bibliotherapy using exposure and response therapy materials for the first 6 weeks was equally clinically effective as the standard 17- session therapist-administered Exposure and Response Prevention Therapy but with significantly lower costs to both the patient and health care payers, suggesting likely cost-effectiveness. Non-responders to the low intensity components were followed up with the standard therapist-administered treatment as needed (Tolin et al., 2011).

Clinical and cost-effectiveness trials examining stepped care interventions for other behavioral health disorders also suggest promise for improving cost- effectiveness of care. A randomized trial compared a stepped care intervention to current gold standard treatment for women with bulimia nervosa. The stepped care intervention consisted of guided cognitive behavioral therapy based self- management, adding antidepressants and cognitive behavioral therapy in cases where symptoms continued. Gold standard treatment consisted of cognitive behavioral therapy with addition of fluoxetine if symptoms persisted at high frequency past the fourth week of therapy. Cost per abstinent subject was

437 Delivery Strategies estimated at $12,146 for the stepped care intervention and $20,317 for the current gold-standard treatment after 1 year. The stepped care intervention dominated current gold-standard care with an 81% likelihood of being more effective and less expensive (Crow et al., 2013).

Stepped care models for chronic pain management have also demonstrated clinical benefits when compared to treatment as usual. Bair and colleagues (2015) found that a nurse care manager-delivered stepped care intervention for chronic musculoskeletal pain, consisting of initial protocol-based analgesic management, followed by 12 weeks of cognitive behavioral therapy for treatment resistant patients, reduced pain severity, lowered pain interference and decreased disability compared to treatment as usual. Kroenke and colleagues (2014) compared a stepped care telephone-based collaborative care management intervention for chronic musculoskeletal pain, which used automated assessments and an algorithm-based stepped care medication intervention, to treatment as usual. This stepped care management intervention reduced pain severity, and doubled the likelihood that a patient experienced a clinically significant improvement in pain (i.e. more than 30% reduction in pain severity) by 12 months. Neither trial examined relative costs or cost-effectiveness, but the improved clinical outcomes suggest that stepped care interventions for pain have promise for improving outcomes and cost-effectiveness.

In contrast to the clinical improvements observed with stepped care interventions to treat existing depression, anxiety and chronic pain conditions, stepped care interventions for prevention have had mixed results. An early trial of a stepped care intervention to prevent anxiety or depression in older adults found that the stepped care protocol halved the incidence of mood disorders compared to usual care (van't Veer-Tazelaar et al., 2009). This stepped care protocol consisted of watchful waiting, cognitive behavioral therapy-based bibliotherapy, cognitive behavioral problem solving therapy, and then referral to primary care for medication if necessary. The stepped care intervention cost €4,367 per disorder-free year gained compared to usual care, meaning that cost- effectiveness would depend on willingness to pay (van’t Veer-Tazelaar et al., 2010). Another stepped care program to prevent depression and anxiety in residents of elderly homes found no reduction in the incidence of mood disorders compared to usual care, along with a non-significant increase in costs (€838) with the stepped care intervention (Bosmans et al., 2014). With no clinical benefit nor decrease in cost, the stepped care prevention program was not found to be cost-effective. Similarly, a randomized trial of a stepped care program for secondary prevention of depression in older adults found no clinical benefit over care as usual (Apil et al., 2012). The stepped care program started with watchful waiting, increasing to bibliotherapy, then individual cognitive behavioral therapy, and indicated treatment as needed. The authors suggested that the watchful waiting component might have delayed treatment in some cases, reducing effectiveness of the program.

Stepped care programs for yet other interventions have found them to be lower cost, but also less effective, meaning that cost-effectiveness decisions will depend on willingness to pay. For example, Jakicic and colleagues (2012) compared a

438 Delivery Strategies stepped care intervention versus a standardized counseling protocol for a low- calorie diet and prescribed increase in exercise for weight loss. The program included counseling sessions of fixed intensity and goals in the standard group but customized intensity and strategy in the stepped group. While patients in the standard protocol lost more weight than those in the stepped care program over the next 18 months (8.1% versus 6.9% weight loss), the stepped care program was still effective for producing weight loss and cost significantly less ($785 versus $1,357 per participant).

As these example trials illustrate, stepped care protocols show substantial promise for reducing health care delivery costs while generally maintaining clinical benefits. However, stepped care interventions are not dominant (i.e. cost- saving and more clinically effective) for all disorders, all protocols or all purposes. Stepped care interventions are sometimes less effective or more costly. More research is needed to identify stepped care protocol designs and populations where this approach is beneficial. Implementation strategies to support use of these structured treatment protocols in clinical practice are also needed. Standard clinical practice patterns currently do not support the regular assessment practices needed to inform stepped care treatment decisions. Lastly, stepped care protocols tested to date have examined very specific clinical protocols for specific disorders. It is not clear whether there are elements of stepped care models that could be implemented globally and flexibly to improve cost-effectiveness, or whether cost-effective delivery requires use of specific clinical protocols for each disorder. For example, no trials have examined whether implementation of the general principles of stepped-care have clinical or cost-effectiveness benefits over treatment as usual. Such a trial might compare general mental health implementation of standardized regular assessment of health outcomes over time in combination with clinician training in initial use of low contact interventions across disorders to treatment as usual.

