Management of Bipolar Disorder March 2016

Care Process Model MARCHMONTH 20152016

DEVELOPMENTMANAGEMENT OFAND DESIGN OF BipolarCare Process Disorder Models 20162015 Update

This care process model (CPM) was developed by Intermountain Healthcare’s Behavioral Health Clinical Program as part of a care management system for bipolar disorder. The CPM recommends screening, diagnosis, and treatment processes to improve care and outcomes for patients with bipolar disorder. Related tools — including evaluation forms, reference tools, and patient education handouts — support implementation of these recommended processes. WHAT’S INSIDE? UNDERSTANDING BIPOLAR Why Focus ON BIPOLAR DISORDER? DISORDER...... 2 • High prevalence. A 2005 report on National Comorbidity Survey Replication SCREENING AND DIAGNOSIS. . . .4 (NCS-R) data estimated that bipolar disorder affects about 5.7 million ALGORITHM 1: Diagnosis...... 4 American adults, or about 2.6% of the population 18 years and older (1-year Discussion: The need for consistent screening and diagnosis...... 5 prevalence).KES1 The same study noted a lifetime prevalence of 3.9%, suggesting TREATMENT FOR ADULTS. . . . .11 the chronic nature of this illness.KES2 ALGORITHM 2: Treatment ...... 11 • Inadequate detection. Estimates from surveys of people who screen positive Medications...... 12 for bipolar disorder note that clinicians misidentify their condition more Psychosocial Therapy ...... 19 FRY1, SUP1 Electroconvulsive Therapy (ECT). . . . 20 than half of the time. Patients may visit several clinicians before being Care Management ...... 20 correctly diagnosed. Many suffer for a decade or more before being diagnosed BIR FOLLOW-UP AND MAINTENANCE. .21 and appropriately treated. Misidentification leads to increased hospitalization Follow-up Schedule...... 21 BIR, HIR1, PEE and emergency room visits and higher healthcare costs. Remission and Maintenance...... 21 • Inappropriate use of antidepressants. When providers mistake bipolar Outcomes Assessment Tools ...... 22 depression for unipolar depression, they are likely to treat using only BIPOLAR DISORDER IN CHILDREN antidepressants.FRY1, HIR1, PEE In patients with bipolar disorder, using antidepressants AND ADOLESCENTS...... 24 Symptom expression...... 24 alone (unopposed by mood-stabilizing medications) can induce mania, mixed EIMA, GYU Differential diagnosis and states, and more severe rapid cycling varieties of this disorder. Medications comorbidity...... 25 with mood-stabilizing properties should be used to treat this illness. Treatment guidelines...... 25 • Poor treatment adherence. Patients with bipolar disorder typically have low PATIENT AND FAMILY EDUCATION. .28 adherence to treatment; reported non-adherence for long-term prophylactic RESOURCES AND REFERENCES. . .29 pharmacotherapy is about 40%.LIN Psychosocial interventions can significantly improve adherence. GOALS /MEASUREMENTS • Improve identification of bipolar • Risk of death. Bipolar disorder can be a debilitating disease with a high risk of disorder by promoting and measuring use GOO death by suicide (19%). People with this disorder rate their illness as “severe” of validated screening tools such as the Mood 83% of the time — much higher than they rate the severity of other mental Disorder Questionnaire (MDQ). illnesses (22%) — and have trouble functioning in many areas of life.KES2, EIMA • Improve treatment by reducing Treatment can significantly reduce suicide rates, even in those who are more the use of unopposed antidepressants and severely ill.ANG increasing appropriate use of mood stabilizers. • Improve outcomes assessment using • Lost productivity. According to a recent study funded by the National both symptom-specific and functional Institute of Mental Health (NIMH), bipolar disorder costs the U.S. workplace measures to determine treatment impact. $14.1 billion annually; this is nearly half as much as lost-productivity costs due Throughout this CPM, the icon at right to unipolar depression, although unipolar depression is more than six times as indicates an Intermountain measure. prevalent.KES3 Over the past 20 years, the World Health Organization (WHO) has consistently rated bipolar disorder among the top 10 leading causes of disability in the world.WHO MANAGEMENT OF BIPOLAR DISORDER MARCH 2016

DIMENSIONS OF IMPAIRMENT UNDERSTANDING BIPOLAR DISORDER • Moods. Extreme mood episodes are the hallmark of this disorder. Bipolar disorder, previously called manic-depressive disorder, is a chronic biological disease, not a character defect or moral failing. People with this illness experience • Thoughts. Several studies detail cognitive changes in their mood and ability to think and to function. At other times they can be impairment in bipolar disorder—in completely without signs or symptoms of their illness. Depression is the most common particular, problems with memory and mood in bipolar disorder but people also experience hallmark periods of euphoria and executive function, attention and verbal skills.NOR irritability. It is not unusual for these mood states to overlap and profoundly disrupt a person’s work, school, home, and social life. The risk of suicide for this illness is very • Actions. Impulsivity and excessive high but does decrease with treatment.ANG risk-taking are common, especially during episodes of mania. People can find Genetic basis themselves acting in ways that aren’t characteristic for them and don’t represent The exact cause of bipolar disorder is not known. Recent studies have identified that their personal values. Excessive spending, a patient’s genetic predisposition to the disorder may derive from those genes that are sudden travel, uncharacteristic substance involved in hormone regulation, calcium channels, secondary messenger systems, and NUR abuse and sexual promiscuity are common glutamate signaling. The risk of bipolar disorder increases if a parent or sibling suffers CRA, LIC expressions of bipolar impulsivity. from the disorder. First-degree biological relatives of someone with bipolar I disorder have a 4 – 24% chance of developing bipolar I disorder, a 1 – 5% chance of developing bipolar II disorder, and a 4 – 24% chance of having unipolar depression.APA1 When one identical twin has bipolar disorder, the other twin is 7 – 8 times more likely MAJOR TYPES OF KIE, MCG BIPOLAR DISORDER to have it than a fraternal twin. Bipolar depression versus unipolar depression Bipolar I Disorder: Diagnosis requires at least one lifetime Depressive symptoms are the most common in bipolar disorder. They can appear manic or mixed episode (causing significant identical to those of a person with unipolar depression. More than 10% of patients with impairment); most people with bipolar I depression will go on to experience a mania or hypomania episode in the next decade. AKI have also had one or more episodes of Unlike unipolar depression, which is more common in women than men, bipolar I APA1 major depression. disorder is equally common in men and women. • Discriminators of unipolar versus bipolar depression: Factors suggestive of bipolar Bipolar II Disorder: depression include an onset before the age of 25, a parent or sibling with bipolar Diagnosis requires at least one lifetime disorder, a history of psychotic depression, postpartum depression, multiple recurrent episode of hypomania (causing less significant depressive episodes, or a history of mania or hypomania induced by antidepressants. impairment) and at least one episode of Further, bipolar depression is often associated with “atypical” symptoms including major depression. hypersomnia and hyperphagia. Depression frequently occurs with partial or complete PER Cyclothymia: mania symptoms such as racing thoughts, irritability, impulsivity, and psychosis. • Diagnosis requires at least 2 years (only Predictors of progression from unipolar to bipolar I or II depression: Among patients 1 year in children and adolescents) of who have major depression and go on to develop bipolar disorder, a more acute, clinically significant distress/impairment in severe, and psychotic episode predicts bipolar I disorder (about 4% of depressives key areas of functioning (at work, at school, followed long term) and mood lability or temperamental instability predicts bipolar II AKI at home, with friends, etc.). This period is disorder (about 9% of depressives followed long-term). characterized by numerous periods where the person experiences hypomanic and depressive Bipolar spectrum symptoms that fail to meet the full criteria of Bipolar disorder and unipolar depression seem to exist at two ends of a spectrum. either hypomania or major depression. In the middle of the spectrum are patients with major depression and some symptoms associated with bipolar disorder (e.g., racing thoughts). These patients have more risk factors of bipolar disorder (e.g., early age of depression onset and family history) than those suffering unipolar depression without those symptoms. If these patients do not respond to standard depression treatment, clinicians should consider medications with mood stabilizing properties. Family history studies support this view of the bipolar spectrum. Patients with bipolar I disorder may have offspring with bipolar I, bipolar II, or unipolar depression, whereas patients with bipolar II disorder tend to have offspring with bipolar II or unipolar depression.BEN

Variety in symptom expression WHAT IS MANIA? The average age of onset of bipolar disorder is in the teen years to early 20s.KES2 The Mania is defined as a mental state first episode can be either a depressive or manic episode. Transitioning from a characterized by rapid thoughts, irritable/ manic/hypomanic episode to a depressive episode or from a depressive episode to a euphoric mood, increased activity, manic/hypomanic is considered one “cycle” of bipolar disorder. The episodes in each talkativeness, and/or impaired judgment. cycle can vary from mild to severe in intensity. They can be interspersed by long periods Manic or hypomanic patients exhibit these of euthymic mood or be followed immediately by another mood cycle. Disability in types of symptoms: functioning is usually related to how frequently people cycle and how severe their • Activity or stimulation: Symptoms symptoms are during their cycle. are similar to those experienced when one takes excessive doses of stimulant • Proportion of time spent in various mood states. People with bipolar disorder medications, such as euphoria and suffer reoccurring mood symptoms throughout their life. One study tracked patients’ irritability. Actions and feelings are also moods weekly for over a decade for the two major types of the illness (bipolar I stimulated: a manic patient may need disorder and bipolar II disorder). In this study, most of the time symptomatic was less sleep, have increased speed of JUD1,JUD2 spent depressed and a minority of time was spent either manic or hypomanic. thoughts, speak faster or with pressure, These results are shown below: have increased focus on activities, and be overtly agitated. Increased activity can Cycling/Mixed Manic/Hypomanic Cycling/Mixed range from doing a routine task excessively, (6%) (1%) (2%) such as doing housework all night long, Manic/Hypomanic to becoming involved in uncharacteristic (9%) Asymptomatic Asymptomatic activities, such as planning multiple risky Depressed (53%) Depressed (46%) business ventures. (32%) (50%) Bipolar I Bipolar II • Intensity: Mania symptoms are 146 patients 86 patients experienced with heightened intensity. followed 12.8 years followed 13.4 years They may be intensely pleasurable or intensely dysphoric. • Severity of symptoms. Over the long-term course, the majority of symptoms • Impaired judgment and thinking: are subsyndromal or not severe enough to diagnose as major depression or as overt Behavior and actions are often mania. Nevertheless, subsyndromal depressive symptoms can be significantly impulsive and pleasure-seeking. When disabling. Hypomanic episodes are often rated by patients as causing no disability manic, patients can participate in (and some feel it to be a state of superior functioning). Severe manic symptoms are as uncharacteristic overspending, promiscuity, disabling as severe depressive symptoms. substance abuse, or other impulsive • Combinations of symptoms. It is common to have symptoms of mania/ behavior. Judgment may be affected by hypomania and depression at the same time. An estimated 40% of manic episodes perceptual disturbances such as auditory and more than half of all hypomanic episodes are associated with significant hallucinations, thought problems such as depressive symptoms.SUP2 Some people with bipolar disorder experience mixed paranoia, flight of ideas (ideas that change states — episodes in which they have symptoms that meet criteria for both mania so rapidly that they are confusing), or false and depression nearly every day for a 1-week period or longer. Mixed episodes beliefs (e.g., that one is more powerful, are common and can be very severe. They are also associated with less frequent famous, or successful than in reality). Over half of patients who have bipolar disorder remissions, poorer response to mood stabilizers, increased suicidal ideation/behavior, experience psychotic symptoms at some and more comorbidities (including substance abuse). Use of antidepressants is also time during their illness.GOO associated with increased incidence of mixed episodes.HIR1, GOL1, PRI, SHA • Frequency of episodes. Cycling varies from an average of 1 cycle every 3 years to the severe variation called rapid cycling. Rapid cycling is when people cycle between mood episodes four or more times a year. This variety can be either bipolar I or bipolar II. The typical patient is bipolar II and female. In this variant, there appears to be a continuous distribution from limited mood cycling to the extreme of intra- day (ultraradian) cycling. This form of the illness may be less sensitive to the effects of lithium carbonate. Factors associated with rapid cycling include the following:GOL1, PRI, SHA, HIR2, SCHN –– Female gender and early life trauma (more strongly associated with cycling between mood states more than once a month) –– Antidepressant use –– Genetic susceptibility (higher prevalence of the double short allele of the serotonin transporter protein) –– Clinical or subclinical hypothyroidism

The variables noted above should be considered when diagnosing bipolar disorder — and when treating it . Medication(s) can alter the expression of the disorder .

