Bipolar Disorder 2. Pharmacologic Treatment Challenges with - - PDF document

SLIDE 1

Solving Clinical Challenges in

Bipolar Disorder

Terence A. Ketter, MD

Professor Emeritus Department of Psychiatry and Behavioral Sciences Stanford University School of Medicine Stanford, California

Overview

Bipolar Disorder – Solving Clinical Challenges

Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

• 1. Diagnostic Nosology

– Challenges distinguishing bipolar from unipolar

• 2. Pharmacologic Treatment

– Challenges with therapeutic vs side effects

• 3. Adverse Events

– Challenges with weight gain/sedation and akathisia 4. Non-Pharmacologic Treatment – Challenges with access to evidence-based Rx

• I. Diagnostic Nosology

Challenges with Accurate Diagnosis

Diagnostic Boundaries of Bipolar Disorder

ADHD = attention-deficit/hyperactivity disorder; CD = conduct disorder; MDD = major depressive disorder; ODD =

• ppositional defiant disorder.

Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

• Complex, variable phenomenology

– Different subtypes, mood states, courses, age-dependent presentations

• Crucial differential diagnosis

– MDD

• Confounding comorbidities

– Substance abuse, anxiety disorders – Disruptive behavioral (ADHD, ODD, CD), cluster B disorders

• Measures to enhance diagnostic accuracy

– Collateral information – DSM Screening

• Mood Disorders Questionnaire

– Beyond DSM

• Onset age, atypical symptoms, course, treatment effects,

family history

Bipolar Disorders Symptoms are Chronic and Predominantly Depressive

52.7% 31.9% 8.9% 5.9%

Asymptomatic Depressed Elevated Cycling / mixed Percent of Weeks

146 BD-I Patients

followed 12.8 years

86 BD-II Patients

followed 13.4 years 46.1% 50.3%

1.3% 2.3%

Dep:Elevated/Cycling/mixed = 14:1 Judd LL, et al. Arch Gen Psychiatry. 2003;60(3):261-269. Dep:Elevated/Cycling/mixed = 2.2:1 Judd LL, et al. Arch Gen Psychiatry. 2002;59(6):530-537.

Diagnostic Challenges – Question 1

“Patients are famous for underestimating the number and intensity of past manic or hypomanic episodes, which can lead a clinician to inappropriately diagnosing these patients with a unipolar condition. Do you have any tips for how we can better “flush out” past manic type phenomena when we are first assessing a new patient?”

SLIDE 2

Diagnostic Challenges I

Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

• Patients present with depression more than mood elevation
• Get collateral history from significant other (more

sensitive rater of mood elevation)

• Look for mood elevation symptoms

– Immediately before or after depressions – Triggered by pharmacotherapy – Mixed depressions

• In depressed patients, assess bipolar outcome risk

factors

– Depression onset prior to age 25; lifetime history of psychosis, 1° relative with mania – Presence of 1 risk factor doesn’t substantively increase bipolar

• utcome risk (which is approximately 25% overall)

– In contrast, 2 or 3 risk factors substantively increase bipolar

• utcome risk (to approximately 50% and 67%, respectively)

Substance/Medication-Induced Bipolar and Related Disorder

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth

• Edition. Arlington, VA: American Psychiatric Association; 2013.
• Prominent, persistent elevated/irritable/expansive and/or

depressed mood/anhedonia

• During/soon after substance intoxication/withdrawal or

medication exposure

• Substance/medication capable of producing above mood

symptoms

• Not better explained by non-substance induced bipolar

disorder – eg, Symptoms persist < 1 month without substance/medication

• Not merely delirium
• Distress, social/occupational impact

Antidepressant Treatment-Emergent Evolution of Bipolar I Disorder from MDD

Ketter TA (Ed). Handbook of Diagnosis and Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2010. Antidepressant Bipolar I Disorder, Manic (296.40) MDD, Single Episode, Moderate (296.22)

Severe Mild None Moderate Severe Mild Moderate

Elevation Depression

≥ 7 days or hospitalization ≥ 14 days Antidepressant discontinued

Antidepressant-Induced Mania More Common in Bipolar II Compared to Unipolar Depression

SSRI = selective serotonin reuptake inhibitor (fluoxetine, fluvoxamine, paroxetine, or sertraline); TCA = tricyclic antidepressant. Peet M. Br J Psychiatry. 1994;164(4):549-550.