Screening, Brief Intervention and Referral to Treatment (SBIRT) Screening, brief intervention and referral to treatment (SBIRT) is a specific example of a stepped care program that has been well tested and employed as an intervention to address population burden of behavioral health conditions. The SBIRT process uses a three-part, stepped care intervention to target treatment to the members of the population who are most likely to benefit. While all patients are screened to detect problems, a low intensity intervention is only provided to those with signs of risk, and then referral to treatment is only offered to those with substantial risk and enough motivation to engage in treatment. In this way, treatment costs are targeted to those patients with the greatest need for clinical services.

SBIRT is typically used in primary care, community, or emergency and urgent care settings (National Council for Community Behavioral Health care, 2009). As with the mutual help programs that we will discuss later, the majority of clinical trials of this intervention strategy have been conducted to address risky alcohol or other drug use. Generally, a standardized assessment instrument is used to universally screen for behavioral health concerns (e.g., risky alcohol use) among the entire encountered population. If the results of the assessment indicate risky

439 Delivery Strategies behavior, a provider delivers a brief intervention. These brief interventions typically take 2 to 30 minutes, and consist of normative feedback about the health behavior (i.e. how your behavior or risk compares to like members of the population), and motivational interviewing (including, for example, providing a non-judgmental statement of risks and costs of current behavior, offering a menu of assistance options, and giving explicit assurance that the choice of next steps belongs to the patient). If the patient wishes, the provider can then make a referral to a more intensive treatment option.

SBIRT has been shown to reduce risky alcohol use in various populations including primary care patients, college students, and heavy alcohol users admitted to hospitals or in the emergency department.

Computerized versions of SBIRT, where patients complete an assessment on a computer and receive a tailored output similar to that delivered in an in-person session, have also been shown to be effective. Some trials have even found some signs of increased benefit with this approach, including more accurate patient disclosure of risky drinking and better substance use outcomes, with computerized versus in person delivery (Lotfipour et al., 2013; Schwartz et al., 2014; Gryczynski et al., 2015). This suggests that computerized SBIRT programs may be able to increase the cost-effectiveness of this already brief, low-cost intervention.

A clinical trial examined whether a full stepped care-based SBIRT protocol improved clinical and cost-effectiveness outcomes as compared to a minimal alcohol screening and brief intervention protocol in older adults in a primary care practice (Watson et al., 2013). The stepped care intervention consisted of a 20-minute behavior change focused counseling session, followed by motivational enhancement therapy and finally referral to a substance use disorder specialist as needed. The minimal intervention consisted of 5 minutes of advice regarding risks from a health care professional. In both cases, care was triggered based on responses to alcohol screening using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol use and quality of life outcomes, as well as average costs, were not statistically significant between groups. However, 12 months trends favored the stepped care protocol such that the calculated incremental cost effectiveness ratio was £1,100 per QALY gained. This finding suggests that the addition of more intensive stepped care intervention and referral to treatment, at a minimum, does not reduce cost-effectiveness of efforts to reduce risky alcohol use in older adults, and may incur some minimal clinical benefits in a cost- effective manner.

Clinical trials have found mixed results of SBIRT for reducing illicit drug use. More research is needed to determine when and if SBIRT is effective for these substance use problems (Young et al., 2014). While evidence favors universal use of SBIRT for alcohol use in health care settings, SBIRT for illicit drug use problems may be more effective when targeted to persons seeking help for illicit drug use related problems (Saitz, 2014). There have not been clinical trials of SBIRT for other mental or behavioral health conditions to date, although the

440 Delivery Strategies concept has been recommended for treatment of mood disorders, suicidality, and other behavioral health conditions.

Meta-analysis of cost studies of SBIRT for reducing risky alcohol use in primary care settings concluded that studies generally found SBIRT cost-effective or cost- beneficial with little variation due to duration of intervention or the type of provider who delivered it (Angus et al., 2014; Kraemer, 2007). In addition to cost- effectiveness from a health payer perspective, a model of SBIRT for risky drinking found this intervention likely to be cost-effective from a employer perspective, saving an estimated $771 per employee (Quanbeck et al., 2010). Cost-effectiveness models comparing SBIRT for risky alcohol use delivered in outpatient versus emergency department settings found that both were cost- saving and clinically effective, but emergency department delivery resulted in slightly larger effects for lower costs (Barbosa et al., 2015). A cost-effectiveness analysis of screening and brief intervention for risky drinking compared to standard practice in the Netherlands estimated screening and brief intervention cost €5,400 per QALY gained (Tariq et al., 2009). Bischof and colleagues (2008) investigated whether the cost-effectiveness of SBIRT programs could be increased by further utilizing a stepped-care approach for the treatment intervention. Specifically, primary care patients who screened positive for risky drinking were randomized to receive a computerized intervention either followed by three 40-minute telephone-based interventions or followed by the telephone-based interventions as needed based on the effect of the intervention to date. Compared to untreated controls, both protocols produced small to medium effects on drinking outcomes, with no difference in outcomes between the stepped care versus full telephone intervention groups. However, the stepped care group received half of the total minutes of telephone counseling as the full intervention group, suggesting that use of stepped care could lower treatment costs without reducing efficacy.