ALGORITHM NOTES SCREENING AND DIAGNOSIS (a) PHQ-2 Scoring ALGORITHM 1: DIAGNOSIS The PHQ-2 consists of the first two questions in the PHQ-9 (see page 5) used as a first step in screening patents for depression. Scoring Patient appointment with Patient appointment with for each question is indicated below: mental health specialist primary care provider

TABLE 1. PHQ-2 Scoring ADMINISTER and SCORE the first two questions of Score* based on patient response to the Patient Health Questionnaire (PHQ-2) (a) each item below: Over the past 2 weeks, how often have you been bothered by any of the fol- Positive? no PROVIDE usual care lowing problems? yes Item Score Range* ADMINISTER and SCORE the Patient Health Little interest or pleasure in 0 – 3 Questionnaire (PHQ-9) to identify and doing things diagnose major depression (see page 5) (b) Feeling down, depressed or 0 – 3 hopeless Total Score (Positive = ≥ 3) 0 – 6 Positive? no PROVIDE usual care *Score based on the following: 0 = Not at all; 1 = Several Days; 2 = > Half the Days; 3 = Nearly Every Day yes ASSESS suicide risk and DETERMINE associated Question 9 yes treatment (b) PHQ-9 Scoring *NOTE: the score from the Positive?* (see page 5 and Suicide Prevention CPM) The PHQ-9 (see page 5) uses both a symptom PHQ-9 does not override no score and a severity score. Scoring guidance clinical judgment. for each type is indicated below:

TABLE 2. PHQ-9 Scoring ADMINISTER and SCORE(c) the Mood Disorder Questionnaire (MDQ) (see page 6 (c) Measure Scoring Guidelines Symptom Score ≥ 5 = Administer MDQ (see page xx) TREAT per < 5 = Usual care; see Depression no Positive?Positive? Depression cpm. CPM yes Severity Score ≥ 9 = Administer MDQ (see page xx) < 9 = Usual care; see •• INTERVIEW patient to confirm specific DSM-5 diagnostic criteria. Depression cpm. •• USE SADFIGS mnemonic to aid diagnosis (see page 7). Suicidal Ideation If “yes” to question #9, •• RATE severity of illness with CGI Scale (see page 22). assess suicide risk.

(c) MDQ Scoring ASSESS for comorbidities (see page 8) Score the MDQ according to the criteria below Mental health specialist Primary care provider and guidance in the Scoring and Evaluating Adult MHI Forms CPM. For a positive screen, all three of the •• REFER to a mental health specialist if patient has unmanageable conditions or behaviors such as significant following criteria must be met: TREAT per comorbidities, psychotic tendencies, suicidal ideation/behavior, algorithm • Question 1: 7 / 13 positive (yes) responses on page 10 violence, or treatment failures. • Question 2: Positive (yes) response •• START treatment (using a medication with mood-stabilizing properties per algorithm on page 11) while awaiting mental • Question 4: “moderate” or “serious” health referral or consultation. response •• DO NOT USE UNOPPOSED ANTIDEPRESSANTS.

Discussion: The need for consistent screening and diagnosis Patients with bipolar disorder may see multiple healthcare providers for as many as 10 years or more before they receive the correct diagnosis. This is due in part to these factors: • People with bipolar disorder seek treatment more often when depressed, and thus they are often treated for unipolar depression. • Bipolar disorder is often comorbid with substance abuse and anxiety disorders, which can mask and complicate symptoms. Thus, assessing for comorbidities is a critical part of the screening process (see pages 9 – 10). • There is often no consistent process for screening and diagnosis in various care settings. Primary care providers (PCPs) are generally the first care providers who see a patient with bipolar disorder. Unfortunately, since patients often present with symptoms of depression, bipolar disorder is often misdiagnosed as unipolar depression and treated inappropriately with an unopposed antidepressant, which can make the illness worse. You can download the PHQ-9 Unopposed antidepressants may induce mania and mixed bipolar states, mood at: https://m intermountain. .net/forms/ instability, and rapid cycling. Pages/Details .aspx?isForm=true&ncid=52 1377846&title=MHI PHQ-9 Patient Health Patients eventually diagnosed with bipolar disorder often experience multiple failed Questionnaire antidepressant trials or the onset or worsening of agitation and anxiety while on antidepressants.FRY1, SUP1, BIR, HIR1, PEE To improve early identification and treatment of bipolar disorder, this CPM recommends a consistent process for screening and diagnosis in all treatment settings. This includes use of validated screening tools such as the Patient Health Questionnaire (PHQ-9) for depression and suicidal ideation and behavior (content appears at right) and the Mood Disorder Questionnaire (MDQ) for mania (content appears on page 6).HIR3

Suicide assessment As shown in the algorithm on the previous page, an assessment of suicide risk should be done for every patient who responds positively to question 9 on the PHQ-9 or who has experienced suicidal ideation (thoughts of engaging in suicidal behavior). Although suicide is a low-probability event, bipolar disorder is one of the most common psychiatric disorders associated with suicide.PAL, SAR Patients with bipolar disorder have a high rate of lifetime suicide completion (about 19%).GOO Intermountain uses the Columbia-Suicide Severity Rating Scale (C-SSRS) to standardize assessment of suicidal ideation and behavior, determine levels of risk, and make clinical decisions about care. TheSuicide Prevention CPM details the C-SSRS versions used and suggested treatment approaches in each care setting. The table below (from page 3 of theSuicide Prevention CPM) provides an overview of risk level (based on a positive response to each C-SSRS Quick Screen question and recommended actions to take in each setting based on patient responses. See the Suicide Prevention CPM for detailed steps for asking these questions.

TABLE 3: Patient safety measures and response protocols based on Quick Screen responses C-SSRS Quick Screen questions Action if patient response “Yes” (in the last month) Question “Yes” Level of risk Outpatient clinic ED at triage Inpatient care indicates (non-BH) For identified BH patients BH unit

1. Have you wished Wish to LOW •• Consider referral to •• Consider referral to •• Continue with •• Continue with you were dead or be dead MHI or BH provider MHI or BH provider plan of care plan of care wished you could •• Consider patient at discharge from ED go to sleep and education •• Consider patient not wake up? education 2. Have you actually Nonspecific had any thoughts thoughts of killing yourself?

3. Have you been Thoughts MODERATE •• Assess risk factors •• Initiate nursing •• Continue with thinking about with method and either facilitate interventions (e.g., plan of care how you might (without evaluation for secure belongings) •• Initiate nursing interventions kill yourself? specific plan or inpatient admission •• Order crisis intent to act) or complete Safety worker evaluation Plan with follow-up •• Psychiatric consult in 24 – 48 hours recommended •• Educate patient 4. Have you had Intent HIGH •• Facilitate immediate •• Initiate nursing •• Notify charge nurse/shift •• Notify charge these thoughts (without plan) evaluation interventions coordinator nurse/shift and had some •• Educate the patient •• Order PSA until •• Notify attending physician coordinator intention of acting crisis worker •• Assess need for 1:1 •• Notify attending on them? evaluation complete physician •• Initiate nursing interventions • Notify ED physician • Assess need 5. Have you started Intent • •• Administer C-SSRS Lifetime/ • to work out or with plan •• Order crisis worker Recent Assessment for 1:1 worked out the evaluation (Adult/Adolescent details of how to •• Psychiatric consult or Pediatric) kill yourself? Do highly recommended you intend to carry out this plan?

6. Have you ever Behavior >1 year ago: LOW •• Consider referral to MHI or BH provider done anything, •• Consider patient education started to do anything, or 1 – 12 months ago: •• Assess risk factors •• Order crisis worker •• Assess risk factors and consider referral to MHI prepared to do MODERATE and refer to MHI or evaluation or BH provider anything to end BH provider •• Psychiatric consult •• Initiate nursing interventions your life? •• Educate patient recommended Past 4 weeks, during •• Facilitate immediate •• Order crisis worker •• Notify charge nurse/shift •• Notify charge current inpatient stay, evaluation for evaluation coordinator nurse/shift since last assessment: inpatient care •• Initiate nursing •• Notify attending physician coordinator HIGH •• Educate patient interventions •• Assess need for 1:1 •• Notify attending physician •• Order PSA •• Initiate nursing interventions •• Psychiatric consult •• Assess need highly recommended for 1:1

Mood Disorder Questionnaire (MDQ) WHEN TO SCREEN The Mood Disorder Questionnaire (MDQ) is a tool that screens specifically for • In primary care settings: Primary care bipolar disorder. It is NOT a diagnostic instrument. Used alone in a population with providers should screen all new patients for depression with the PHQ; patients who low rates of bipolar disorder (e.g., in primary care settings), it will produce significant screen positive for depression should be false positive results. Therefore, screening an enriched population, such as those who further screened with the MDQ. meet diagnostic criteria for depression and/or have failed an antidepressant trial, or • In mental health provider settings: Mental Health Integration Adult those for whom the clinician intuits bipolar disorder, is likely to correctly identify Mental health specialists should screen all the most patients. (Note that patients who have a negative result using the MDQ are new patients with the MDQ. Mood Disorder Questionnaire (MDQ) (page 1 of 1) unlikely to have bipolar disorder.) Content of the MDQ form appears below; see the Today’s Date: Patient’s Name: Date of Birth: notes at right for tips on using and interpreting the tool. YES NO INTERPRETING RESULTS 1 Has there ever been a period of time when you were not your usual self and… For a positive screening, questions 1 and 2 … you felt so good or so hyper that other people thought you were not your normal self, must both be positive: or you were so hyper that you got into trouble?

… you were so irritable that you shouted at people or started fights or arguments? • For question 1, a positive result is 7 or more of the 13 sub-questions answered … you felt much more self-confident than usual? “yes.” … you got much less sleep than usual and found you didn’t really miss it? • For question 2, a positive result is “yes.” … you were much more talkative or spoke much faster than usual? • Question 3 measures potential for … thoughts raced through your head or you couldn’t slow your mind down? medication-induced symptoms. … you were so easily distracted by things around you that you had trouble concentrating • or staying on track? Question 4 measures impairment. A response of “moderate” or serious”

… you had much more energy than usual? suggests bipolar I disorder, whereas a … you were much more active or did many more things than usual? response of “minor” or “no problem”

… you were much more social or outgoing than usual; for example, you telephoned friends suggests bipolar II disorder. (See the

in the middle of the night? following page for more detail on distinguishing these 2 bipolar variants.) … you were much more interested in sex than usual?

… you did things that were unusual for you or that other people might have thought were

excessive, foolish, or risky? IMPROVING SENSITIVITY … spending money got you or your family into trouble? Adding the following 2 sub-questions 2 If you checked YES to more than one of the above, have several of these ever happened during to question 1 of the MDQ can improve the same period of time? the sensitivity of the MDQ screening by 3 During the period of time indicated above, do you think any of these symptoms were brought on as much as 10% (as suggested by 2007

by prescription or other drugs? Intermountain Healthcare data): 4 How much of a problem did any of these cause you — like being unable to work; having family, money, or legal troubles; or • Have any close family members (parents, getting into arguments or fights? siblings, children) ever been diagnosed with no problem minor problem moderate problem serious problem bipolar disorder or manic depression?

For Office Use Only: • Did you have mood problems before the / 13 age of 25? WhatReprinted with next? permission from the American Journal of Psychiatry, (Copyright 2000). American Psychiatric Association. *50402* When these two questions are added to the ©2004–2014 Intermountain Healthcare. All rights reserved. When a patient screens positive for bipolar disorderMHI Pack 50402 using the MDQ: 13 items in section 1, patients who answer Patient and Provider Publications 801-442-2963 MHI019 - 10/14 “yes” to <6 of the 15 questions are very • Interview the patient to determine if the patient has had at least one lifetime unlikely to have bipolar disorder. episode of depression and one lifetime episode of mania or hypomania. • Use DSM-5 diagnostic criteria to determine and confirm a diagnosis (see page 8).