Meta-Analysis from Clinical Trials Significance: TCA = SSRI > Placebo TCA > SSRI = Placebo

2 4 6 8 10 12 14

Unipolar Depression Bipolar II Depression

11.2% 3.7% 4.2% Switching to Mania (%) 0.5% 0.7% 0.2%

= N 48 242 125

3788

10,246

2716

Bipolar Mixed State Conceptualization in DSM-IV-TR vs DSM-5

Hu J, et al. Prim Care Companion CNS Disord. 2014;16(2).

Main Changes for Bipolar and Related Disorders in DSM-5 Compared to DSM-IV-TR

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth

• Edition. Arlington, VA: American Psychiatric Association; 2013.
• “with mixed features” specifier added for Manic,

Hypomanic, and Major Depressive Episodes

• Manic Episode with mixed features replaces

Mixed Episode

• Antidepressant switching – full Manic/Hypomanic

Episode emerging during antidepressant treatment and persisting beyond physiological treatment effect now sufficient for Manic/Hypomanic Episode

SLIDE 3

DSM-5 Major Depressive Episode with mixed features (AKA Mixed Depression)

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth

• Edition. Arlington, VA: American Psychiatric Association; 2013.
• Predominant, full depressive episode and ≥ 3 most days:

‒ Elevated / expansive mood – Inflated self-esteem / grandiosity ‒ Overtalkativeness – Racing thoughts ‒ Increased goal-directed activity – Impulsivity ‒ Decreased sleep need

• Mixed symptoms objectively evident, not usual behavior
• Mania trumps depression
• Not due to substance / medication

“Overlapping” Symptoms Not Included in DSM-5 Mixed Specifier

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth

• Edition. Arlington, VA: American Psychiatric Association; 2013.

Symptoms characteristic of both poles:

• Psychomotor agitation (?)
• Distractibility
• Irritability
• Insomnia per se
• Indecisiveness

Mean age = 37.5 years; P < .0001. Data from Othmer E, et al. J Clin Psychiatry. 2007;68(1):47-51. Ketter TA (Ed). Handbook of Diagnosis and Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2010.

History of Bipolar I Disorder in Outpatients with History of Major Depressive Episode

None One Two Three 10 20 30 40 50 60 70 14.7% (32/217) 19.3% (62/322) 48.8% (84/172) 66.7% (22/33) Overall 26.9% (200/744) Number of Risk Factors Percentage among Patients with History of Mania

Risk Factor Odds Ratio History of psychosis 3.28 First-degree relative with mania 2.56 Depression onset < 25 years 1.93

Diagnostic Challenges II

Akiskal HS, et al. J Affect Disord. 1983;5(2):115-128. Akiskal HS, et al. Arch Gen Psychiatry. 1995;52(2):114-123. Geller B, et al. Am J Psychiatry. 2001;158(1):125-127. Goldberg JF, et al. Am J

• Psychiatry. 2001;158(8):1265-1270.
• Additional bipolar outcome risk factors

– “Atypical” depressive symptoms

• Hyperphagia, hypersomnia, anergia

– Episode accumulation (≥ 5 lifetime depressions) – Postpartum mood elevation – Comorbid anxiety/substance use disorder – 3 consecutive generations with mood disorders – Hyperthymic/cyclothymic temperament

Most Bipolar Disorder Patients Have at Least 1 Comorbid Axis I Disorder

McElroy SL, et al. Am J Psychiatry. 2001;158(3):420-426.

10 20 30 40 50 60 70 80

None ≥ 1 ≥ 2 ≥ 3 All BD BD-I BD-II

Patients (%) Number of Lifetime Comorbid Axis I Disorders

Probabilistic Approach to Bipolar Depression

Confirmation of specific numbers requires further study. Adapted from Mitchell PB, et al. Bipolar Disord. 2008;10(1 Pt 2):144-152.

Bipolar I Depression if ≥ 5: Unipolar Depression if ≥ 4:

Symptomatology Hypersomnia Insomnia Hyperphagia Decreased appetite Psychomotor retardation Psychomotor agitation Other “atypical” symptoms Psychosis and/or pathological guilt Somatic complaints Mood lability or manic symptoms Onset and Course Earlier onset (< 25 years) Later onset (> 25 years) Multiple depressions (≥ 5 episodes) Long current depression (> 6 months) Family history Bipolar disorder No bipolar disorder

SLIDE 4

Summary of Clinical Features of Risk of Bipolar Diathesis in Depression

Akiskal HS, et al. J Affect Disord. 1983;5(2):115-128. Akiskal HS, et al. Arch Gen Psychiatry. 1995;52(2):114-123. Geller B, et al. Am J Psychiatry. 2001;158(1):125-127. Goldberg JF, et al. Am J Psychiatry. 2001;158(8):1265-1270.