Initial studies of SBIRT for the detection and treatment of risky drinking demonstrate the potential of this approach for addressing behavioral risks across a population in a cost-effective manner. Further research is needed to determine whether this approach has broader applicability, for example, for addressing mood disorders, risky sexual behavior, suicidality, or insomnia and other sleep disorders.

Coordinated Care Models Other promising strategies for enhancing the cost-effectiveness of behavioral health care delivery focus on improving the organization and coordination of care to both increase the effectiveness of treatment and prevent the need for high-cost emergency or acute inpatient care services. In most health care systems, mental and behavioral health conditions are under-diagnosed and under-treated, leading to late detection and treatment of conditions only after they have become severe and more difficult and expensive to address. Models that encourage earlier intervention on new behavioral health problems and more proactive monitoring and intervention on chronic behavioral health conditions may both improve outcomes, reduce direct and indirect costs related to severe mental

441 Delivery Strategies health conditions, and minimize need for the most costly and intensive emergency mental health services.

The most well developed and tested of such models is the Collaborative Care Model (CCM). In this model, mental and behavioral health services are integrated into primary care medicine to more proactively manage and address emergent and chronic behavioral and mental health concerns in coordination with medical care for physical health conditions. Generally, patients are assigned to a health care “home,” consisting of (1) a primary care physician, (2) care management staff (e.g., a nurse, social worker or psychologist) who coordinate care and can provide brief behavioral treatments and sometimes brief psychotherapy, and (3) consulting specialty mental health providers such as a psychiatrist or clinical psychologist for more complex or treatment-resistant mental health concerns. This model uses a stepped care process, regularly monitoring targeted symptoms and functioning using standardized and validated clinical assessment instruments to determine progress toward goals. When treatment has not been effective or a patient shows signs of relapse, treatment plans are revised and care intensity is increased. This use of structured assessment to guide treatment planning is referred to as “measurement-based care.” In this model, care management staff may monitor patients while they are home, using patient-reported symptoms on standardized assessments to identify when patients need to return for care.

Colocation or integration of services may also improve the efficiency of care delivery, reducing patient no-shows due to, for example, logistical barriers to accessing services or patient reluctance to attend treatment in a designated mental health setting as a result of mental health stigma. Colocation or integration may also streamline patient scheduling and billing. This improved efficiency can reduce costs from lost clinician time and indirect hospital costs.

Additionally, use of a collaborative care team may reduce treatment costs by encouraging delivery of less specialized treatment components by less expensive provider types. For example, psychiatrists and psychologists may provide consultation and treatment planning and might deliver more complicated psychotherapies, but less costly staff, such as social workers or nurses, may provide on-going case management, assessment, monitoring, and supportive treatments. This team-based approach allows all providers on the team to “work at the top of their license,” minimizing instances of high-cost providers delivering treatment elements that could be done by another less expensive team member. Collaborative care may also reduce redundant procedures, such as repeated assessments by primary care and specialist providers.

As summarized in the chapter on Depressive Disorders, studies of Collaborative Care Management (CCM) in primary care, including stepped care versions, found CCM consistently cost-effective for the treatment of depressive disorders. CCM was found to be effective for depression across a broad array of populations in repeated trials, with effects persisting for at least two years. Likewise, as summarized in the chapter on Anxiety Disorders, multiple trials comparing CCM to usual care found CCM to be cost-effective for treatment of

442 Delivery Strategies multiple anxiety disorders, including panic disorder. Given the relatively strong evidence for cost-effectiveness of CCM for depressive and anxiety disorders, trials examining whether this model of care delivery is clinically and cost- effective for general mental health service delivery more broadly (e.g., including maintenance treatment for substance use disorders and serious mental illness) seem warranted. Additional studies of CCM will improve and broaden application of this model to relevant populations. But, given cost-effectiveness of this model in trials to date, efforts to encourage implementation of this program in health care systems are likely to, at the minimum, improve mood disorders and quality of life outcomes in a cost-effective manner.