A MNEMONIC TO AID Diagnostic criteria DIAGNOSIS: The table below provides an overview of key diagnostic criteria for bipolar 1 disorder, SADFIGS bipolar II disorder, and cyclothymic disorder — the most prevalent bipolar disorder For confirmation of a lifetime episode of diagnoses. mania or hypomania — and a bipolar TABLE 4: Overview of Major1 Bipolar DiagnosesAPA1 disorder diagnosis — a patient’s symptoms must meet these criteria: Episode Context1 Duration2 Severity3 • A consistently elevated, irritable, or Type(s) expansive mood lasting at least 1 week 1 (or any duration if hospitalization is (Required) required) for mania and at least 4 days Manic Lifetime 1 week; almost Impacts all key areas of

for hypomania. daily; >50% of functioning, includes each day psychotic features, • If elevated mood, at least three of the or necessitates following SADFIGS symptoms. If irritable Bipolar I of page for hospitalization mood, at least four of the following ICD-10 codes) SADFIGS symptoms: at bottom (see box

Hypomanic AND Lifetime 4 days; almost Functioning is not seen major depressive daily; >50% of as usual for patient by Sleep, less need each day others in key areas; no S psychotic features; no

Bipolar II hospitalization needed Agitation or increased A FS31.81) (ICD-10: focused activity Symptoms related Lifetime or Past 2 years Impacts key areas of D Distractibility to hypomanic AND past 2 years? (1 year if child or functioning and causes major depressive adolescent); 50% considerable distress BUT not meeting of overall time; F Flight of ideas or racing thoughts full criteria for either symptom free episode as defined by < 2 months within Cyclothymia I Impulsivity FS34.0) (ICD-10: DSM-5 time frame

G Grandiosity 1. For information related to other bipolar diagnoses (substance/medication-induced bipolar and related disorders, bipolar and related disorders due to another medical condition, and other specified bipolar and related disorders), see Diagnostic and Statistical Manual of Mental Disorders — Fifth Edition.APA1 Speech, rapid or pressured S 2 . Context: time frame in which symptomatic episode must have occurred (e.g., lifetime, past 2 years, etc.) 3 . Duration: specific number of days that symptoms occurred; symptoms last for a specified time and frequency during those days 4 . Severity: symptoms are severe enough to cause patients considerable distress and impact their daily functioning in key areas of their lives

ICD-10 CODING FOR BIPOLAR I Diagnostic coding for bipolar I is typically based on current or most F31.6 Bipolar disorder, current episode mixed (specify severity and recent episode and severity. General ranges appear in this box. For more presence of psychotic features) detailed coding instructions, refer to ICD10data com. . F31.7_ Bipolar disorder, currently in remission (specify full or partial F31.0 Bipolar disorder, current episode hypomanic remission and type of most recent episode) F31.1_ Bipolar disorder, current episode manic without psychotic F31.8 Other bipolar disorders (F31.81 Bipolar II disorders; F31.89 other features (specify severity) bipolar disorder) F31.2 Bipolar disorder, current episode manic severe with psychotic F31.9 Bipolar disorder, unspecified features

F31.3_ Bipolar disorder, current episode depressed mild or moderate NOTE: ICD-10 codes do not correspond exactly to DSM-5 severity (specify severity) codes and explanations. Intermountain‑employed providers F31.4 Bipolar disorder, current episode depressed, severe without can access an online version of the DSM- through the eResources psychotic features page on IntermountainPhysician.org or Intermountain .net . F31.5 Bipolar disorder, current episode depressed, severe with psychotic features

Comorbidities OTHER COMORBIDITIES/ Those with bipolar disorder typically suffer from at least one comorbid medical DIFFERENTIAL DIAGNOSES or psychiatric disorder (some studies indicate a large number of patients having at • Attention deficit hyperactivity least three chronic medical conditions) as well as having higher lifestyle risk factors disorder VA that occur at a younger age. These comorbidities can confuse and confound • Disruptive mood dysregulation diagnosis and treatment and also make the disorder more severe and difficult to disorder treat. Comorbidities are associated with increased emergency room visits and • Eating disorders more hospitalizations.NOR, GOL2 The most common mental health comorbidities are • Intermittent explosive disorder described below; medical comorbidities are discussed on page 10. • Major depressive disorder Mental Health Comorbidities • Personality disorders including borderline The most common comorbid mental health conditions are anxiety disorders and personality disorder substance use disorder. When co-occurring major psychiatric illnesses and/or For complete differential diagnosis significant suicidal ideation/behaviors or homicidality are present, clinical guidelines information on these disorders, see the Diagnostic and Statistical Manual of Mental emphasize the importance of referring these patients to specialty care (see also suicide Disorders — Fifth Edition.APA1 assessment information on page 6).VA Anxiety disorders. Anxiety disorders are the most common mental health comorbidities in patients with bipolar disorder — nearly 75% of patients have comorbid bipolar disorder and some type of anxiety disorder.KES4 Common features of anxiety include panic attacks, fears, and worries. Somatic symptoms include poor concentration, agitation, muscle tension, headache, and perspiration. It may be difficult to differentiate agitation caused by mania from anxiety caused by a comorbid anxiety disorder. Anxiety symptoms may be difficult to separate from symptoms of agitation while a patient is experiencing mania. What to do: Treat the bipolar disorder first; treatment may take care of anxiety symptoms. Substance use disorder. Substance use disorder is the second most common comorbid diagnosis in bipolar disorder.KES4, WEI More Intermountain-Modified National Institute than half of patients with bipolar disorder will on Drug Abuse (NIDA) Quick Screen have a substance use diagnosis in their lifetime. Substance use disorder includes alcoholism, tobacco use, prescription drug abuse, and “street drug” abuse. Alcoholism is the most common of In the past year, how often have you used the following? the substance use comorbidities.WEI The incidence of alcoholism in those with bipolar disorder Never Once or Twice Monthly Weekly Daily or Almost Daily • For men, ≥5 standard drinks* a day is 3 times higher for men and 7 times higher Alcohol:      for women.FRY2 • For women, ≥4 standard drinks* a day What to do: Use the NIDA Quick Screen Tobacco products (including e-cigarettes)      (download the full-size version of this tool here: Prescription medications for non-medical reasons      Intermountain-Modified NIDA Quick Screen to Prescription medications in amounts greater than screen for substance use disorder. If identified, prescribed, for reasons other than prescribed, or that      aggressively treat the substance use disorder weren’t prescribed to you

concurrently with bipolar disorder based on the Illegal drugs (illicit, street drugs)      Substance Use Disorder CPM. Successful treatment

of bipolar disorder is unlikely with ongoing • Beer or cooler (5% alcohol): 12 ounces • Malt liquor (7% alcohol): 8–9 ounces substance-use problems. Avoid lithium as a *Definition of a “standard drink:” primary mood stabilizer in these patients, and use • Table wine (12% alcohol): 5 ounces • 80-proof spirits (hard liquor) (40% alcohol): 1.5 ounces habit-forming sedatives with caution.

Copyright © 2014 American Medical Association. All rights reserved. *50053* © 2015 Intermountain Healthcare. All rights reserved. BH Pln50053 Patient and Provider Publications 801-442-2963 SUD006 - 01/15 MANAGEMENT OF BIPOLAR DISORDER MARCH 2016

THE IMPORTANCE OF Medical comorbidities INTERDISCIPLINARY Medical problems can not only cause mood episodes but can exacerbate the course of COLLABORATION bipolar disorder and complicate treatment in terms of greater illness severity, reduced For patients with bipolar disorder and recovery, and increased or premature mortality. These comorbidities often accentuate other medical conditions, early and regular psychological stressors related to employment and disability reimbursement and screening for comorbidities and careful increase healthcare utilization.VA medication management is crucial. For example, corticosteroids used to treat Major medical comorbidities in patients with bipolar disorder include cardiovascular asthma and inflammatory disease and disease, autoimmune diseases, cancer, and metabolic disorders. Of these, metabolic stimulants can be associated with secondary disorders (especially diabetes and obesity) offer significant challenges, in part due to mania. Taking diuretics and angiotensin- the weight-gain side effects of many medications used to treat bipolar disorder. In coverting enzyme inhibitors with lithium in patients with kidney disease or hypertension addition, there are significant challenges of care associated with comorbid diabetes, VA may complicate bipolar disorder treatment. including: Careful consideration of medications • Almost double the overall health care costs for bipolar patients who have diabetes that tend to promote weight gain is also • Greater impairment in both physical and mental health important. Referrals to a registered dietitian nutritionist (RDA) can be helpful in dealing • Lower quality of life with dietary intake and glycemic load. • Less satisfaction with health According to recent research, there is a bi-directional relationship between comorbid metabolic disorders and bipolar disorder because those with bipolar disorder tend to take in more calories with a higher glycemic load and are significantly more sedentary than the general population.MAN In addition, a 2012 population-based study of 800,000 people indicated that those with untreated type 2 diabetes had a significantly increased risk of developing bipolar disorder and that treating diabetes may prevent bipolar onset.MAN Other medical comorbidities can include thyroid dysfunction, migraines, and cardiovascular disease. Considerations include: • Thyroid dysfunction. Hypothyroidism is associated with rapid cycling and difficult-to-treat depression, and hyperthyroidism can produce agitation and anxiety that can make the identification of mania more difficult. • Other medical comorbidities lead to additional disability and mortality for bipolar patients. Note that compared to people without bipolar disorder:CAS, ELM, MAH, SCHI, WEE –– Incidence of migraines is 5 times higher. –– Incidence of cardiovascular disease is 1.9 times higher. What to do: Assessment for bipolar disorder must include assessment for the medical the conditions above. Patients should be treated concurrently — and extra monitoring may be necessary. Many medications used to treat this illness can aggravate cardiovascular risk factors (cardiovascular disease is the leading cause of death in patients with bipolar disorder).

TREATMENT FOR ADULTS Patients with bipolar disorder have better outcomes with aggressive, multimodal treatment that includes appropriate medication, patient/family education, psychotherapy, and (when available) care management. The target for treatment is FULL REMISSION. Patients who achieve remission will have lower rates of relapse. To assess progress toward this goal, providers should have a consistent method — such as the CGI scores described on page 18 — to assess response to treatment. Note that because of limited quality studies comparing treatment outcomes, the guidelines presented in this CPM are reasonably broad and focus primarily on bipolar I disorder. There is little quality evidence to support specific treatments for bipolar II disorder, and no published research for bipolar not otherwise specified (NOS). The algorithm below and the discussion and tables that follow present a recommended approach to treatment based on the best available evidence, along with expert opinion from clinical practice.

ALGORITHM 2: TREATMENT Patient diagnosed with bipolar I or bipolar II

Bipolar depression: START monotherapy with a medication *Note: In emergency situations with with mood stabilizing properties* acute symptoms, rapid titration and START with ONE of these: more than one medication may be START with a mood stabilizer with “A” quality data for • Quetiapine necessary to reduce time to response. treatment of the appropriate pole . • Lamotrigine However, lamotrigine should never be See the medication tables on pages 13 – 16 for details . • Lurasidone rapidly titrated due to increased risk of • Olanzapine + fluoxetine allergic rash. Mania/mixed mania: • PROVIDE patient/family education (see pages 27 – 28) • REFER for psychotherapy START with: • CONSIDER care management • Lithium carbonate (mania) OR FOLLOW UP in 1 – 2 weeks Divalproex sodium (mania/mixed) as indicated by acuity and severity OR • An atypical antipsychotic: no ADD a second mood stabilizer . • Aripiprazole • Ziprasidone Adequate response? • Olanzapine • Lurasidone yes • Quetiapine • Asenapine • Risperidone (Somewhat or much improved CGI global improvement score 1 – 3) For moderate to severe symptoms: FOLLOW UP in 4 weeks until remission. At every • COMBINE lithium and valproic follow-up visit: acid with each other OR with an • EVALUATE adherence atypical antipsychotic • ASSESS clinical response and side effects at current dose • CONSIDER the combination of • USE outcome measures to assess progress (see page 22) olanzapine and fluoxetine • ASSESS educational needs (Symbyax), which is FDA • ASSESS therapeutic alliance (see page 21) approved for bipolar 1 depression . • ASSESS for substance abuse (see page 9)

Improved?

Much improved Somewhat improved No improvement or worsening CGI score 1 – 2 CGI score 3 CGI score 4 – 7 • CONTINUE at present dosage(s) . • RAISE dose as tolerated; if at • RAISE dose of mood stabilizer maximum dose, change to a • FOLLOW UP every 4 weeks until as tolerated . remission (CGI severity score 1 – 2) . different primary mood stabilizer . OR OR • When in remission, FOLLOW UP at least • ADD a second mood stabilizer every 6 months to monitor symptoms, lab • ADD a second mood stabilizer focused on specific symptoms focused on specific symptoms values, and functional outcomes . • CONSIDER consultation/referral to a mental health specialist

TARGET: FULL REMISSION (CGI severity score 1 – 2)

THE 3 Ms OF MEDICATION Medications MANAGEMENT FOR BIPOLAR Because bipolar disorder is a recurrent and chronic illness, long-term DISORDER pharmacotherapy is almost always indicated. Optimizing medication for people Mood stabilizers with bipolar may require some trial-and-error to balance medication effectiveness with the associated side-effect burden. Overall, this process should be driven by In general, people with bipolar disorder should be treated with mood stabilizers the best scientific evidence possible — starting with FDA approved treatments or for extended periods of time (years). Other treatments that have shown positive effects in large controlled trials. Medication medications are added when necessary, recommendations (detailed on pages 13 – 18) are based on the strength of evidence typically for shorter periods, to treat episodes derived from review of literature, product package inserts, and experience from of mania or depression that break through clinical practice. despite the mood stabilizer. NOTE: if antidepressants are Mood stabilizers prescribed, mood-stabilizers must be continued as well. Medications with mood-stabilizing properties are the mainstay of treatment for bipolar disorder. Mood stabilization happens when a medication effectively treats at Multiple medications least one pole of bipolar disorder without worsening the opposite pole. Medications Studies indicate that most patients will with mood-stabilizing properties are a heterogeneous group that can be categorized need more than one medication to achieve by drug class and by whether they best treat mania, depressive symptoms, or both. remission.GIT Expert consensus guidelines suggest adding a second medication The group includes the following: after 1–2 weeks of inadequate response • Anticonvulsants, including carbamazepine, divalproex, lamotrigine, and oxcarbazepine to one medication or for moderate-to- severe symptoms.APA2, KEC Combining lithium • Lithium carbonate or divalproex sodium with an atypical • Atypical antipsychotics, including aripiprazole, asenapine, lurasidone, olanzapine, antipsychotic can be effective.MOL However, quetiapine, risperidone, and ziprasidone mixing atypical antipsychotics has no clinical research to support its efficacy and may Providers should choose a mood-stabilizing medication based on whether the patient increase the impact of shared side effects. presents with depression, mania, or a mixed state — and on the severity of symptoms. Because of significant side effects, careful monitoring is important for patients taking Monitoring mood stabilizers. Tables 6A and 6B on page 16 detail recommended monitoring for Because using multiple medications increases each medication/class. Preference should be given to a mood stabilizer intended for side effects, complicates treatment, and worsens patient compliance, monitor maintenance; some medications are better at preventing mania and some are better at patients carefully for these problems. See preventing depressive relapse (see information on use in table 5 on pages 13 – 15). the treatment algorithm on page 10 and the medication table at right for specific Antidepressants considerations. In addition, monitoring Although bipolar disorder is mostly a depressive illness, evidence indicates that is especially warranted for patients antidepressant monotherapy is no more effective than mood stabilizers at treating taking antidepressants due to the risk GHA, WHE, SAC of manic switch. bipolar depression — and lacks maintenance properties. In fact, unopposed antidepressants may actually induce or worsen mania, promote rapid cycling between poles, and destabilize the course of bipolar treatment.EIMA, GYU, HSIN Despite this, antidepressants remain the most widely prescribed medications for the treatment of bipolar depression. Antidepressants should not be used without ADJUNCT MEDICATIONS mood-stabilizing medications to minimize a patient’s risk of switching to mania or rapid cycling, which further increases the risk of future switches. Benzodiazepines such as alprazolam, clonazepam, and lorazepam are often useful Bipolar II disorder (characterized by at least 1 depressive and 1 hypomanic episode for treating insomnia, anxiety, and agitation. over the course of a lifetime) lacks clear treatment guidelines; however, interventions Anticholinergics and beta-blockers are are critical for these patients for treatment and prevention, especially due to suicide used for patients at risk for or currently risk. Internationally, patients with bipolar II experience similarly high rates of suicidal experiencing medication-induced HSIN extrapyramidal symptoms (EPS) such as ideation (50.6%) and attempted suicide (20.8%) as those with bipolar I disorder. pseudo-Parkinsons, akathisia and acute A review of recent, evidence-based treatment strategies for bipolar II depression dystonia. Thyroid supplements may be necessary for some patients on lithium and bipolar depression with mixed features strongly recommends treatment with HSIN carbonate since it can interfere with thyroid quetiapine for acute therapy and lithium for maintenance therapy. functioning.

