Prescription Drugs Information Bulletin

EMCDDA DOCUMENTATION CENTRE INFORMATION BULLETIN

PRESCRIPTION DRUGS INFORMATION BULLETIN

12 September 2016

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Saving lives - innovative solutions to the opioid crisis A national symposium on law enforcement and public health partnerships Minneapolis, MN September 7-8, 2016 http://www.hazelden.org/web/public/event.view?eventId=5638413

GREY LITERATURE

Prescription drug use and misuse in the United States: results from the 2015 National Survey on Drug Use and Health Hughes, A; Williams, M R; Lipari, R N; and Bose, J; Copello, E A P; Kroutil, L A Substance Abuse and Mental Health Services Administration (SAMHSA) Rockville, MD: September 2016

Background Misuse of prescription psychotherapeutic drugs is second only to marijuana as the nation’s most prevalent illicit drug use issue. In 2015, the National Survey on Drug Use and Health (NSDUH) questionnaire was redesigned regarding the data collection regarding four categories of prescription psychotherapeutic drugs: pain relievers, tranquilizers, stimulants, and sedatives. For the first time, NSDUH respondents were asked to report about any past year use of prescription drugs, which includes the use of one’s own prescription medication as directed by a doctor, as well as misuse. In addition, misuse was redefined in 2015 as use in any way not directed by a doctor, including use without a prescription of one’s own; use in greater amounts, more often, or longer than told to take a drug; or use in any other way not directed by a doctor. Methods This report presents 2015 NSDUH findings for people aged 12 or older regarding the past year use or misuse of prescription psychotherapeutic drugs and related topics. Estimates for selected outcomes are presented by age, gender, race, Hispanic origin, and county type. Statistically significant differences are noted within selected subgroups. Results In 2015, an estimated 119.0 million Americans aged 12 or older used prescription psychotherapeutic drugs in the past year, representing 44.5 percent of the population. About 97.5 million people used pain relievers (36.4 percent), 39.3 million used tranquilizers (14.7 percent), 17.2 million used stimulants (6.4 percent), and 18.6 million used sedatives (6.9 percent). In 2015, 18.9 million people aged 12 or older (7.1 percent) misused prescription psychotherapeutic drugs in the past year. This number included 12.5 million people who misused pain relievers in the past year (4.7 percent), 6.1 million who misused tranquilizers (2.3 percent), 5.3 million who misused stimulants (2.0 percent), and 1.5 million who misused sedatives (0.6 percent). However, most people (84.1 percent) who used prescription drugs in the past year did not misuse them. Past year users of other substances were more likely than people aged 12 or older to have misused prescription drugs. For example, 72.1 percent of past year heroin users and 5.9 percent of past year alcohol users misused pain relievers in the past year. Adults aged 18 or older who did not have mental illness in the past year were less likely than adults with mental illness to have misused prescription drugs in the past year. In 2015, 2.1 million people aged 12 or older were recent initiates for pain reliever misuse (i.e., misused for the first time in the past year), 1.4 million were recent initiates for tranquilizer misuse, 1.3 million were recent initiates for stimulant misuse, and 425,000 were recent initiates for sedative misuse. On average, recent initiates aged 12 to 49 initiated the misuse of prescription drugs in their early to late 20s. About 1.0 percent of people aged 12 or older (2.7 million) had a prescription drug use disorder in the past year, including 2.0 million people with a pain reliever use disorder, 688,000 with a tranquilizer use disorder, 426,000 with a stimulant use disorder, and 154,000 with a sedative use disorder. In 2015, as part of their most recent substance use treatment, 822,000 people received treatment for the misuse of pain relievers, 293,000 people received treatment for tranquilizer misuse, 139,000 received treatment for stimulant misuse, and 116,000 received treatment for sedative misuse. Among people aged 12 or older who misused prescription pain relievers in the past year, the most commonly reported reason for their last misuse was to relieve physical pain (62.6 percent). Among past year misusers of tranquilizers, the most commonly reported reasons were to relax or relieve tension (44.9 percent) or to help with sleep (20.4 percent). Commonly reported reasons for misuse among stimulant misusers were to help be alert or stay awake, help concentrate, or help study (26.8, 26.5, and 22.5 percent, respectively). Among past year sedative misusers, the most common reason was to help with sleep (71.7 percent). Even if people misused prescription drugs for conditions for which these drugs are typically prescribed (e.g., for pain relief or to help with sleep), use without one’s own prescription or use more often or at a higher dosage than prescribed nevertheless constitutes misuse. Among people aged 12 or older who misused pain relievers in the past year, the most common source for the last pain reliever that was misused was from a friend or relative (53.7 percent), and about one third misused a prescription from one doctor. About 1 in 20 people who misused pain relievers bought the last pain reliever they misused from a drug dealer or stranger. Conclusions Compared with prior NSDUH data collection efforts, collecting more detailed information on the use and misuse of a comprehensive set of prescription drugs was determined to be more useful for policy and research purposes. The 2015 estimates provide a more nuanced understanding of prescription drug misuse in the United States. http://klmsvr.emcdda.org/vlib/Prescription_drug_use_and_misuse_in_the_Unit ed_States- results_from_the_2015_National_Survey_on_Drug_Use_and_Health.pdf