PROMISING AREAS AND STRATEGIES FOR IMPROVING COST- EFFICIENCY OF HEALTH CARE DELIVERY

Measurement-Based Care and At-Home Health Monitoring Measurement-based care is implicitly included in most stepped care interventions, but has not been isolated as an intervention component in cost- effectiveness trials. Measurement-based care refers to the practice of conducting standardized assessments at pre-planned times during the course of care and then using the results of the assessments to guide decisions about subsequent treatment. For example, in stepped care models, the findings of assessments are often used to determine whether patients need to receive a different intervention or level of care. Measurement-based care may apply these assessments for decision-making during standard in-person treatment visits; alternatively, assessments may be conducted during the period between treatment visits, either via clinician-based assessment (e.g., nurse care manager or health technician phone follow-up) or using automated monitoring technology (e.g., mobile or web-based self-assessment, or remote monitoring devices to assess activity or sleep). Assessment between treatment visits has the potential to reduce treatment costs by eliminating or delaying treatment visits when they are not needed, and improve clinical efficacy by speeding clinical response when needed to address problems with or inadequacies of current treatment plans (e.g. side effects or logistical barrier to treatment participation). A centralized telehealth care management program for pain and depression in patients with cancer used automated monitoring of symptoms and increased depression-free days and QALYs relative to usual care at an incremental cost between $18,018 and $36,035 per QALY. While substantial additional research is needed to evaluate the clinical and cost-effectiveness of various methods and uses of measurement- based care, this initial trial demonstrated that telehealth programs using automated measurement systems can improve outcomes within standard willingness to pay thresholds for some conditions. This strategy shows promise for improving clinical and cost outcomes. Ongoing technological advances in automated and out-of-clinic assessment systems, and increasing use of models of care delivery that rely on assessment-based treatment planning, make this strategy ripe for innovation and investigation.

Addressing Common Contributing Factors to Comorbid Health Conditions Most treatments have been designed and tested for a specific diagnosed clinical condition, but common cognitive or behavioral tendencies or habits may

443 Delivery Strategies underlie multiple diagnosed clinical conditions. For example, anxiety-related avoidance may encourage substance use, prevent engagement in activities and exercise, and reduce medication adherence, contributing to substance use disorders, metabolic syndrome, obesity, and unmanaged medical conditions. In this example, addressing anxiety-related avoidance may encourage behavior change that improves outcomes across these disorders.

Shared cognitive or behavioral risk factors have been identified for a wide variety of disorders. Similar cognitive and behavioral therapies have been shown to be effective for treatment of a variety of conditions, including anxiety, depression, chronic pain, eating disorders, and substance use disorders. Currently, however, patients with multiple conditions are treated separately for each condition, typically with a set of 8 to 12 sessions tailored for each diagnosis. It might be more efficient to identify core underlying cognitive and behavioral vulnerabilities for each patient and then tailor treatment and skills building to address the areas that are most difficult for the patient.

Efforts to treat behavioral health conditions by addressing contributing factors rather than the diagnosis as a whole are in their infancy. The National Institute for Mental Health (NIMH) has included a strategic focus on identifying core processes or neural circuits that underlie clinically meaningful problems, referred to as their “Research Domain Criteria Project.” These efforts will help to identify and differentiate core underlying pathology so targeted treatments can be developed and tested. Already, some efforts to consolidate treatment protocols have had some success. For example, a common protocol for treatment of depression and anxiety problems across disorders has been developed and was found to be effective in several small clinical trials (e.g. Bullis et al., 2014; Farchione et al., 2012). Protocol development and trials are still in an early stage. Initial small trials are encouraging, suggesting that the approach may be similarly clinically effective to diagnosis-specific protocols, and may be effectively delivered in group and Internet-based protocols (e.g., Norton and Barrera, 2012; Ebert et al., 2013; Bullis et al., 2014; Ejeby et al., 2014). Once clinically effective protocols are fully developed, cost-effectiveness studies can test whether treating behavioral pathology across conditions improves the efficiency and effectiveness of behavioral health care delivery.

Addressing Community, Social, and Economic Barriers to Health Health care has historically focused on prescribing effective treatments to patients and expecting them to adhere to or implement them. There is growing recognition that community, social and economic barriers contribute to poor health care outcomes and prevent treatment adherence. Expanding health care models to address these barriers may be cost-effective, particularly from a societal payer perspective. Examples of interventions that target both community, social and economic challenges and health outcomes include housing first models, vocational rehabilitation programs, transportation and health care at home programs, and harm reduction programs (e.g., needle exchange, opioid overdose education and naloxone distribution). Additionally, public health and policy interventions may both address these barriers and

444 Delivery Strategies promote health including community efforts to develop safe parks and biking and walking routes, policing efforts and marketing restrictions to discourage risky behaviors (e.g., underage drinking and smoking, driving under the influence), community efforts to improve low-income housing options and access to healthful food and activities, health education, and expanding health insurance coverage for preventative care and health behavior interventions.

These interventions have rarely been tested in randomized cost-effectiveness trials. However, some studies that address or model cost outcomes exist.

Studies of supported employment programs, where persons with mental health or other disabilities are assisted with obtaining and maintaining employment, suggest that while these programs may not be cost-efficient (i.e. generate more benefits than costs) over the first several years, they become cost-efficient from a taxpayer perspective over longer time periods (e.g., greater than four years) with benefits increasing over time (Cimera, 2000).