TABLE 5. Medications used to treat bipolar disorderKUP1,2; LEC1,2; LEX; POST; STA1,2; STO1,2 Medication Use (strength Dosage Tier/ Side effects and other comments Class (common brands) of evidence1) guidelines2 Cost3 (see page 16 for monitoring guidelines)

carbamazepine Mania (A), but Initiate: 1 •• Strong inducer of CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9, (Carbatrol, Tegretol) due to significant at 200 mg/twice and CYP3A4. $$ – $$$ side effects, use daily; then increase by •• Auto-inducer: Monitor and adjust serum levels due to liver only after trying all 200 mg/day at weekly induction. other meds with (A) intervals • Common side effects include dizziness, headache, nausea, strength evidence Range: • moderate weight gain, sedation and ataxia. Bipolar 400 – 1600 mg/day depression (C) Target: serum level •• Agranulocytosis, aplastic anemia, thrombocytopenia, hepatic failure Maintenance (B) 4 – 12 mcg/mL and toxic dermal eruptions can rarely occur. FDA-approved •• Prior to therapy, screen with HLA-B*1502 genotype.

valproate (or Mania and Initiate: 1 •• Common side effects include nausea, diarrhea, thrombocytopenia divalproex maintenance (A) at 25 mg/kg/day in and moderate weight gain. $$ – $$$ sodium) divided doses Bipolar •• Dose range presented is for valproate (divalproex). May be given (Depakote, depression Titrate: rapidly to as an extended release formula once daily instead; add 8 – 20% to Depakote ER) (B) (Better desired clinical effect total daily dose (usual 250 – 500 mg). at preventing Range: manic episodes •• Agranulocytosis, aplastic anemia, hyperammonemia, hepatic failure NOTE: divalproex 750 – 3,000 mg/day and toxic dermal eruptions can rarely occur. is referred to than depressive as valproate episodes) Target: serum level throughout this FDA-approved 50 – 125 mcg/mL (mid CPM. (for treatment of to upper range generally mania) required)

lsants lamotrigine Bipolar Initiate: 1 •• Do not titrate more rapidly than recommended dosing (Lamictal) depression, at 25 mg once daily schedule due to increased risk of potentially fatal rash. $ – $$ maintenance (A) Titrate: •• If taking with divalproex, halve titration doses; if taking with Mania (D); no per set schedule: carbamazepine, double titration doses (but no more than 100

Anticonvu acute efficacy for •• 25 mg once daily x 2 mg/day increase). mania wks •• Dose adjustment is needed if concomitant enzyme-inducing •• 50 mg once daily x 2 antiepileptic medication or valproic acid is discontinued. FDA-approved wks •• May provoke toxic dermal eruptions (Stevens-Johnson Syndrome, •• 100 mg once daily toxic epidermal necrolysis), but markedly reduced risk when titrated x 1 wk as directed; patient should seek medical attention immediately if a rash appears. •• 200 mg once daily thereafter •• Common side effects include nausea and rash; if continuing therapy despite rash, reduce dose and titrate more slowly once rash •• Further titrations <100 mg per day at resolves. weekly intervals •• Estrogen-containing oral contraceptives may decrease lamotrigine levels by 50%.

oxcarbazepine Mania, bipolar Initiate: 1 •• Strong inducer of CYP3A4. (Trileptal) depression, and at 300 mg twice daily; •• Common side effects include dizziness, headache, nausea and maintenance (C) $$ increase by 600 mg/day sedation. Not FDA- at weekly intervals • Agranulocytosis, aplastic anemia, hepatic failure, hyponatremia and approved Range: • toxic dermal eruptions can rarely occur. 600 – 2400 mg/day divided •• May reduce effectiveness of contraceptives Usual Target: •• Prior to therapy, screen for HLA-B*1502 genotype. 1,200 mg/day

1 Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usual- care experience; (D) = No acute efficacy 2 Some dosage guidelines are based on usual care experience and may differ from manufacturer’s package data. 3 Tier 1 = Generic; Tier 2 = Preferred Brand; Tier 3 = Non-Preferred Brand. Cost is based on 30-day actual cost (not copay), and on generic, when available: $=$1 – 25; $$=$26 – 75; $$$=$76 – 150; $$$$= > $1500

TABLE 5. Medications used to treat bipolar disorder (continued)KUP1,2; LEC1,2; LEX; POST; STA1,2; STO1,2 Medication Side effects and other comments Tier/ Class (common Use (strength of evidence1) Dosage guidelines2 (see Table 6A on page 16 for Cost3 brands) monitoring guidelines)

lithium Mania, maintenance (A) Initiate: 1 •• Effective for reducing suicide riskCIP carbonate at 300 mg twice daily; Bipolar depression (B) $–$$ •• May be given once daily as tolerated; (Eskalith, increase by ≤ 300 mg/day immediate release formulations generally Eskalith CR, Decreased efficacy in mixed every 3 – 4 days given in doses divided 2–3 times/day episodes, rapid cycling, and Lithobid) Range: comorbid substance abuse •• Multiple drug interactions (e.g., NSAIDs, 600 – 1500 mg/day ACEIs, diuretics) for treatment of FDA-approved Acute Mania Target: •• Moderate weight gain. acute mania and maintenance Serum level 1 – 1.5 mEq/L •• Common side effects include polydipsia, Maintenance Target: polyuria, acne, GI discomfort, hand tremor; 0.6 – 1.2 mEq/L most are serum-level related •• No significant sedation or stimulation Lithium Preparations

lithium 8 mEQ/5mL solution citrate

aripiprazole Mania, maintenance (A) Initiate: at 5 – 15 mg once 1 •• Common side effects include restlessness, (Abilify) daily stimulation, and nausea Bipolar depression (C) $$$$ Titrate: as tolerated to 30 •• Minimal risk of extrapyramidal symptoms (EPS) FDA-approved (for acute mg/day, if clinically indicated other than akathisia treatment of manic and mixed Range: 15 – 30 mg/day episodes associated with bipolar 1 disorder)

asenapine Mania (A) Monotherapy — 3 •• Sublingual administration only; no eating or drinking for 10 minutes after placing under (Saphris) Bipolar depression, Initiate: at 5 – 10 mg twice $$$$ tongue maintenance (B) daily by mouth •• Common side effects include headache, FDA-approved (for treatment dizziness and oral hypoesthesia of acute mania or mixed episodes Combination •• Minimal risk of EPS other than akathisia associated with bipolar 1 disorder as therapy — monotherapy or in combination with Initiate: at 5 mg twice daily •• Minimal sedation and little to no weight gain lithium or valproate) Titrate: to 10 mg twice daily

Atypical AntipsychoticsAtypical based on clinical response

lurasidone Mania, maintenance (C) Initiate: at 40 mg by mouth 3 •• Medication must be taken with food (at least once daily (increase as 350 calories) (Latuda) Bipolar depression (B) $$$$ clinically indicated) •• Common side effects include sedation, EPS, FDA-approved (for treatment of Range: 20 – 120 mg/day and nausea depressive episodes associated with bipolar 1 disorder as monotherapy •• Little to no weight gain or in combination with lithium or valproate)

1 Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usual- care experience; (D) = No acute efficacy 2 Some dosage guidelines are based on usual care experience and may differ from manufacturer’s package data. 3 Tier 1 = Generic; Tier 2 = Preferred Brand; Tier 3 = Non-Preferred Brand. Cost is based on 30-day actual cost (not copay), and on generic, when available: $=$1–25; $$=$26–75; $$$=$76–150; $$$$= > $1500 4 Strength of evidence is based on use as an adjunct to lithium or divalproex.

TABLE 5. Medications used to treat bipolar disorder (continued)KUP1,2; LEC1,2; LEX; POST; STA1,2; STO1,2 Side effects and other Medication Dosage Tier/ comments (see Table 6B Class (common Use (strength of evidence1) guidelines2 Cost3 on page 16 for monitoring brands) guideines)

olanzapine Mania, maintenance (A) Initiate: at 10 mg at 1 •• Significant sedation (Zyprexa, Zydis) bedtime Bipolar depression (B)4 $ – $$ •• Severe weight gain Titrate: by 5 mg • Medium risk of extrapyramidal symptoms FDA-approved (for treating bipolar 1 • increments at daily (EPS) disorder as follows): intervals •• Acute mania or mixed episodes as •• Potential for dyslipidemia and 5 – 20 mg at monotherapy or in combination with Range: hyperinsulinemia, case reports of diabetes risk bedtime (may be split lithium or valproate •• IM formulation effective for acute agitation •• Maintenance treatment twice daily)

olanzapine + •• Bipolar depression in combination with fluoxetine fluoxetine (Symbyax)

quetiapine Mania, bipolar depression, and Initiate: at 50 – 1 •• Significant sedation and moderate weight (Seroquel) 100 mg at bedtime gain; dry mouth maintenance (A) $ – $$$ • Lowest EPS risk of the atypical antipsychotics FDA-approved (for treating bipolar 1 Titrate: as clinically • disorder as follows): indicated •• Acute mania or mixed episodes as Range: 300 – monotherapy or in combination with 400 mg/day; up to lithium or valproate 800 mg/day may be • Maintenance treatment (in combination • needed with lithium or valproate) •• Acute treatment of depressive episodes May be given once (bipolar I and II disorder) nightly as tolerated

risperidone Mania (A) Range: 1 – 2 mg at 1 •• Moderate sedation and weight gain; (Risperidal) bedtime increases prolactin Bipolar depression (C) $ •• Minimal risk of EPS below 4 mg daily Maintenance (B) Titrate: by 1 mg Atypical Antipsychotics,Atypical continued increments at daily FDA-approved (for treatment of acute intervals mania or mixed episodes associated with Range: 1 – 6 mg at bipolar 1 disorder as monotherapy or in bedtime; may be split combination with lithium or valproate) to twice daily

ziprasidone Mania (A) Initiate: at 40 mg 1 •• Poor absorption without food; for best results (Geodon) twice daily with food take once daily with evening meal (minimum Bipolar depression (C) $$-$$$$ 500 calories) Titrate: to 60 – Maintenance (B)5 80 mg twice daily •• Minimal sedation at lower doses; little to no FDA-approved (for treatment of acute with food on day 2 weight gain •• Moderate risk of EPS manic or mixed episodes associated Range: 40 – 80 mg with bipolar disorder with or without twice daily with food •• Significant additional monitoring psychosis; for maintenance treatment requirements (see Table 6B on page 16) of bipolar disorder in combination with IM formulation effective for acute agitation lithium or valproate)

1 Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usual- care experience; (D) = No acute efficacy 2 Some dosage guidelines are based on usual care experience and may differ from manufacturer’s package data. In patients with repeated compliance issues, consider a long-acting injectable medication. 3 Tier 1 = Generic; Tier 2 = Preferred Brand; Tier 3 = Non-Preferred Brand. Cost is based on 30-day actual cost (not copay), and on generic, when available: $=$1 – 25; $$=$26 – 75; $$$=$76 – 150; $$$$= > $1500 4 Strength of evidence is based on use as an adjunct to lithium or divalproex. 5 Grade A evidence based on use in combination with fluoxetine