Key substance use and mental health indicators in the United States: results from the 2015 National Survey on Drug Use and Health Bose, J; Hedden, S L; Lipari, R N; Park-Lee, E Substance Abuse and Mental Health Services Administration (SAMHSA) Rockville, MD: September 2016

This national report summarizes key findings from the 2015 National Survey on Drug Use and Health (NSDUH) for indicators of substance use and mental health among people aged 12 years old or older in the civilian, non- institutionalized population of the United States. Includes illicit and prescription drug use. http://klmsvr.emcdda.org/vlib/Key_substance_use_and_mental_health_indicat ors_in_the_United_States- results_from_the_2015_National_Survey_on_Drug_Use_and_Health.pdf

SAMHSA Prescription Drug Abuse Weekly Update Issue 190 September 8, 2016 http://www.dsgonline.com/PAW/2016/2016_09_08/paw_2016_09_08.html

JOURNAL ARTICLES

Treatment / Prevention

A new abuse-deterrent opioid—Xtampza ER Katz, M H Journal of the American Medical Association 316, 9, p.986-987, 2016

Performance of the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool for substance use screening in primary care patients McNeely J, Wu LT, Subramaniam G, Sharma G, Cathers LA, Svikis D, Sleiter L, Russell L, Nordeck C, Sharma A, O'Grady KE, Bouk LB, Cushing C, King J, Wahle A, Schwartz RP Annals of Internal Medicine 6 September 2016 doi: 10.7326/M16-0317 [Epub ahead of print]

Background: Substance use, a leading cause of illness and death, is underidentified in medical practice. Objective: The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was developed to address the need for a brief screening and assessment instrument that includes all commonly used substances and fits into clinical workflows. The goal of this study was to assess the performance of the TAPS tool in primary care patients. Design: Multisite study, conducted within the National Drug Abuse Treatment Clinical Trials Network, comparing the TAPS tool with a reference standard measure. (ClinicalTrials.gov: NCT02110693). Setting: 5 adult primary care clinics. Participants: 2000 adult patients consecutively recruited from clinic waiting areas. Measurements: Interviewer- and self-administered versions of the TAPS tool were compared with a reference standard, the modified World Mental Health Composite International Diagnostic Interview (CIDI), which measures problem use and substance use disorder (SUD). Results: Interviewer- and self-administered versions of the TAPS tool had similar diagnostic characteristics. For identifying problem use (at a cutoff of 1+), the TAPS tool had a sensitivity of 0.93 (95% CI, 0.90 to 0.95) and specificity of 0.87 (CI, 0.85 to 0.89) for tobacco and a sensitivity of 0.74 (CI, 0.70 to 0.78) and specificity of 0.79 (CI, 0.76 to 0.81) for alcohol. For problem use of illicit and prescription drugs, sensitivity ranged from 0.82 (CI, 0.76 to 0.87) for marijuana to 0.63 (CI, 0.47 to 0.78) for sedatives; specificity was 0.93 or higher. For identifying any SUD (at a cutoff of 2+), sensitivity was lower. Limitations: The low prevalence of some drug classes led to poor precision in some estimates. Research assistants were not blinded to participants' TAPS tool responses when they administered the CIDI. Conclusion: In a diverse population of adult primary care patients, the TAPS tool detected clinically relevant problem substance use. Although it also may detect tobacco, alcohol, and marijuana use disorders, further refinement is needed before it can be recommended broadly for SUD screening. Public Health / Policy / Legislation / Law Enforcement