Ensuring housing and improving stability or quality of housing for patients with chronic mental health or substance use problems is a target of a number of public and non-profit programs. These programs generally seek to provide housing, and ideally independent housing, for persons with behavioral health problems and housing instability or homelessness. They may involve providing housing vouchers, or connecting patients with affordable, often subsidized, housing options. The “Housing First” approach emphasizes the importance of addressing housing instability early in treatment of mental health disorders, as a way of improving the likelihood and stability of recovery. This is in contrast to some prior approaches that provided housing assistance only after recovery was achieved. Generally, the unsubstantiated rationale for providing housing only after recovery was that housing would act as an incentive for clinical improvement. But, as housing instability can contribute to stress and logistical challenges with engaging in treatment, obtaining employment, and other recovery-oriented activities, providing housing as a component of treatment may enhance clinical improvement as well as improve quality of life.

While randomized cost-effectiveness trials of these approaches are lacking, existing observational program evaluation data suggests that this may be a reasonably low-cost approach that may improve mental health outcomes, with potential for reduction in hospitalization and criminal justice related costs. For example, an evaluation of a Full-Service Partnership program that used the Housing First model plus Assertive Community Treatment as needed from a team of mental health professionals found the following impact on costs for patients with chronic, serious mental illness from the perspective of the county: Outpatient and housing costs increased, while inpatient, emergency department and jail costs decreased. The Full-Service Partnership significantly improved patients’ quality of life, and 82% of the cost of the program was offset by medical and justice system cost-savings (Gilmer et al., 2010). An evaluation of another pilot program for patients with chronic serious mental illness found that among patients receiving independent housing support, higher quality housing in better neighborhoods was associated with lower mental health care costs (Harkness et

445 Delivery Strategies al., 2004). Additional trials are needed to optimize housing programs for patients with housing instability and mental illness and determine cost- effectiveness. Evaluations suggest that considering and addressing problems with housing that may contribute to poor functioning and low quality of life among those with mental illness is a promising avenue for cost-effective program improvement.

Another under-explored contributor to health care costs is household food insecurity. A recent study in Canada found that compared to households with no problems with food security, total health care costs were higher by 16% in households with marginal food insecurity, 32% in households with moderate food insecurity, and 76% in households with severe food insecurity (Tarasuk et al., 2015). Such findings suggest that development of programs that address challenges with stable and proper nutrition might be cost neutral, if they successfully offset increased health care costs.

Challenges with transportation and mobility can make it difficult for patients to access services provided at a medical center or clinic. These challenges may be particularly problematic for persons in rural areas or with conditions that affect ability to drive. Patients who cannot access regular ambulatory services may develop serious acute health care issues that require emergency services or hospitalization. Failing to address transportation challenges in health care delivery models can lead to both unnecessary health care costs and poor health outcomes. Programs that do address these transportation barriers are under active development and study, particularly for patients with multiple chronic conditions, patients who have been recently or repeatedly hospitalized, patients being discharged from the hospital with substantive rehabilitation or chronic care needs, and older adults with developing dementia (e.g. Matthew-Maich et al., 2016; Low and Fletcher, 2015). These programs are testing in-home consultation or care, often with nurses or social workers, and telehealth from home that allows visits with a provider without leaving the house. An added benefit of these programs is that they allow providers to educate and work with patients on disease management challenges in the setting in which the patients will need to carry out health behaviors. This may allow them to concretely model and observe the patient in conducting health behaviors, to suggest solutions to barriers that might prevent the patient from regular practice of health behaviors, and address problems before they progress.

In-home care programs have shown substantial promise for reducing hospital admissions and emergency care while improving health outcomes and quality of life for patients with serious chronic disease (Health Quality Ontario, 2013). For example, a non-randomized evaluation of a home-health care program for patients with multiple chronic conditions in Barcelona found reduced admissions, emergency visits and costs per person per day after entry into the program, allowing their hospital to reduce acute care beds by 1 for every 50 patients added to the program (Vila et al., 2015). Such studies demonstrate that home health care programming can be beneficial and have the potential to be cost-effective or even cost-saving when delivered to high-risk, high-cost patient populations. Pilot programs and studies have used this model with a wide variety of other

446 Delivery Strategies populations to address various disorders or risks, from post-discharge transitional rehabilitation programs to dental caries prevention (e.g., Low et al., 2015; Koh et al., 2015) with mixed evidence for clinical and cost-effectiveness even within target populations (e.g., Tappenden et al., 2012; Brettschneider et al., 2015). Further research and randomized trials are needed to delineate populations for which home health care is cost-effective and to define the optimal intensity and content of home health care services for specific populations. While research into this modality of care is still in its infancy, this strategy holds promise for cost-effective service delivery for at least some patient populations.