TABLE 6A. Monitoring Guidelines for Anticonvulsants and Lithium — Monitor (as clinically indicated) AND: KUP1,2; LEC1,2; LEX; POST; STA1,2; STO1,2 Anticonvulsants Test Lithium carbamazepine divalproex lamotrigine oxcarbazapine HLA-B*1502 genotype screening prior to screening prior to therapy1 FDA,CPIC therapy1 FDA CBC w/differential every 2 – 4 wks X 2 mos, at baseline; then 1 – 2 wks periodically at baseline and yearly then every 3 – 6 mos after any dose change Hepatic Function at baseline; then every at baseline; at baseline; then every 6 – 12 mos then yearly Renal Function 6 – 12 mos at baseline at baseline; every Thyroid Function 6 mos Pregnancy Test at baseline at baseline; at baseline then yearly Fasting Lipids Serum Sodium at baseline at baseline; then periodically during first 3 mos of therapy Serum Medication Level 3 – 4 wks after 1 – 2 wks after any dose 10 – 12 hrs after last (Trough) any sustained dose change dose, 4 – 5 days after adjustment initiation or dose change; then every 3 mos. Serum Ammonia when clinically indicated2 ECG at baseline and yearly Electrolytes at baseline Urinalysis at baseline

TABLE 6B. Monitoring Guidelines for Atypical Antipsychotics — Monitor (as clinically indicated)3 AND:ADA, GOT Pregnancy Test at baseline, if indicated (see page 17) Fasting Lipids at baseline; at 12 weeks; then annually BMI initial measurement; then at 4, 8, and 12 weeks; then every visit HgA1c/fasting plasma glucose at baseline; at 12 weeks; then annually Blood Pressure at baseline; at 12 weeks; then annually Extrapyramidal symptoms (EPS) baseline, then at each visit

1 In patients of Asian descent, DO NOT USE if the HLA-B*1501 allele is present. 2 For unexplained lethargy, vomiting, or mental status changes 3 For ziprasidone (Geodon), also do baseline ECG if known heart disease, personal history of syncope, family history of early sudden death or congenital long QT syndrome. Also monitor ECGs as clinically indicated for symptoms of prologed QT interval (e.g., syncope).

TABLE 7. Medication considerations for SPECIAL CIRCUMSTANCESHEN1-4; KUP1,2; LEC1; LEX; MAR; STA2

Circumstance Medication Considerations

Acute illness •• Lithium has been proven effective for reducing the risk of suicide in patients with acute illness.CIP •• Titrate medication dosage rapidly (except for lamotrigine — never rapidly titrate lamotrigine). •• Use respective adjunctive medications at beginning of treatment. •• Start co-therapy with two primary mood stabilizers from separate classes at beginning of treatment.

Akathisia •• Consider a cautious antipsychotic dose reduction •• Use lorazepam 0.5 mg twice daily (B); titrate as needed to manage symptom severity. •• Use propranolol 10 mg twice daily (C); gradually increase to 20 mg three times daily. Avoid in patients with asthma; watch for bradycardia and hypotension. •• Use benztropine 1 mg twice daily (C); increase to 2 mg twice daily as needed and tolerated.

Anxiety, •• Augment with a sedating atypical antipsychotic medication (see page 13), adjunctive sleeping pill, or sedative (benzodiazepine such agitation, and/ as clonazepam, lorazepam, alprazolam) 0.5 – 6 mg, in divided doses (A). or insomnia •• Suppression of manic symptoms, anxiety, or agitation with sedatives is a short-term solution. Avoid or use cautiously in patients with a history of substance abuse.

Bipolar II •• The hypomanic state of bipolar type II is often experienced as a functional and non-pathologic state. Aggressive treatment of this disorder state may lead to patient non-compliance. The consequences of not treating hypomania are unknown. •• Due to the possibility of lower manic conversion rates, antidepressant use may be less risky with this population compared to the bipolar type I population. However, antidepressants should be avoided in patients who are rapid cycling.

Elderly patient •• Consider half doses of medication. Older patients are more susceptible to lithium toxicity and suffer more side effects from medication. •• Monitor for increased suicide risk, more accidents, and self-neglect. •• Atypical antipsychotic medications may increase the risk of death in patients with dementia.

Female of •• Use anticonvulsant mood stabilizers with caution — many are generally regarded as teratogens. child-bearing •• For patients that plan to become pregnant, consider lamotrigine as first-line therapy (C). years •• Failing lamotrigine, consider quetiapine or risperidone as second-line therapies (C). Lurasidone may also be considered as second- line therapy. •• For treatment refractory patients, lithium is considered a reasonable option. While it is generally considered teratogenic (increased risk for cardiac defects), the absolute risk is low. •• Evaluate sexual activity, menstrual status, and birth control use at every visit for child-bearing age females on divalproex sodium, lithium, or carbamazepine.

Insomnia •• May be chronic in patients with bipolar disorder. Lack of adequate sleep may be both a sign of and a precipitant to relapse. •• Use adjunct sleeping medications. Benzodiazepine and related sedatives are helpful as sleep aids as well as for treatment (with mood stabilizer) of residual agitation and anxiety, though habit-forming sedatives should be avoided in patients with history of substance abuse. •• Educate patient on proper sleep hygiene: No evening caffeine or tobacco; no daytime napping; avoid reading and TV in bed; go to bed when sleepy; get out of bed if unable to fall asleep in less than 30 minutes.

Pregnancy Risk of relapse is high for those who discontinue mood stabilizers; near-term pregnant women are vulnerable to relapse.YON For patients with bipolar depression: •• Consider lamotrigine as first line therapy (C). •• Consider quetiapine as second-line therapy (C). Lurasidone may also be considered as second-line therapy. •• Treatment refractory patients are often treated with fluoxetine plus olanzapine, lamotrigine plus lithium, or electroconvulsive therapy (ECT). For patients with manic, hypomanic or mixed episodes: •• First-generation antipsychotics (e.g. haloperidol) are the preferred first-line therapy (B). •• Consider risperidone, quetiapine, or olanzapine (in that order) as second-line therapy (C). •• Treatment-refractory patients are often treated with lithium, electroconvulsive therapy (ECT), or lithium plus an antipsychotic.

TABLE 7. Medication considerations for SPECIAL CIRCUMSTANCES (continued)HEN1-4; KUP1,2; LEC1; LEX; MAR; STA2

Circumstance Medication Considerations

Rapid cycling For patients with bipolar depression: (four or more mood cycles •• Quetiapine is the preferred first-line therapy (C). per year) •• Consider lamotrigine, lithium, and fluoxetine plus olanzapine second-line agents, in order of preference (C). •• Failing the above, treatment refractory patients should be referred to a psychiatrist and potentially considered for electroconvulsive therapy (ECT), rather than additional pharmacotherapy trials (C). For patients with manic, hypomanic or mixed episodes: •• Consider risperidone, aripiprazole, or olanzapine monotherapy as first-line therapy (B). •• Second-line agents include lithium, valproate, quetiapine, haloperidol or carbamazepine, in order of preference (C). •• Failing the above, treatment refractory patients should be considered for combination therapy with either lithium or valproate and a first-line atypical antipsychotic. Alternately, in cases of severe mania, consider combination therapy a first-line option (C). •• For severe mania unresponsive to a single trial of combination pharmacotherapy, consider addition medication trials over electroconvulsive therapy (ECT). However, for severe mania unresponsive to 4 – 6 trials of combination pharmacotherapy, consider referral to a psychiatrist for electroconvulsive therapy (ECT) rather than additional pharmacotherapy trials (C). For all patients: •• Optimize thyroid function. •• Augment with psychotherapy.

Side effects intolerable •• Consider lower dose. prior to efficacy •• Change medications. •• Treat with low dose of two primary mood stabilizers.

Switch to opposite pole or •• Add mood stabilizer with efficacy for appropriate pole. mixed symptoms •• If depressed, raise lithium level to more than 0.8 mEq/L, add lamotrigine, quetiapine, OR add an antidepressant. Avoid TCAs, venlafaxine, and duloxetine. •• If manic or mixed, discontinue antidepressant (if that caused switch) or add a primary mood stabilizer for mania/ mixed mania. •• Patients who have a history of manic conversion on antidepressants are at high risk of future conversion with antidepressants.

Substance use disorder •• Avoid lithium as a primary mood stabilizer in these patients. •• Give appropriate referral and treatment for substance use issues. •• Use habit-forming sedatives with caution

Thyroid dysfunction •• Thyroid supplements may be necessary for some patients on lithium, since lithium carbonate can interfere with thyroid functioning. Consider treating subclinical hypothyroidism in patients who have resistant depression or rapid cycling.

Weight gain >5% of initial •• Modify treatment plan to include exercise and calorie restriction. weight or weight gain •• Follow weight, serum lipids, and fasting glucose. prevention •• Consider medication change — atypical antipsychotics may be associated with more weight gain than other mood stabilizing agents. •• Consider adjunctive use of metformin (B) or topiramate (B). Three small controlled studies showed diminished or reversed weight gain with metformin in patients who were taking atypical antipsychotics. One large trial showed an average three-year weight loss of 2.5% with metformin therapy, which was maintained over a 10-year observation period. A meta-analysis of six trials showed an average 6-month weight loss of 6.5% with topiramate therapy.

Worsening mania •• Assess medication adherence. •• Raise dose of existing mood-stabilizing medications AND/OR add second mood stabilizer for mania. •• Discontinue antidepressant if it is considered a precipitant. Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usual-care experience; (D) = No acute efficacy

Psychosocial therapy ADJUNCTIVE PSYCHOSOCIAL Patients with bipolar disorder suffer a variety of psychosocial consequences — THERAPY GOALS APA3,CAN,MIK stigmatization; interpersonal issues in marriage, family, childbearing, and parenting; Help patients better: academic, occupational, legal, and social problems — related to acute episodes • Understand and accept the nature of their (typically resulting from reckless and/or inappropriate behaviors or being withdrawn chronic illness and treatments or violent). The resultant stress of past episodes often sets these patients up for • Adhere to medication regimens ongoing vulnerability to future episodes. In addition, patients struggle to adhere to a • Recognize early warning signs of and long-term pharmacological treatment regimen with frequently unpleasant side effects. stressors that trigger relapse • Regulate their emotions and improve As a result, recent research-based clinical guidelines recommend that psychosocial functioning therapy be an essential part of a bipolar disorder treatment plan, especially for • Communicate and solve problems within APA3, CAN, VA maintenance treatment to: family relationships • Reduce stress • Regulate sleep/wake cycles and other • Increase patient functioning between episodes daily routines • Decrease likelihood and severity of future episodes • Avoid substance misuse Help family members/caregivers: Treatment strategies vary in terms of format (individual, group, or family unit), duration of treatment, patient cohort (in remission, recovering from an acute episode, • Increase illness management and their own self-care skills or both). As part of a treatment plan, therefore, psychosocial treatment strategies should be individualized over time for each patient in terms of form, intensity, and focus.APA3 • Decrease their own depressive symptoms • Decrease their health-risk behavior Evidence-based adjunctive psychosocial treatments for bipolar disorder include: • Individual cognitive-behavioral therapy (CBT) — Likely the most extensively researched modality as adjunctive therapy, CBT research reflects varying protocols and outcomes in comparison to other psychosocial treatments.MIK CBT is recommended for those in remission from acute mania who have experienced fewer than 12 previous acute episodes. With this treatment approach, patients learn about their symptoms, course of illness, and treatments as well as techniques for cognitive restructuring and problem-solving strategies for adapting activity levels to mood, detecting early signs of relapse, and implementing prevention strategies. Providers may want to consider booster sessions after 18 months to maintain treatment benefits.VA • Individual and/or group psychoeducation — This treatment approach focuses on helping patients become active partners in their treatment by learning: –– The nature and course of the illness –– Benefits/risks of treatment options –– How to recognize early signs and stressors that may signal relapse –– How sleep regulation and substance misuse impact likelihood of relapse Psychoeducation can involve the patient’s family members/caregivers if the patient agrees and providers should consider structured group psychoeducation, which has been validated in two randomized trials as effective for reducing the duration of patients’ manic episodes, lowering mania scores, and significantly improving patients’ social functioning and quality of life.MIK In addition, brief group psychoeducation has been found to be as effective as longer-term individual CBT at a significantly reduced cost (an 85% savings).PAR • Interpersonal and Social Rhythm Therapy (IPSRT) — This treatment approach addresses resolving patient-specific problems and focuses on stabilizing sleep/wake rhythms as well as patterns of social routines and stimulation. IPSRT uses a self- report tool, the Social Rhythm Metric, to track routines and mood. Designed for use with patients in remission, the treatment homes in on individualized problem resolutions and strategies for preventing problem recurrence. Some research indicates that IPSRT may be associated with longer time between episodes, better occupational functioning for those undergoing acute treatment, and even improved depression scores when used as monotherapy for those with bipolar II disorder.MIK