Evaluation of US Federal legislation for opioid abuse: 1973-2016 Ruble, J H Journal of Pain & Palliative Care Pharmacotherapy 1 September 2016 [Epub ahead of print]

The 114th Congress (2014-2016) has received recent attention for the high number of legislative bills directed to the public health crisis in prescription opioid abuse. The US government does not have a single source for determining public policy; however, the people expect that there will be some level of efficiency and coordination between federal and state leaders to improve the nation's health. A search of the National Library of Congress database to analyze legislative bills introduced between 1973 and 2016 and which contain the term "opioid" identified 127 bills that characterize consistency and coordination with other governmental efforts in prescription opioid abuse. Despite the recent number of introduced bills, there does not appear to be a close coordination between Congress and Federal Administrative agencies regarding this crisis.

Opioid use disorder in pregnancy: health policy and practice in the midst of an epidemic Krans EE, Patrick SW Obstetrics & Gynecology 128 ,1, p.4-10, 2016

Opioid abuse among pregnant women has reached epidemic proportions and has influenced maternal and child health policy at the federal, state, and local levels. As a result, we review the current state of opioid use in pregnancy and evaluate recent legislative and health policy initiatives designed to combat opioid addiction in pregnancy. We emphasize the importance of safe and responsible opioid-prescribing practices, expanding the availability and accessibility of medication-assisted treatment and standardizing care for neonates at risk of neonatal abstinence syndrome. Efforts to penalize pregnant women and negative consequences for disclosing substance use to health care providers are harmful and may prevent women from seeking prenatal care and other beneficial health care services during pregnancy. Instead, health care providers should advocate for health policy informed by scientific research and evidence-based practice to reduce the burden of prenatal opioid abuse and optimize outcomes for mothers and their neonates.

Drugs as instruments: describing and testing a behavioral approach to the study of neuroenhancement Brand R, Wolff W, Ziegler M Frontiers in Psychology 7, 1226-1237, 2016 Neuroenhancement (NE) is the non-medical use of psychoactive substances to produce a subjective enhancement in psychological functioning and experience. So far empirical investigations of individuals' motivation for NE however have been hampered by the lack of theoretical foundation. This study aimed to apply drug instrumentalization theory to user motivation for NE. We argue that NE should be defined and analyzed from a behavioral perspective rather than in terms of the characteristics of substances used for NE. In the empirical study we explored user behavior by analyzing relationships between drug options (use over-the-counter products, prescription drugs, illicit drugs) and postulated drug instrumentalization goals (e.g., improved cognitive performance, counteracting fatigue, improved social interaction). Questionnaire data from 1438 university students were subjected to exploratory and confirmatory factor analysis to address the question of whether analysis of drug instrumentalization should be based on the assumption that users are aiming to achieve a certain goal and choose their drug accordingly or whether NE behavior is more strongly rooted in a decision to try or use a certain drug option. We used factor mixture modeling to explore whether users could be separated into qualitatively different groups defined by a shared "goal × drug option" configuration. Our results indicate, first, that individuals' decisions about NE are eventually based on personal attitude to drug options (e.g., willingness to use an over-the-counter product but not to abuse prescription drugs) rather than motivated by desire to achieve a specific goal (e.g., fighting tiredness) for which different drug options might be tried. Second, data analyses suggested two qualitatively different classes of users. Both predominantly used over-the-counter products, but "neuroenhancers" might be characterized by a higher propensity to instrumentalize over-the-counter products for virtually all investigated goals whereas "fatigue-fighters" might be inclined to use over-the-counter products exclusively to fight fatigue. We believe that psychological investigations like these are essential, especially for designing programs to prevent risky behavior. [FULL TEXT AVAILABLE]