• Onset

– Early, postpartum

• Depressive episodes

– Hypersomnic-retarded, catatonic, psychotic – Acute, severe, psychotic

• Comorbidity

– Substance abuse, minor antisocial acts

• Course

– Long, tempestuous course; brief well intervals – Educational, marital, occupational disruption

• Temperament

– Mood lability, energy-activity, daydreaming (BD-II)

• Family history

– Bipolar / 3 consecutive generation mood disorder

• Treatment response

– Pharmacologic hypomania (counts as BD-II in DSM-5)

Diagnostic Challenges – Question 2

“What are the strengths and limitations of DSM-5 when it comes to depressive episodes with mixed features?”

DSM-5 Bipolar Diagnostic

Strengths and Limitations

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013. Kim W, et al. Acta Psychiatr Scand. 2016;134(3):189-198; 199-206.

• DSM-5 permits mixed depressions in both bipolar disorder and

unipolar major depression – This could be good, allowing unipolar major depression subtyping and avoiding a bipolar disorder over-diagnosis

• DSM-5 doesn’t categorize concurrent threshold-level

hypomania and MDD—permitting diagnosis of major depressive episode with mixed features or hypomanic episode with mixed features – This could be good, permitting predominant pole emphasis

• DSM-5 mixed depression requires 3 (rather than 2) “non-
• verlapping” opposite pole symptoms (ie, excludes

psychomotor agitation, distractibility, and irritability) – This could be bad, making mixed depression too uncommon and not acknowledging importance of psychomotor agitation in depression

Diagnostic Challenges – Question 3

“What tools do you use in clinical arenas as standard measures of symptomology in bipolar disorder?”

Clinical Status Assessment

Sachs GS, et al. Bipolar Disord. 2002;4(5):323-327.

• Systematic Treatment Enhancement Program for Bipolar

Disorder (STEP-BD) used the Clinical Monitoring Form (CMF) to establish Clinical Status at each visit

• STEP-BD CMF Clinical Statuses included

– 4 DSM-IV syndromal episodes (Depressed, Hypomanic, Manic, Mixed) – 2 subsyndromal states (Continued Symptoms, Roughening) – 2 euthymic states (Recovered, Recovering)

• Clinical Statuses indicated if new mood interventions

were – Practically mandated (for syndromal episodes) – Elective (for subsyndromal states) – Commonly avoided, unless side effects (for euthymic states)

• II. Treatment

Challenges with Pharmacotherapy

SLIDE 5

Pharmacologic Challenges – Question 1

“New 17-year-old female patient with first serious depression, with profound slowing and hypersomnia, but has anorexia instead

• f hyperphagia. Mother and maternal

grandfather had bipolar I disorder. Would you commence an antidepressant in this young lady or would you treat her from the start with bipolar medications?”

Balancing Therapeutic and Adverse Effects

NNT = Number Needed to Treat; NNH = Number Needed to Harm. Ketter TA (Ed). Handbook of Diagnosis and Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2010.

• Benefit (Efficacy) - NNT

– Number of patients for 1 more good outcome – Lower is better – Preferably single-digit

• Risk (Tolerability) – NNH

– Number of patients for 1 more poor outcome – Higher is better – Preferably at least double-digit

• Benefit:Risk Ratio (NNT vs NNH)

– Want more benefit than risk – Strive for NNT lower than NNH

• Clinical urgency affects treatment selection

– Urgent – prioritize efficacy – Non-urgent – prioritize tolerability

Low (< 5%)

(NNH > 20)

LTG FLX, SERT, PAR, BUP, MIRT, (ES)CIT, DLX, (DES)VEN, VTX, VIL, L-MILNA

Fewer Adverse Effects

(Start here if appropriate)

Ketter TA, et al. J Affect Disord. 2014;169 Suppl 1:S24-S33.

Psychotropic Medication Adverse Effect Schematic

Adverse effect risk over placebo (NNH)

“Tolerability- First” Approach

Mood Stabilizers SGAs Anti- depressants

Medication Class Medium (5–10%)

(NNH = 10–20)

ZIP, ARI, ASN, ILO LUR, BREX, CARI Li, VPA, CBZ

High (> 10%)

(NNH < 10) More Adverse Effects

(Go here if necessary)

CLZ OLZ RSP, QTP

Older Newer Older Newer

Pharmacologic Challenges – Question 2

“How early in treatment should we be using lithium?”