Lastly, implementation of harm reduction programs may reduce negative health outcomes and mortality in a cost-effective manner. Harm reduction programs are generally designed to prevent adverse outcomes of mental health conditions without directly addressing the underlying mental health condition. For example, overdose education and naloxone distribution programs have been used to reduce mortality and morbidity related to opioid overdose, primarily in populations of persons with opioid use disorders (e.g., heroin or prescription opioid misuse). These programs teach high-risk opioid users and those in their social network to identify the signs of an opioid overdose and administer the drug naloxone, which blocks the effect of the opioid, preventing death or morbidity related to lack of oxygen from opioid-related respiratory depression. Cost-effectiveness models suggest that naloxone distribution programs are well within standard willingness to pay thresholds for cost-effectiveness, with ICERs estimated at $438 per QALY, with a worst-case scenario model estimate of $14,000 per QALY (Coffin & Sullivan, 2013).

Likewise, needle exchange programs provide clean needles to persons with substance use disorders who use drugs intravenously. These programs have been shown to reduce the spread of infectious disease, such as HIV and Hepatitis C. An evaluation of needle exchange programs in Australia between 2000 and 2010 suggest that these programs were very cost-effective at Aust$416 to Aust$8750 per QALY gained; health care cost models suggest that the programs would eventually be cost-saving with current reductions in health care costs and more expected in the future (Kwon et al., 2012). Cost models suggest that expansion of needle exchange programs in the United States would be cost- saving due to reduction in HIV infections (Nguyen et al., 2014).

Incorporating harm reduction models into mainstream health care delivery models is a promising area for enhancing cost-effective care; these services have typically been implemented only within public health programs, but may be effective methods for reducing adverse events, improving quality of life, and reducing health care costs for high-risk patient populations.

APPROACHES TO MINIMIZE CLINICAL PROVIDER CONTACT The majority of costs for treatment of behavior-related health conditions are salary costs for the health professionals delivering the intervention. Effective methods of delivering behavioral health interventions that minimize health professional contact are promising for increasing cost-effectiveness of these

447 Delivery Strategies treatments. A variety of promising methods for reducing the amount of health professional involvement while still improving health outcomes have been developed and are being tested. First, computerized therapy tools have been developed to allow persons to learn and practice cognitive and behavioral skills, connect with community resources, and communicate with supportive networks either independently or with minimized intervention by a health care provider. Most commonly, these consist of cognitive behavioral therapy protocols adapted from effective provider-led individual or group therapy interventions to be accessed via the Internet for use in self-management. Second, mutual help and peer support interventions and organizations have developed in the community and typically offer support for health behaviors at no cost for participation. Health care systems are exploring and testing methods to more effectively encourage participation in these mutual help and peer support organizations to maximize benefits from these non-professionally led groups and reduce reliance on the health care system. Third, as discussed earlier, health care organizations are testing stepped care interventions, where low intensity treatments are used as first-line care with close monitoring and increasing intensity of services for patients who do not respond. This strategy makes use of low cost interventions that are effective for a subpopulation of patients, reserving higher cost treatments for persons who do not recover with lower cost care options.

Telehealth The advent of new technologies and innovative use of existing ones are leading to rapid expansion in clinical applications. Telehealth—providing health-related information and services at a distance via information technologies such as the Internet or phone—allows the provision of services with either less provider contact or into communities that do not otherwise have access to resources like trained specialists. Telehealth can also benefit a variety of populations that might not be immediately evident, such as patients with depression who have difficulty leaving their home, patients with a chronic condition like cancer that leaves them feeling weak or immobile without assistance, or even caregivers of patients with dementia who have limited free time. However, in addition to addressing issues of access and reach, telehealth must also achieve meaningful changes in health outcomes.

There are a few broad categories of telehealth interventions. Some are essentially the same as in-person treatments but utilize real-time videoconferencing or telephone services to administer treatment at a distance. While these do address issues of access and reach, the do not address costs to the health care system and are not the focus of this review. Others incorporate trained health professionals in a more limited capacity (e.g., email access), while still others are completely self-driven (e.g., interactive website). Once these latter types of interventions are developed, they can be made available (even for free) and incur minimal maintenance costs. In some cases, telehealth is offered in addition to in-person care, but in many cases, it is offered in lieu of it. Regardless, the lower costs of implementation compared to in-person interventions indicate the strong potential for cost-effectiveness if clinical effectiveness can be maintained.

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While individual telehealth interventions have indicated both clinical- and cost- effectiveness, meta-analyses have surmised there are not compelling data to date to conclude that telehealth is more clinically effective (Ekeland et al., 2010) or cost-effective (Whitten et al., 2002; Mistry, 2012) than in-person interventions. Notably, a meta-analysis for older adults found mostly positive effects, particularly for behavioral outcomes such as treatment adherence, self-efficacy, and quality of life as well as for costs (van den Berg et al., 2012). Importantly, these reviews include telemedicine strategies like screening, diagnosis, monitoring, or general patient care; below we focus on behavioral and psychosocial telehealth.