The misuse and abuse of prescription medications: part 1 current trends Allread, V; Paul, S MD Advisor 7, 4, p.12-20, 2014

The epidemic of prescription drug abuse has triggered a resurgence in heroin abuse by young people. Heroin is a less-expensive analogue of prescription painkillers that delivers a stronger high and is currently more readily available than ever in areas with suburban and rural ZIP codes. The abuse and misuse of prescription medications and consequent heroin addiction have directly impacted rates of admission to drug treatment facilities; additional, injection may put users at risk of transmitting or acquiring blood-borne pathogens, particularly hepatitis C and HIV. This article reviews national and New Jersey- specific data on the misuse of prescription medications, the relationship between prescription painkillers and heroin use, some of the reasons why prescription painkiller sales have increased dramatically in the United States, the importance of screening for addiction and resources for referrals.

The misuse & abuse of prescription medications: part 2 the role of prescribing and New Jersey's response Paul, S; Allread, V MD Advisor 8, 1, p.4-14, 2015

A novel orvinol analog, BU08028, as a safe opioid analgesic without abuse liability in primates Ding H, Czoty PW, Kiguchi N, Cami-Kobeci G, Sukhtankar DD, Nader MA, Husbands SM, Ko MC Proceedings of the National Academcy of Sciences of the USA 29 August 2016 pii: 201605295 [Epub ahead of print]

Despite the critical need, no previous research has substantiated safe opioid analgesics without abuse liability in primates. Recent advances in medicinal chemistry have led to the development of ligands with mixed mu opioid peptide (MOP)/nociceptin-orphanin FQ peptide (NOP) receptor agonist activity to achieve this objective. BU08028 is a novel orvinol analog that displays a similar binding profile to buprenorphine with improved affinity and efficacy at NOP receptors. The aim of this preclinical study was to establish the functional profile of BU08028 in monkeys using clinically used MOP receptor agonists for side-by-side comparisons in various well-honed behavioral and physiological assays. Systemic BU08028 (0.001-0.01 mg/kg) produced potent long-lasting (i.e., >24 h) antinociceptive and antiallodynic effects, which were blocked by MOP or NOP receptor antagonists. More importantly, the reinforcing strength of BU08028 was significantly lower than that of cocaine, remifentanil, or buprenorphine in monkeys responding under a progressive-ratio schedule of drug self-administration. Unlike MOP receptor agonists, BU08028 at antinociceptive doses and ∼10- to 30-fold higher doses did not cause respiratory depression or cardiovascular adverse events as measured by telemetry devices. After repeated administration, the monkeys developed acute physical dependence on morphine, as manifested by precipitated withdrawal signs, such as increased respiratory rate, heart rate, and blood pressure. In contrast, monkeys did not show physical dependence on BU08028. These in vivo findings in primates not only document the efficacy and tolerability profile of bifunctional MOP/NOP receptor agonists, but also provide a means of translating such ligands into therapies as safe and potentially abuse-free opioid analgesics. Psychiatric disorders among patients seeking treatment for co- occurring chronic pain and opioid use disorder Barry, D T; Cutter, C J; Beitel, M; Kerns, R D; Liong, C; Schottenfeld, R S Journal of Clinical Psychiatry 7 September 2016 doi: 10.4088/JCP.15m09963 [Epub ahead of print]