THE ROLE OF FUNCTIONAL • Family Focused Therapy (FFT) — Targeting couples and families of patients REMEDIATION stabilizing from acute episodes, this treatment approach includes both the patient and the family members and offers an initial assessment followed by education about: Those with bipolar disorder struggle with –– The illness, medication adherence, early warning signs of relapse, and relapse both social and occupational functioning prevention strategies — challenges that represent both clinical –– concerns as well as social and economic Communication and problem-solving skills to improve family relationships burdens. Functional remediation programs While patients whose families experience more conflict and intensity of relationships address struggles patients face with may benefit the most, research indicates that overall, patients involved in FFT attention, memory, and executive functioning as an adjunct to pharmacotherapy may experience a 35 – 40% reduction in in their daily routines. Elements of IPSRT (see recurrence rates over 2 years as compared to those undergoing brief psychoeducation page 19) also focus on functional remediation MIK by addressing stabilization of daily routines and pharmacotherapy. In addition, FFT can help caregivers increase illness and sleep/wake cycles. management skills as well as their own self-care, which is associated with decreased Adjunctive psychosocial interventions depressive symptoms and health-risk behavior among caregivers as well as decreased CAN focused on functional remediation have been depressive symptoms in patients. associated with significant improvements in occupational and interpersonal functioning Electroconvulsive therapy (ECT) among patients with both bipolar I and II With ECT, patients undergo a generalized cerebral seizure via administration of disorder. In a 2-year study of patients with bipolar I disorder, IPSRT combined with low-level electrical current to the scalp while under general anesthesia and muscle medical management rapidly improved relaxation. Treatment usually requires 6 – 12 sessions over a 2- to 4-week period. occupational functioning as compared to Although considered a standard treatment for unipolar depression, ECT has also other psychosocial approaches (especially among women), and these gains were been proven effective for acute mania, bipolar depression, mixed affective states, and LOO maintained for two years following the study. especially for treatment-resistant bipolar disorder. Other typical indications for FRA A multicenter, randomized controlled the use of ECT include multiple treatment failures, pregnancy, prior positive ECT trial of 239 euthymic patients with bipolar response, and patient preference. Studies also indicate that ECT may be effective as disorder compared functional remediation a first-line treatment to achieve rapid clinical response in urgent cases where patients with psychoeducation and treatment as usual present with severe suicidal ideation and behaviors, severe psychosis, malignant over 21 weeks. Results indicated significant APA4, HUS, improvements in both occupational and catatonia, or with dangerous, depression-related refusal of fluid and food. KEL1, KEL2 interpersonal functioning.TOR There are no absolute medical contraindications for using ECT; however, relative risk may differ depending on a patient’s clinical situation.APA4 Because of potential side effects, such as confusion and short-term memory loss (as well as side effects associated with anesthesia), ECT has typically been considered with treatment- resistant bipolar disorder patients. However, recent research indicates that these patients do not generally suffer adverse neurocognitive consequences and in fact, ECT may also be associated with a favorable long-term influence on some cognitive functions.KES, VER, BOD Care management With routine phone or clinic contact, care managers can educate patients regarding their care, set expectations, assist with social emergencies, and direct patients to return to the clinic sooner rather than later. Care managers offer both knowledge and a supportive relationship to patients — both of which are necessary for success. Patients who receive this type of care for depression have much better results than those who don’t. Working inside and outside the clinic, a care manager can assist with the following: • Treatment adherence (medications and/or psychotherapy) • Patient education, self-management, and reinforcement of ongoing physician, patient, and family contact • Communication and coordination between mental health and primary care • Support with requests for consultation • Improving timely contact with patients and monitoring their response

FOLLOW UP AND MAINTENANCE Since bipolar disorder is a chronic and reoccurring illness, it usually requires regular follow-up, lifetime maintenance pharmacotherapy, and ongoing, objective outcomes assessment. Sustained remission lowers relapse risk. Follow-up schedule Multimodal treatment of this complex disorder demands regular, lifelong follow-up. Objectives of follow-up include: • Adjusting medications and addressing side effects • Monitoring lab values (e.g., lithium serum levels) as indicated • Managing comorbidities • Continuing/coordinating therapy and education for patients and families • Measuring outcomes See below for a recommended follow-up schedule:

TABLE 8. Recommended follow-up schedule When Why THERAPEUTIC ALLIANCE 1 to 2 weeks after diagnosis and initial •• Assess initial response to treatment, assess medication therapy outcome. Clinicians should assess therapeutic alliance on a routine basis. Therapeutic alliance Every 4 weeks after diagnosis and initial •• Achieve target doses. refers to how well the patient and clinician medication therapy until patient is much improved •• Assess functional outcome (see page 18). are working together to manage the (CGI global improvement score 1 – 2). patient’s illness. The patient’s perception of •• Monitor side effects and adherence. this relationships is related to compliance • Assess educational needs. • and outcome. •• Assess therapeutic alliance (see sidebar). •• Assess for substance abuse (see page 8). Even limited alcohol use can destabilize the course of bipolar disorder.GOLD

At least every 6 months •• Monitor symptoms, lab values, and functional outcomes.

PRN •• Respond to worsening of symptoms or side effects, reinforce compliance. STICK WITH WHAT WORKS Remission and maintenance Whatever medication or medication regimens achieved remission of an acute episode Bipolar disorder is a recurrent illness. The goal of treatment is full, continuous should be continued without reduction of remission of symptoms. Nearly 3 in 4 patients will relapse within 5 years, and dosage as tolerated. many patients who do not have formal relapse will still exhibit significant residual The medications with the best symptoms. More than 90% of patients who experience one manic episode requiring empirical evidence (see medication details hospitalization will have a second episode. Patients hospitalized for mania are on pages 13 – 16) to support their more likely to have a mania relapse than a depressive relapse. Even with lifetime use in maintenance treatment include KUP1,2; LEC1,2; LEX; POS; STA1,2; STO1,2 maintenance therapy, patients may experience only partial remission of symptoms.TOH the following: • Lithium, valproate, olanzapine, and Due to the recurrent nature of bipolar disorder—and high probability of relapse— aripiprazole (better at preventing lifetime maintenance regimens of medication are recommended following the manic relapse) successful treatment of an acute episode. Although few studies involving patients with • Quetiapine when used in combination with bipolar II disorder have been conducted, consideration of maintenance treatment for lithium and valproate this form of the illness is also strongly warranted. One long-term follow-up study • Ziprasidone when used in combination with showed that patients with bipolar II disorder have chronic depressive symptoms more fluoxetine JUD1, JUD2 than half of the time. • Lamotrigine (better at preventing depressive relapse)

BE CONSISTENT Outcomes assessment tools Measure treatment Traditionally, symptomatic outcome measures — such as the Young Mania Rating outcomes in a consistent, Scale or the Hamilton Depression Rating Scale — have been used in bipolar disorder. comprehensive, and efficient These measures focus specifically on the core disease symptoms and are useful in way, using the tools described research. However, bipolar disorder is a highly comorbid condition; over half of patients on these two pages. also suffer anxiety disorder and substance abuse disorders throughout their lifetime. Medication side effects can also add a significant burden. For these and other reasons, basic symptom measures do not adequately track these issues and often miss significant functional impairment important to both patients and clinicians. To address shortcomings in traditional outcomes measurement, this CPM recommends two essential types of clinical measures: • The clinician-rated Clinical Global Impressions (CGI) Scale for treatment responseGUY • The patient-rated Intermountain Disability Scale for functional response In addition to these clinical measures, having selected patients use a daily mood chart (see page 23) to track function impairment is also useful.

GUY ASSESS SEVERITY The Clinical Global Impressions (CGI) Scale ROUTINELY Requiring only 5 minutes or less to complete, the Clinical Global Impressions (CGI) Scale is a simple, valid measure of treatment response. In its simplest form, the clinician rates Rate and record the severity a patient’s severity of illness and response to treatment. This scale tracks well with score at the initial visit and at symptom scales, and clinicians often closely agree with each other when scoring the same all subsequent visits. patient. To use the CGI Scale, rate the severity of illness at the initial visit and all subsequent visits. Based on your experience with this disorder, use the 1 – 7 scale below. Severely ill patients routinely suffer comorbid illness; incorporate this factor into the rating.

Severity scale 1 – 7: 1 2 3 4 5 6 7 normal, borderline mildly moderately markedly severely extremely not ill ill ill ill ill ill ill

The Intermountain Disability Scale Intermountain’s functional disability rating scale (on the next page) can be downloaded at: https://intermountainhealthcare org/ext/Dcmnt?ncid=526842760. Instruct the patient to rate their level of disability by asking, “In the past 2 weeks, how much have your mental health symptoms interfered in the following areas of life?” Patients should rate each of the three domains (family life and home responsibilities, work or school, and social or leisure activities), providing a total functional disability score from 0 – 30.

Intermountain Disability Scale Access the Intermountain Disability Scale at: https://intermountainhealthcare org/. ext/Dcmnt?ncid=526842760

Daily mood charting RATE IMPAIRMENT DAILY Daily mood charting provides a way for patients to rate impairment caused by Instruct the patient to use this depressive or manic systems in relation to daily medications, interpersonal stress, chart every day to rate impairment sleep, and other variables. Use of a mood chart is widely recommended for patients caused by symptoms, medications, with rapid cycling, particularly those who have mood cycling within a single month. stress, sleep, and other variables. Recording a mood along with any medications taken, medication changes, or other events can provide evidence for which interventions are helpful or destabilizing.

Daily Mood Tracking Chart

Directions: At the end of each day, use this calendar to record your medications, overall mood, hours of sleep, and other symptoms and/or life events. This will help you and your healthcare provider monitor and improve your treatment.

Patient name: Month: Year:

DATES

1. CHART YOUR MEDS (record number of pills each day) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Name of medication Pill strength # pills/day

Access this mood tracking chart under the “bipolar 2. CHART YOUR MOOD ( your mood each day and how it 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 disorder” topic at: has affected your ability to function at work, home, or school) intermountainphysician.org/ 4 Severe: Completely unable to function or hospitalized clinicalprograms 3 Moderate to High: Great difficulty functioning 2 Moderate: Some difficulty functioning Mania 1 Mild: Usual routine not affected much; may be more active than usual 0 Stable mood: no mania or depression 1 Mild: Usual routine not affected much; depressed mood 2 Moderate: Some difficulty functioning 3 Moderate to high: Great difficulty functioning

Depression 4 Severe: Completely unable to function or hospitalized

3. RECORD OTHER HABITS AND EVENTS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

# hours slept last night

Used alcohol or drugs ( if yes – or enter number of drinks) Other symptoms or life events ( if yes; date and describe on back) Example symptoms: pain, taking risks, feeling paranoid or irritable Example life events: argument, promotion, family conflict

TOOLS USED FOR SCREENING BIPOLAR DISORDER IN CHILDREN AND AND DIAGNOSIS ADOLESCENTS Although there is disagreement within the specialty of child psychiatry regarding Many emotional and behavioral illnesses of childhood have symptoms that converge bipolar diagnoses, there are reasonable and confuse the identification and appropriate treatment of bipolar disorder in guidelines and tools for diagnosing children and adolescents. Presentation of symptoms often differs from that in adults, childhood and adolescent bipolar disorder. and children tend to have higher rates of chronicity, mixed states, and rapid cycling. However, it is critical that the care provider use the symptom expression information A reliable diagnosis of bipolar disorder in the pediatric population depends at right and not rely solely on screening on symptoms: instruments. Validated tools include: • Occurring in concert rather than sequentially • The MDQ-A (Mood Disorder Questionnaire-Adolescent). • Being considered in the context of age and comorbidity This screening instrument has been validated in adolescents, with the parent The diagnosis of cyclothymic disorder in children and adolescents is one year of report version having the greatest both hypomanic and depressive episodes without ever meeting criteria for mania, sensitivity and specificity.WAG depression, or hypomania, while the requirement for adults is 2 years. • The Young Mania Rating Scale. This scale was developed to rate acute mania severity but also functions as a Symptom expression screening instrument when rated by a Symptom expression of bipolar disorder in children and adolescents differs from that parent. The P-YMRS is the parent-rated version of this scale.GRA of adults and is influenced by developmental changes, temperament, and reaction to environmental stress. Distinct periods of depression and mania are less likely • FIND guidelines. Childhood bipolar disorder may present with symptoms in younger populations, and these patients may present with chronic symptoms of that are frequent, brief, and intense with irritability, along with difficulties regulating moods, emotions, and behavior. Younger outbursts and behavioral dysregulation children may also have periods of agitation, irritability, and oppositionality as generic fundamentally different from the adult presentation of the illness. The FIND symptoms of any severe mental illness. guidelines below include duration and Mania in adolescents presents many diagnostic challenges based on historical intensity criteria, and are recommended by many researchers to ascertain the presence reporting. Both adolescents and their parents may either minimize symptoms of or absence of manic symptoms.KOW mania (to downplay the seriousness of the situation) or exaggerate these symptoms (hoping that a bipolar disorder diagnosis will explain the difficulties the patient is experiencing). Symptoms that typically present include: FIND GUIDELINES FOR PEDIATRIC PATIENTSKOW • Grandiosity: Determine the child’s ability to distinguish between pretending and These guidelines can help clinicians reality to establish if grandiose symptoms are due to bipolar disorder. ascertain the presence or absence of manic • Euphoria/Irritability: Review these moods in the context of special events, the symptoms: behavior of other children, and exposure to steroids or substance abuse. Irritability that results in major “meltdowns” lasting hours for trivial reasons should be F Frequency. Symptoms occur separated from less severe irritable moods. most days of the week. • Decreased need for sleep: A child with bipolar disorder may need 2 hours less I Intensity. Symptoms are sleep per night (adjusted for age without daytime fatigue). Children with limited severe enough to cause extreme sleep due to mania are often active during the night whereas depressed children disturbance in 1 domain or may lie in bed and brood. moderate disturbance in 2 or more domains (school, home, • Pressured speech: Speech is louder, faster, and more difficult to interrupt than a friends, etc.) child with ADHD who talks a lot.