A review of Internet-based interventions for psychosocial health in chronic neuropsychiatric and medical conditions—most commonly self-guided Cognitive Behavioral Therapy—found significant psychosocial benefit from the web-based interventions in over half the studies, with greater effects for patients with mood disorders. Positive effects were found in almost 70% of the studies targeting anxiety or depression, with more limited or mixed results in trials for improving psychosocial health of patients with other chronic conditions (e.g., diabetes, cancer). The researchers concluded web-based interventions may be efficacious but not consistently across disorders, noting that interventions for mood disorders target psychosocial outcomes more closely linked to symptoms and tend to be more structured while interventions for diabetes and cancer do not target symptoms directly and tend to be more self-directed (Paul et al., 2013).

A review specific to Internet-based Cognitive Behavioral Therapy (CBT)—often including asynchronous text-based therapist contact—found applications across 25 clinical disorders, with the most studies for depression, anxiety disorders, and chronic pain, but only strong evidence as a well-established treatment for depression, social phobia, and panic disorder. Large effect sizes were also found for generalized anxiety disorder, obsessive–compulsive disorder, posttraumatic stress disorder, severe health anxiety, irritable bowel syndrome, eating disorders, and cannabis use. In general, Internet-based CBT produced equivalent effects to conventional CBT, with effectiveness varying by disorder in relation to effectiveness differences seen with in-person treatment (i.e. for disorders where conventional CBT is effective, Internet-based CBT is effective). Limited cost- effectiveness data indicated Internet-based CBT had more than 50% likelihood of being more cost-effective than conventional CBT or no treatment if the willingness to pay threshold were zero (Hedman et al., 2012).

For chronic medical conditions, one example is diabetes. Telehealth already provides a mechanism for improved monitoring and real-time adjustment for glucose levels and insulin administration. Given the importance of lifestyle modifications for type 2 diabetes, a review specific to Internet-based lifestyle modifications suggested possible efficacy, with four of the nine studies demonstrating significant improvements (two in diet and/or physical activity and two in glycemic control). No studies improved medicine adherence. The researchers noted some commonalities in the successful interventions, including interactivity, personalized feedback, and opportunities for peer support (Cotter et al., 2014).

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In general, the inclusion of human support in Internet-based interventions (e.g., phone/email from coach/therapist) seems to lead to greater adherence and better outcomes, although this may still vary between disorders. One hypothesis for this is the accountability provided with adherence goals, monitoring, scheduled contact, review of progress, and feedback. These insights could also inform other strategies for enhancing adherence (Mohr et al., 2013).

The nascent field of telehealth is already too vast for us to review comprehensively here. However, it is clear that the exploration of telehealth interventions as cost-effective solutions will continue to grow in the future. Even when cost data are not available, demonstrated clinical efficacy of self- management telehealth interventions may imply cost-effectiveness given the typically lower costs of implementation for telehealth. Together, telehealth interventions that provide automated behavioral interventions show promise for demonstrating cost-effectiveness, with robust clinical effectiveness for many disorders and relatively low cost delivery.

Mutual Help and Other Peer Support Interventions Mutual help groups involve peers providing support for behavior change and recovery, typically outside of a formal health care setting. This model of behavioral health service is exemplified by the 12-step mutual help model developed for the treatment of alcohol use disorders and used in Alcoholics Anonymous meetings. Mutual help groups are organized and lead by persons that share a health challenge. They are typically open to anyone and do not charge for participation. They provide psychosocial support, models for recovery, problem-solving assistance, and connection with community resources and learned experience. The success of this mutual help model has lead to the expansion of both the 12-step model for use with other chronic conditions and to the development of other mutual help organizations that use similar formats but with different focus, structure, or philosophy.

Persons who engage in mutual help groups have been shown to have better clinical outcomes. This has been studied most extensively for mutual help group participation among patients with substance use disorders.

Humphreys and Moos (1996) prospectively studied help-seeking problem drinkers who chose to initially enter Alcoholics Anonymous versus professional treatment services. Although the group choosing to receive care via Alcoholic Anonymous reported more consequences of drinking and lower income and education at baseline, outcomes were statistically indistinguishable after three years. Alcohol use and consequences and mental health outcomes were improved in both groups. To achieve similar clinical outcomes, patients initially attending Alcoholics Anonymous incurred significantly lower health care costs over the three-year period, with total costs of $2,251 for those starting care in mutual help versus $4,077 for those starting care in professional treatment.

In a second naturalistic study, Humphreys and Moos (2001) examined mental health treatment costs in the year after discharge from inpatient substance use

450 Delivery Strategies disorder programs. Half of the programs used a 12-step focused philosophy and encouraged mutual help group participation, and half used cognitive behavioral therapy-focused treatment. At one year, patients discharged from 12-step focused programs were more likely to be abstinent from alcohol use (45.7% versus 36.2%); there were no differences between groups in terms of substance- related problems, mental health symptoms or distress. Patients discharged from 12-step focused programs were significantly more engaged in mutual help groups over the next year, and used significantly less professional treatment. Total mental health care costs were significantly lower for patients discharged from 12-step programs ($7,400) versus cognitive behavioral programs ($12,129). A follow-up study found that this cost difference continued into future years, with patients treated in the cognitive behavioral focused inpatient programs continuing to use more professional services with greater associated costs, and patients treated in the 12-step focused program having greater abstinence rates (Humphreys & Moos, 2007).