Objective: Psychiatric comorbidities complicate treatment of patients with chronic pain and opioid use disorder, but the prevalence of specific comorbid psychiatric disorders in this population has not been systematically investigated. Methods: 170 consecutive participants entering a treatment research program for co- occurring chronic pain and opioid use disorder between March 2009 and July 2013 were evaluated with the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I/P) and the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV). Results: The prevalence of any lifetime (and current) comorbid Axis I disorder was 91% (75%); 52% met criteria for lifetime anxiety disorder (48% current), 57% for lifetime mood disorder (48% current), and 78% for lifetime nonopioid substance use disorder (34% current). Common current anxiety diagnoses were posttraumatic stress disorder (21%), generalized anxiety disorder (16%), and panic disorder without agoraphobia (16%). Common current mood diagnoses were major depressive disorder (40%) and dysthymia (11%). A majority of patients had a personality disorder (52%). Conclusions: High rates and persistence of co-occurring psychiatric disorders, including anxiety or mood disorders, may explain in part the difficulty providers have treating patients with co-occurring opioid use disorder and chronic pain and suggest possible targets for improving treatment.

Emergency visits for prescription opioid poisonings Tadros A, Layman SM, Davis SM, Davidov DM, Cimino S Journal of Emergency Medicine 49 (6) p.871-877, 2015

Background: Prescription opioid abuse and overdose has steadily increased in the United States (US) over the past two decades, and current research has shown a dramatic increase in hospitalizations resulting from opioid poisonings. Still, much is unknown about the clinical and demographic features of patients presenting to emergency departments (EDs) for poisoning from prescription drugs. Objective: We sought to evaluate ED visits by adults for prescription opioids. Methods: This was a retrospective cohort study utilizing 2006-2011 data from the Nationwide Emergency Department Sample. Total number of admissions (weighted), disposition, gender, age, expected payer, income, geographic region, charges, and procedures performed were examined. Results: From 2006 through 2010, there were 259,093 ED visits by adults for poisoning by opioids, and 53.50% of these were unintentional. The overall mean age of patients was 45.5 years, with more visits made by females (52.37%). Patients who unintentionally overdosed were more likely to have Medicare (36.54%), whereas those who intentionally overdosed had private insurance (29.41%). The majority of patients resided in the South (40.93%) and came from lower-income neighborhoods. Approximately 108,504 patients were discharged, and 140,395 were admitted. Conclusions: There were over 250,000 visits to US EDs from 2006 through 2011 with a primary diagnosis of poisoning by a prescription opioid. Females made the majority of visits, and over half were admitted to the hospital, resulting in over $4 billion in charges. Future studies should examine preventative measures, optimal screening, and intervention programs for these patients.

Not all high-dose opioid users are addicts Hirsch, R JAMA Internal Medicine 176, 9, p.1407, 2016

Not all high-dose opioid users are addicts - reply Katz, M H JAMA Internal Medicine 176, 9, p.1407, 2016

Treatment / Prevention

Pediatric group says doctors should treat teen opioid addicts with medicine http://www.usatoday.com/story/news/health/2016/08/22/pediatric-group-says- doctors-should-treat-teen-opioid-addicts-medicine/89042316/

States receive $53 million in grants to fight opioid epidemic http://www.drugfree.org/news-service/states-receive-53-million-grants-fight- opioid-epidemic/

Public Health / Policy / Legislation / Law Enforcement Getting high on elephant tranquilizer: Carfentanil reaches the U.S. http://www.pulseheadlines.com/high-elephant-tranquilizer-carfentanil- reaches/48466/

Drug linked to Ohio overdoses can kill in doses smaller than a snowflake Carfentanil, an animal tranquilizer, was believed responsible for many of more than 200 overdoses in the Cincinnati area over the past two weeks | NYTimes, USA http://www.nytimes.com/2016/09/06/us/ohio-cincinnati-overdoses-carfentanil- heroin.html?_r=0