N Number. Symptoms occur 3 or • Mood lability: For adolescents, mood lability may be the way mania presents. 4 times per day. In fact, it is not unusual for patients to experience mixed manic and depressive features of a mood disorder, a more common symptom picture than the persistent D Duration. Symptoms occur euphoria found in adults. 4 or more hours a day total (not necessarily contiguous hours)

• Racing thoughts: These thoughts should be severe enough to interfere with daily THE IMPORTANCE OF activities. Parents can help distinguish what behaviors are different than baseline. REFERRAL • Distractibility: Compare distractibility to baseline symptoms when mood is Bipolar disorder is relatively rare in euthymic. Symptoms in children with comorbid ADHD should have distractibility children and complicated to diagnose. worse than baseline distractibility. In terms of mania, “Bipolar ‘mood episodes’ include unusual mood • Increase in goal-directed activity/agitation: Mania may be associated with changes along with unusual sleep periods of copious drawing, writing, or play activities. This should be above and habits, activity levels, thoughts, or behavior. In a child, these mood and beyond normal and associated with other diagnostic symptoms. activity changes must be very different • Excessive Involvement in Pleasurable or Risky Activities: Hypersexual from their usual behavior and from the NIH behaviors may be present in children with or without a history of childhood behavior of other children.” Highly irritable children are more likely to abuse. This behavior may be exhibited in an anxious and compulsive manner. have ADHD or an anxiety or depressive Hypersexuality in children due to mania can appear as erotic and pleasure-seeking disorder. behaviors that might be appropriate between consenting adults in private but grossly inappropriate in a child. Sexual and/or seductive advances towards a parent Red flag symptoms for diagnosing mania in this patient population include:SHA would not be unusual. • Psychosis: It is important to differentiate hallucinations or delusions from • Rage outbursts or verbal or physical aggression — The patient common childhood perceptual disturbances such as hearing one’s name called or may be easily frustrated or provoked. other distortions when falling asleep. Symptoms of psychosis frequently occur in • Episodes of requiring little sleep adolescents experience bipolar disorder. — The patient gets less sleep frequently without suffering any loss of energy. Differential diagnosis and comorbidity • Spontaneous mood shifts — The patient may be giddy, then depressed, One of the biggest challenges is differentiating children and adolescents with mania then angry without any apparent trigger from those with attention deficit hyperactivity disorder (ADHD). These patients for the mood shifts. should also be screened for other problems such as learning problems, substance use, • Grandiosity – The patient may exhibit and conduct disorders — and those problems should be treated concurrently. a grossly inflated belief in himself beyond typical boastfulness. There are high rates of comorbid disruptive, impulse-control, and conduct disorders • Agitation or mania when taking that accompany the bipolar diagnosis. Additionally, in disruptive mood dysregulation an antidepressant — The patient disorder (a depressive disorder), children present with irritability as the chief may have had symptoms of being complaint. Temper outbursts occur on average more than 3 times per week, but unusually edgy, happy when taking an the moods in between the outbursts are “persistently irritable” unlike with bipolar antidepressant. disorder where there is often some cycling nature. Given the uncertainty and potential complications in diagnosing and treating KOW bipolar disorder in this population, Treatment guidelines consultation with or referral to a Treatment of bipolar disorder in young patients generally reflects that of adult child mental health specialist is patients — and should include patient/family education, psychotherapy, and recommended before initiating pharmacotherapy. Young patients experiencing bipolar symptoms can benefit from treatment. psychosocial interventions (see pages 19 – 20). In addition, patients may require specialized educational programming, day treatment, and vocational training. The literature on the use of ECT (see page 20) in pediatric bipolar patients is extremely limited, and the treatment should only be considered for adolescent patients suffering from bipolar I disorder with severe symptoms of mania or depression that are unresponsive to multiple medication therapies.

FDA-APPROVED MEDICATIONS Medications The following medications are approved The choice of the medications used to treat pediatric bipolar disorder should be based for treating bipolar disorder in children on evidence of efficacy, the phase of illness (manic versus depressive symptoms), the and adolescents as indicated: drug’s side-effect profile, the patient’s history of medication response, and patient and • lithium carbonate (Eskalith, Eskalith CR, family preferences. Lithobid) — Approved for ages >12 years as monotherapy for acute mania and Prescribing guidelines emphasis a stepwise nature of medication management as well as maintenance rationale for combining medications. At each step in pharmacotherapy, the physician is • aripiprazole (Abilify) — Approved for balancing the benefits and risks of either staying with a current regimen (if the patient ages >10 years (as monotherapy or in appears to be stable or improving) or changing medications or doses to optimize combination with lithium or valproate (or treatment. This process should be very patient-specific, with the following key issues divalproex) for acute mania guiding decision making at each step:SHAI • asenipine (Saphris) — Approved for ages >10 years as monotherapy for acute mania/ • Making only one medication change at a time mixed episodes • Addressing the most problematic symptom or cluster of symptoms first • olanzapine (Zyprexa, Zydis) — Approved for ages >13 years as monotherapy for • Reducing the number of medications that will eventually be needed acute mania/mixed mania and maintenance • • olanzapine (Zyprexa, Zydis) in Making management of adverse effects a priority when warranted combination with fluoxetine • Targeting symptoms that appear to trigger other symptoms (Prozac) — Approved for ages 10–17 for treatment of bipolar depression • Preferring medications that work quickly • quetiapine (Seroquel) — Approved Both the range of symptoms present with bipolar disorder and the symptoms that for ages >10 years as adjunct and monotherapy for acute mania occur as a result of comorbidities often make medication management particularly • risperidone (Risperidol) — approved for challenging for children and adolescents. Combining medications is often SHAI ages >10 years (as monotherapy for acute appropriate when: mania/mixed episodes • Using an augmentation agent to address only partial response when symptoms either improve but not to a degree that lessens significant distress or when symptoms fail to improve at all • Targeting a specific symptom that causes significant distress such as insomnia • Cross-tapering medication that is not working as expected with another medication • Treating symptoms of comorbid disorders such as those with ADHD or anxiety disorder Use the dosage guidelines in the medication table (page 27) for treating children and adolescents. For each medication, refer to the adult medication tables on pages 13 through 15 for tier/cost and side effect information that pertain to all populations. Dosages must be modified for age, and response to treatment must be carefully monitored. Side effects — particularly weight gain — may be exaggerated in children, CARE MANAGEMENT and children are more prone to medication toxicity. The follow-up and maintenance care Maintenance and medication monitoring of children and adolescents as well as Patients are likely to require maintenance therapy to prevent symptom relapse with outcomes assessment tools used follow a recommended trial of 12 to 24 months after an acute manic episode. Decisions to the same processes as detailed for adults continue treatment must be weighed along with risks of medication side effects. on pages xx through xx. Note that, for a younger child, a parent or other caregiver Recommended medication monitoring for children and adolescents is the same as for would be completing the forms. adults (see Tables 6A and 6B on page 16).

TABLE 9. Medications for treating children and adolescentsELB, LEC2, LEX, STA1, STA2

Class Medication Strength of Dosage guidelines2/Notes (see pages 13 – 16 for specific medication side effects (common Evidence1 and monitoring guidelines) brands) divalproex Mania, bipolar Children: Adolescents: sodium depression, and •• Initiate at 125 mg 2 – 3 times daily •• Initiate at 250 mg 2 – 3 times daily (Depakote, maintenance (C) •• Increase gradually until side effects limit dose or •• Increase gradually until side effects limit dose Depakote ER) therapeutic plasma levels are reached or therapeutic plasma levels are reached Not FDA •• Range: 1000 – 1250 mg/day •• Range: 1000 – 2500 mg/day approved for •• Target: Serum level 50 – 125 mcg/mL (mid to upper range generally required)

Anticonvulsants this population

lithium Mania, bipolar Ages 6 – 12 years: Ages ≥ 12 years: carbonate depression (C) •• Initiate at 15 mg/kg/day in 3 – 4 divided doses •• Initiate at 300 mg twice daily (Eskalith, maintenance (B) •• Adjust dose weekly based on serum concentrations •• Increase by ≤ 300 mg per day every 3 – 4 days Eskalith CR, •• Range: 15 – 60 mg/kg/day (do not exceed adult dosage) •• Range: 600 – 1800 mg/day

antimanic Lithobid) •• Target: Serum level 0.8 – 1.2 mEq/L Metallic salt,Metallic

aripiprazole Mania, Ages ≥ 10 years: (Abilify) maintenance (B), •• Initiate at 2 mg once daily x 2 days bipolar •• Increase to 5 mg PO once daily x 2 days, then may increase in 5 mg increments depression (C) •• Range: 10 – 30 mg/day asenapine Mania, Ages ≥ 10 years (Note: Sublingual administration only; no eating/drinking for 10 minutes after placing under (Saphris) maintenance (B), tongue): bipolar •• Initiate at 2.5 mg twice daily depression (C) •• Increase to 5 mg twice daily after 3 days, then to 10 mg twice daily in another 3 days based on tolerability olanzapine3 Mania, Ages 6 – 12 years: Ages ≥ 12 years: (Zyprexa, Zydis) maintenance (B) •• Initiate at 2.5 mg at bedtime •• Initiate at 2.5 – 5 mg at bedtime Increase in bipolar •• Increase in 2.5 – 5 mg increments 2.5 – 5 mg increments weekly depression (B)4 •• Range: 10 – 20 mg/day •• Range: 10 – 20 mg/day combined Bipolar depression: Ages 6 – 10 years: Ages 10 – 17 years: with ages 10 – 17 (C), •• Initiate at 5 mg •• Initiate at 10 mg ages 6 – 10 (D) fluoxetine •• Increase as clinically indicated •• Increase as clinically indicated (Prozac, Symbyax) quetiapine Mania, Ages ≥ 10 years (Note: May be given once nightly if tolerated): (Seroquel) maintenance (B) •• Initiate at 25 mg twice daily Atypical AntipsychoticsAtypical bipolar •• Increase to 50 mg twice daily on day 2, then 100 mg twice daily on day 3, 150 mg twice daily on day 4, and depression (C) 200 mg twice daily on day 5. •• Range: 400 – 600 mg/day in divided doses risperidone Mania, Ages ≥ 10 years: (Risperidal) maintenance (B) •• Initiate at 0.5 mg at bedtime bipolar •• Titrate by 0.5 – 1 mg increments at daily intervals, as tolerated depression (C) •• Range: 0.5 – 2.5 mg at bedtime (may be split twice daily) ziprasidone Mania (B) Ages ≥ 10 years: (Geodon) bipolar depression, •• Initiate at 20 mg once daily with food Not FDA- maintenance (C) •• Titrate as tolerated approved for this •• Range: 60 – 80 mg/day divided twice daily population5 (weight ≤ 45 kg) or 120 – 160 mg/day divided twice daily (weight > 45 kg)

1 Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usual-care experience; (D) = No acute efficacy. NOTE: See FDA-approved medication information for this population in the sidebar on page 26. 2 Some dosage guidelines are based on usual care experience and may differ from manufacturer’s package data. 3 Zyprexa is ONLY FDA-approved for treatment of acute bipolar depression for ages 10 – 17 in combination with fluoxetine and for treatment of acute manic or mixed episodes for ages 13 – 17. 4 Strength of evidence is based on use as an adjunct to lithium or divalproex. 5 While an FDA advisory panel has advised that ziprasidone is effective in patients 10 – 17 years of age for the treatment of mixed and manic episodes of bipolar disorder, they were unable to conclude that it was safe due to the large number of subjects lost to follow-up and ambiguity within QTc prolongation data