Given the clinical effectiveness and potential cost-savings of mutual help, clinical interventions to encourage patient participation in mutual help groups have been developed and tested. Timko and colleagues (2011) tested the effectiveness of an intensive referral protocol to encourage participation in mutual help by patients with mental health and substance use disorders. In this protocol, patients were provided four group sessions. These sessions included sharing information, an introduction to mutual help groups, and connection to volunteers from local mutual help groups who were willing to facilitate the patient’s participation in a group. Patients randomized to intensive referral had significantly better substance use and mental health outcomes at six months. For example, those with intensive referral averaged only 0.7 days of substance use in the last month, compared with 2.4 days among those with standard referral. These benefits were obtained even with relatively low participation in mutual help groups among those intensively referred. With only 23% in the intensive referral condition attending a group, it is possible that outcomes might be improved with an intervention that more effectively encouraged participation. Based on clinical trials and treatment practice to date, the following practices are recommended for use in health care settings to encourage patient engagement in mutual help groups: (1) recommend and provide information about the availability and benefits of mutual help groups. Here, it is helpful for clinicians to maintain a list of local mutual help group meetings, including location and times. It is also recommended that clinicians attend an open meeting, so that they can answer questions and address patient anxiety about the experience; (2) discuss patient reactions to meetings and help address barriers to attendance; and (3) connect patients with current mutual help group members. Here, clinicians should form a list of their current and former patients who would be willing to help introduce new patients to mutual help groups.

Clinical data on effectiveness of mutual help groups is less available, but still promising for patients with other mental health problems. A review of effectiveness studies found 12 studies examining outcomes of mutual help groups for chronic mental illness, mood disorders or bereavement (Pistrang et al, 2008). Seven studies showed positive outcomes for those attending, five of these

451 Delivery Strategies studies found with no difference between those attending mutual help and those not attending, and no studies showed negative effects. Of the seven positive studies, two were randomized controlled trials that found that mutual help groups had equivalent outcomes to more expensive professional treatment. While additional controlled trials are needed to firmly establish both clinical and cost-effectiveness of mutual help as a treatment modality for mental health conditions, the model has demonstrated feasibility, no adverse effects, and strong promise for improving cost-effectiveness of care.

KEY POINTS • New health care delivery models show promise for improving the cost- effectiveness of behavioral health interventions.

• Modifications to make care delivery more efficient have demonstrated cost- effectiveness in some trials for some conditions. This includes stepped care models, Screening, Brief Intervention and Referral to Treatment (SBIRT) models, and Collaborative Care Models.

• Novel approaches, such as harm reduction programs, interventions to address community, social or economic barriers to health as part of health care, and psychotherapeutic treatments that target common transdiagnostic symptoms or problems, have demonstrated feasibility and findings suggest cost-effectiveness for some models and conditions.

• Modifications to reduce the amount of contact with a health care provider also have demonstrated promising findings that suggest cost-effectiveness. This includes computerized psychosocial treatments such as Internet-based cognitive behavioral therapy and mutual help groups.

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To our knowledge, this text is the first of its kind to provide a systematic and detailed review of the cost-effectiveness of behavioral health interventions.

This essential resource is designed for health care professionals and health decision-makers that are responsible for documenting, implementing, and improving behavioral treatments in the following settings:

* School * Private Practice * Primary Care * Private Insurance Plans * Workplace * Group Practice * Chronic Care * Public Insurance Plans

Preface: Understanding Cost-Effectiveness Research

Part 1: Neuropsychiatric Disorders This section documents cost-effective behavioral interventions for chronic neuropsychiatric disorders in youth and adults in the following domains: • Anxiety Disorders • Eating Disorders • Depressive Disorders • Alcohol Use • Bipolar Disorders • Tobacco Use • Schizophrenia • Illicit Drug Use • Personality Disorders • Disruptive Behavior in Youth • Deliberate Self-Harm

Part 2: Behavioral Medicine This section provides current findings on cost-effective behavioral strategies and lifestyle interventions to manage medical conditions including: • Healthy Weight • Chronic Pain • Metabolic Syndrome • Dementia • Sleep Disorders • End-of-Life Care • Chronic Somatic Symptoms • Other Medical Disorders

Epilogue: Promising Healthcare Strategies To Improve Cost-Effectiveness This chapter reviews potential cost-effective solutions to improve healthcare delivery that have been found to work for many populations.

Overall, this text will help you to identify, implement, and optimize cost-effective and health-enhancing behavioral interventions.

ISBN 9780983246541

9 780983 246541