Elephant tranquiliser being 'road tested' by US drug dealers http://news.sky.com/story/elephant-tranquiliser-being-road-tested-by-us-drug- dealers-10568782

Carfentanil: everything you should know about this deadly synthetic drug http://www.techtimes.com/articles/176454/20160906/carfentanil-everything- you-should-know-about-this-deadly-synthetic-drug.htm

Heroin mixed with powerful animal tranquilizer linked to spike in overdoses in Ohio https://consumerist.com/2016/09/06/heroin-mixed-with-powerful-animal- tranquilizer-linked-to-spike-in-overdoses-in-ohio/

Older adults employ high-risk methods to obtain opioids Sarah L. Gold, M.S.W., from the State University of New Jersey in New Brunswick, and colleagues analyzed cross-sectional survey data from the New Jersey Older Adult Survey on Drug Use and Health for 725 adults aged 60 years and older | Medical Xpress, USA http://medicalxpress.com/news/2016-09-older-adults-high-risk-methods- opioids.html

Is menopause to blame for painkiller addiction in women http://www.newbeginningsdrugrehab.org/prescription-drugs/is-menopause-to- blame-for-painkiller-addiction-in-women/

Rise in psychiatric drug prescribing due to overstretched GPs Harry Shapiro, director of DrugWise, said the rise in benzodiazepine-type drug prescriptions was, in part, due to a “hidden collusion” between stressed GPs and patients, looking for a prescription | Nursing in Practice, UK http://www.nursinginpractice.com/article/rise-psychiatric-drug-prescribing-due- overstretched-gps-says-charity-director

Risky alone, deadly together Overdosing on prescription drug combinations plays a part in the growing rates of premature death among white women | Washington Post, USA http://www.washingtonpost.com/sf/national/wp/2016/08/31/2016/08/31/opiods- and-anti-anxiety-medication-are-killing-white-american-women/

Study looks at criminal element of performance enhancing drug market among bodybuilders Many bodybuilders illegally sell steroids to help fund their own use of performance and image enhancing drugs and maintain their social status in the weightlifting community, a new academic study has found | News- Medical, USA http://www.news-medical.net/news/20160907/Study-looks-at-criminal- element-of-performance-enhancing-drug-market-among-bodybuilders.aspx

An alarming trend in newborns: mothers sharing their addictions https://www.clarityway.com/blog/mothers-sharing-addictions/

FDA requires strong warnings for opioid analgesics, prescription opioid cough products, and benzodiazepine labelling related to serious risks and death from combined use http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm51869 7.htm

FDA heightens warning about drug combinations Food and Drug Administration gets more insistent about dangers of opioids taken with sedative medicines http://www.wsj.com/articles/fda-heightens-warning-about-drug-combinations- 1472680199

Anti-depressants given to children soar by nearly 30 per cent in 10 years Study finds many doctors are prescribing a toxic drug to children despite official guidance not to do this unless other treatments fail | Independent, UK http://www.independent.co.uk/news/science/antidepressants-childhood- children-use-statistics-30-per-cent-10-years-unhappiness-a7231756.html

Brain fry: Perfectionism and attitudes about smart drug use College students who strive for high grades have a variety of overlapping reasons for studying and working hard. For some, college is a stepping stone to graduate school or a professional program, and a stellar transcript is crucial to getting into a top program | BASIS, USA http://bit.ly/2c2VY7m

Maker of deadly fentanyl kicks in half a million to defeat pot legalization in Arizona Big Pharma has long been accused of trying to block marijuana legalization http://www.alternet.org/drugs/maker-deadly-fentanyl-kicks-half-million-dollars- defeat-pot-legalization-arizona

A maker of deadly painkillers is bankrolling the opposition to legal marijuana in Arizona https://www.washingtonpost.com/news/wonk/wp/2016/09/09/a-maker-of- deadly-painkillers-is-bankrolling-the-opposition-to-legal-marijuana-in-arizona/