USING TEACH-BACK STRATEGIES PATIENT/FAMILY EDUCATION What is Teach-back? — Teach-back is a way to confirm that patients understand what Patient and family education can lead to better compliance and treatment outcomes. we tell them using open-ended questions that Review the available patient education materials (see page 29) and resources for using invite the patient and family to “teach-back” teach-back strategies (see the information at left and the Teach-back Flashcard). the information to us. It’s not a test of the patient’s knowledge — it’s a test of how well In addition to basic information about the symptoms, neurobiologic basis, and treatment we explained something. of the disease, patient education should include the following topics: Why is it important? — Not • Warning symptoms and prodromal symptoms. Symptoms may arise weeks or understanding medical information is a months prior to a full-blown episode. Often, these symptoms are the same before common reason for readmissions. Teach- back is a proven tool for improving patient each episode for an individual patient and are likely to include changes in sleep, understanding. activity level, and impulsivity.FAV, SMI Help patients recognize these symptoms Who can use it? — Everyone who and act to prevent relapse. Patients who develop strategies to handle prodromal explains anything to a patient or family. symptoms are less likely to relapse.LAM Educate family members about prodromal When can I use it? — Use early in the symptoms; they often notice these changes before the patient is aware of them. care process and at each decision point • The effects of substance use and abuse. Alcohol and illegal drug use can or transition, especially when families or caregivers are present. Make sure caregivers lead to more frequent relapse, poor response to lithium, and a more severe course participate in the Teach-back process to of illness. Even limited use of alcohol or marijuana can destabilize this illness. ensure they understand key information. Educate patients who use or abuse substances on how and where to get help. What are the Steps? • The importance of treatment adherence. Treatment adherence is improved by 1. Explain or demonstrate a concept, using a better understanding of this illness, its course, and likelihood of relapse. During simple lay language. times of normal mood or hypomania, patients may not perceive themselves as Tips: Avoid covering too much at one time — explain no more than 2 or 3 being sick or needing treatment. Encourage patients to stick to the medication concepts at a time. Slow down and take schedule even when they are feeling well. Medication side effects may also lead to pauses. If you’re giving the patient printed poor treatment adherence. Teach patients to recognize and report side effects so information, mark or highlight key areas of medications can be adjusted. the handout or booklet as you explain. 2. Ask the patient/caregiver to repeat • The role of stress. Patients who understand the link between stress and symptom the information in their own words or recurrence and then learn strategies for coping with stressful events may be able demonstrate the process. to reduce the impact stress has on the onset of mania and depression. Research Tips: Own the responsibility (“I want to see whether I explained this well”). Ask indicates that many patients with bipolar disorder suffer from recurring symptoms JOH the patient to tell you how he or she would after stressful life events that affect one’s ability to attain goals. Additionally, explain the information to a spouse or there is an association between recurrent episode onset and patients who have family member. Avoid yes/no questions. experienced childhood physical, sexual, or emotional abuse.GIL 3. Identify and correct misunderstandings. • Tips: Show empathy and caring as you The connection between sleep and episode severity. It is important to help correct. Avoid making the patient feel patients understand that the amount of sleep they get and the regularity of their they’ve failed a “test.” Don’t repeat the sleep patterns translates to less severe symptoms of both mania and depression. entire explanation or demonstration again Results from a study of concurrent and prospective associations from the National unless it’s necessary — just focus on areas that need clarification. Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial indicated an association between shorter total 4. Ask the patient/caregiver to explain or demonstrate again, to show improved sleep time and increased mania severity as well as an association between greater understanding. sleep variability and increased mania and depression severity over 12 months.GRU Tips: Own the process again. “Let’s see if I cleared that up.” Avoid yes/no questions (such as “do you understand now?”). 5. Continue this loop until you’re convinced the patient/caregiver understands the concept. Tips: Be patient — this process is worth the time it takes. Continue to be gracious in the process — patients can worry about judgment or wasting your time.

RESOURCES AND REFERENCES Intermountain patient resources Clinicians can order Intermountain patient education booklets and fact sheets for distribution to their patients from Intermountain’s Online Library and Print Store, iprintstore org. . Call 801-442-3186 for ordering information. Choose from an array of booklets, trackers, and forms to Mental Health Integration Adult

Mood Disorder Questionnaire (MDQ) (page 1 of 1) help, including: Today’s Date: Patient’s Name: Date of Birth: YES NO 1 Has there ever been a period of time when you were not your usual self and…

… you felt so good or so hyper that other people thought you were not your normal self,

or you were so hyper that you got into trouble? Daily Mood Tracking Chart

… you were so irritable that you shouted at people or started fights or arguments? Directions: At the end of each day, use this calendar to record your medications, overall mood, hours of sleep, and other symptoms and/or life events. This will help you and your healthcare provider monitor and improve your treatment. … you felt much more self-confident than usual? • Adult Bipolar Disorder Information for Patients and families Month: Year: DATES … you got much less sleep than usual and found you didn’t really miss it? Mental Health Integration 1. CHART YOUR MEDS (record number of pills each day) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Patient Health Questionnaire (PHQ-9) (page 1 of 1) … you were much more talkative or spoke much faster than usual? Name of medication Pill strength # pills/day

… thoughts raced through your head or you couldn’tToday’s slow Date: your mind down? Patient’s Name: Date of Birth:

… you were so easily distracted by things aroundAre you you that currently: you had trouble on medication concentrating for depression?  not on medication for depression?  not sure?  in counseling?

or staying on track? Over the last 2 weeks, how often have you been bothered by any of the Several More than Nearly every • Not at all PHQ-9 … you had much more energy than usual? following problems? days half the days day

… you were much more active or did many more1. things Little than interest usual? or pleasure in doing things 0 1 2 3 2. CHART YOUR MOOD ( your mood each day and how it … you were much more social or outgoing than usual; for example, you telephoned friends 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 2. Feeling down, depressed, or hopeless 0 1 2 3 has affected your ability to function at work, home, or school) in the middle of the night? 4 Severe: Completely unable to function or hospitalized … you were much more interested in sex than usual?3. Trouble falling/staying asleep, sleeping too much 0 1 2 3 3 Moderate to High: Great difficulty functioning

Mania 2 Moderate: Some difficulty functioning … you did things that were unusual for you or that other people might have thought were • 4. Feeling tired or having little energy 0 1 2 3 1 Mild: Usual routine not affected much; may be more active than usual MDQ excessive, foolish, or risky? 0 Stable mood: no mania or depression 5. Poor appetite or overeating 0 1 2 3 … spending money got you or your family into trouble? 1 Mild: Usual routine not affected much; depressed mood 2 Moderate: Some difficulty functioning 6. Feeling bad about yourself — or that you’re a failure or have let 2 If you checked YES to more than one of the above, have several of these ever happened during 0 1 2 3 3 Moderate to high: Great difficulty functioning yourself or your family down the same period of time? Depression 4 Severe: Completely unable to function or hospitalized 7. Trouble concentrating on things, such as reading the newspaper 0 1 2 3 3 During the period of time indicated above, do you thinkor any watching of these television symptoms were brought on 3. RECORD OTHER HABITS AND EVENTS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

by prescription or other drugs? • 8. Moving or speaking so slowly that other people could have noticed, # hours slept last night Daily Mood Tracking Chart or the opposite — being so fidgety or restless that you have been 0 1 2 3 4 How much of a problem did any of these cause you — like being unable to work; having family, money, or legal troubles; or Used alcohol or drugs ( if yes – or enter number of drinks) getting into arguments or fights? moving around a lot more than usual Other symptoms or life events ( if yes; date and describe on back) 9. Thoughts that you would be better off dead or of hurting yourself Example symptoms: pain, paranoia, risky behaviors 0 1 2 3 no problem minor problem in moderate some way problem serious problem Example life events: argument, promotion, family conflict

Total each column Name: Patient For Office Use Only: © 2007 Intermountain Healthcare. All rights reserved. Clinical Education Services 801.442.2963 IHCEDMH200 - 3/08 *50179* How difficult have these problems made it for you to do your work, /take 13 care of things at home, or get along with other people? Trc 50179 Reprinted with permission from the American Journal of Psychiatry, (Copyright 2000). American Psychiatric Association. A.  Not difficult*50402* at all  Somewhat difficult  Very difficult  Extremely difficult ©2004–2014 Intermountain Healthcare. All rights reserved. MHI Pack 50402 Patient and Provider Publications 801-442-2963 MHI019 - 10/14 B. In the past 2 years, have you felt depressed or sad most days, even if you felt okay sometimes?  YES  NO

Comments: For Office Use Only: Symptom score (total # of answers in shaded areas): Severity score (total all points from all questions):

*50408* PHQ 50408 The PHQ-9, copyright ©1999 by Pfizer Inc., is now in the public domain. PRIME-MD® and PRIME MD TODAY® are trademarks of Pfizer Inc. ©2004–2014 Intermountain Healthcare. All rights reserved. Patient and Provider Publications 801-442-2963 DEP601 - 10/14

Provider resources To find this CPM, clinicians can go tointermountain .net/clinical/Pages/All-Care-Process-Models-(CPMs) .aspx, and select “Behavioral Health” from the topic list on the screen (as indicated below).

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SAR Sareen J, Cox B, Afifi T, et al. Anxiety disorders and risk for suicidal ideation SUP2 Suppes T, Mintz J, McElroy SL, et al. Mixed hypomania in 908 patients with and suicide attempts: a population-based longitudinal study of adults. Arch bipolar disorder evaluated prospectively in the Stanley Foundation Bipolar Gen Psychiatry. 2005;62(11):1249-1257. Treatment Network: a sex-specific phenomenon. Arch Gen Psychiatry. SCHI Schiffer RB, Wineman NM, Weitkamp LR. Association between bipolar 2005;62(10):1089-1096. affective disorder and multiple sclerosis. Am J Psychiatry. 1986;143(1):94-95. TOH Tohen M, Zarate CA Jr, Hennen J, et al. The McLean-Harvard First-Episode SCHN Schneck CD, Miklowitz DJ, Calabrese JR, et al. Phenomenology of rapid- Mania Study: prediction of recovery and first recurrence.Am J Psychiatry. cycling bipolar disorder: data from the first 500 participants in the Systematic 2003;160(12):2099-2107. Treatment Enhancement Program. Am J Psychiatry. 2004;161(10):1902-1908. TOR Torrent C, Bonnin Cdel M, Martinez-Arán A, et al. Efficacy of functional SHA Shah NN, Averill PM, Shack A. Mixed versus manic bipolar disorder: a remediation in bipolar disorder: a multicenter randomized controlled study. comparison of demographic, symptomatic, and treatment differences. Am J Psychiatry. 2013;170(8):852-859. Psychiatr Q. 2004;75(2):183-196. VA Department of Defense, Department of Veterans Affairs. VA/DoD SHAI Shain BN; Committee on Adolescence. Clinical report: Collaborative role Clinical Practice Guideline for Management of Bipolar Disorder in Adults. of the pediatrician in the diagnosis and management of bipolar disorder in Washington, DC: Department of Defense, 2010. 43-58. adolescents. Pediatrics. 2012;130(6):e1723-e1742. VER Versiani M, Cheniaux E, Landeira-Fernandez J. Efficacy and safety of SMI Smith JA, Tarrier N. Prodromal symptoms in manic depressive electroconvulsive therapy in the treatment of bipolar disorder: a systematic psychosis. Soc Psychiatry Psychiatr Epidemiol. 1992;27(5):245-248. review. J ECT. 2011;27(2):153-164. doi: 10.1097/YCT.0b013e3181e6332e. STA1 Stahl SM. Prescriber’s Guide: Stahl’s Essential Psychopharmacology (5th ed). WAG Wagner KD, Hirschfeld RM, Emslie GJ, Findling RL, Gracious BL, Reed ML. New York, NY: Cambridge University Press; 2014. Validation of the Mood Disorder Questionnaire for bipolar disorders in adolescents. J Clin Psychiatry. 2006;67(5):827-830. STA2 Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4th ed). New York, NY: Cambridge University Press; WEE Weeke A, Juel K, Vaeth M. Cardiovascular death and manic-depressive 2013. psychosis. J Affect Disord. 1987;13(3):287-292. STO1 Stovall J. Bipolar disorder in adults: pharmacotherapy for acute mania and WEI Weissman MM, Johnson J. Drug use and abuse in five US communities. hypomania. In: UpToDate, Keck P (Ed), UpToDate, Waltham, MA. Updated N Y State J Med. 1991;91(11 Supp):19S-23S. March 14, 2016. Accessed on April 13, 2016. WHE Wher TA, Deal S. Rapid cycling affective disorder: contributing factors and STO2 Stovall J. Bipolar disorder in adults: pharmacotherapy for acute depression. treatment responses in 51 patients. Am J Psychiatry. 1988;145(2):179-184. In: UpToDate, Keck P (Ed), UpToDate, Waltham, MA. Updated December 22, doi: 10.1176/ajp.145.2.179. 2015. Accessed on April 13, 2016. WHO Global burden of disease (GBD). World Health Organization web site. http:// SUP1 Suppes T, Leverich GS, Keck PE, et al. The Stanley Foundation www.who.int/healthinfo/global_burden_disease/gbd/en/. Accessed March Bipolar Treatment Outcome Network II: demographics and illness 15, 2016. characteristics of the first 261 patients.J Affect Disord. 2001;67(1-3):45-59. YON Yonkers KA, Vigod S, Ross LE. Diagnosis, pathophysiology, and management of mood disorders in pregnant and postpartum women. Obstet Gynecol. 2011;117(4):961-977. doi: 10.1097/AOG.0b013e31821187a7.

CPM DEVELOPMENT TEAM

Mark Foote, MD Richard Martini, MD Christopher Rich, MD Shannon Saldana, MD Richard Arbogast, MD George Nikopoulos, MD Carolyn Tometich, APRN Sam Weber, MD Nathan Parent, PharmD

This CPM presents a model of best care based on the best available scientific evidence at the time of publication. It is not a prescription for every physician or every patient, nor does it replace clinical judgment. All statements, protocols, and recommendations herein are viewed as transitory and iterative. Although physicians are encouraged to follow the CPM to help focus on and measure quality, deviations are a means for discovering improvements in patient care and expanding the knowledge base. Send feedback to Mark Foote, MD, Intermountain Healthcare, Medical Director Behavioral Health (Mark .Foote@imail org. ) or Carolyn Tometich, APRN, Intermountain Healthcare, Behavioral Health Operations Director (Carolyn Tometich@imail. org. ).