Pharmacologic Challenges – Answer

Ketter TA (Ed). Handbook of Diagnosis and Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2010.

“Use lithium early in treatment (generally before antipsychotics, but commonly after psychotherapy/antidepressants/lamotrigine) – especially for acute and preventive treatment of mood elevation.”

FDA-Approved Agents for Bipolar Disorder

*Adjunctive and monotherapy. ER, XR, ERC = extended release oral; LAI = long-acting injectable. Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

Acute Mania Year Drug

1970 Lithium 1973 Chlorpromazine 1994 Divalproex, ER (2005) 2000 Olanzapine* 2003 Risperidone* 2004 Quetiapine, XR (2008)* 2004 Ziprasidone 2004 Aripiprazole* 2004 Carbamazepine ERC 2009 Asenapine* 2015 Cariprazine

Longer Term Year Drug

1974 Lithium 2003 Lamotrigine 2004 Olanzapine 2005 Aripiprazole* 2008 Quetiapine, XR (adjunct) 2009 Risperidone LAI* 2009 Ziprasidone (adjunct)

Acute Depression Year Drug

2003 Olanzapine+fluoxetine combination 2006 Quetiapine, XR (2008) 2013 Lurasidone*

Unmet Need Unmet Need

Important unmet needs – well-tolerated treatments for acute depression and maintenance.

SLIDE 6

• III. Side Effects

Management during Pharmacotherapy

Most Common/Problematic Side Effects

Ariov T. Psych Congress Network. www.psychcongress.com/article/top-5-side-effects-psychotropics-and-how-manage-them. Accessed June 6, 2017. Ketter TA (Ed). Handbook of Diagnosis and Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2010.

Ariov T (2016) ‒ The Top 5 Side Effects of Psychotropics and How to Manage Them 1. Weight Gain 2. Anhedonia and Emotional Flattening 3. Sleep Disturbances 4. Sexual Dysfunction 5. Hyperprolactinemia Ketter TA (2010) 1. Weight Gain (3 questions from 2017 Psych Congress attendees)

• How to address weight gain in bipolar disorder?
• Specific weight gain management tips (beyond usual diet and

exercise)?

• How to deal with weight gain and antimanic agents?

2. Akathisia (1 question from 2017 Psych Congress attendees)

• How to address antipsychotic akathisia in bipolar depression?

Managing Medication Side Effects

BMI = body mass index. Ketter TA (Ed). Handbook of Diagnosis and Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2010.

• Carefully assess baseline (eg, BMI, drowsiness,

agitation/anxiety)

• Prior to intervention, warn of side/adverse effect risks

– Especially weight gain/sedation and akathisia

• Assess specific adverse effects risks (eg,

weight/sedation/akathisia) – Age, gender, baseline weight/sedation/akathisia, medical disorders, medications

• Assess both potential benefits and harms of

interventions

• Consider current mood state

– Affects antidepressant/antipsychotic need/tolerability

Side Effect Challenges – Question 1

“How to address weight gain in bipolar disorder?”

Pharmacotherapy and Weight Gain in Bipolar Disorder

Ketter TA (Ed). Handbook of Diagnosis and Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2010.

• Limited FDA-approved weight control treatments

– Commonly not covered by insurance

• Antidepressants (before Mood Stabilizers)

– Bupropion, non-paroxetine SSRIs, SNRIs – Before mirtazapine, paroxetine, MAOIs, TCAs – Mood Stabilizers (before Antipsychotics)

• Lamotrigine before lithium, before valproate
• Carbamazepine in reserve for manic symptoms (less weight gain risk vs

lithium, valproate) – But more treatment complexity (drug interactions and side effects)

• Antipsychotics (only if absolutely necessary)

– Cariprazine, lurasidone, aripiprazole before quetiapine before risperidone – Ziprasidone (weight loss, but akathisia/unpredictable mood effects) in reserve – Olanzapine/clozapine (profound weight gain risk, but superior mood efficacy) in reserve – Very low dose olanzapine (1.25 mg/day) or clozapine (12.5 mg/day) may limit weight gain – Olanzapine-fluoxetine combination – minimal olanzapine, maximal fluoxetine – ≥ 7% gain – potentially significant, > 5 lb gain in 1st 3 weeks – ultimate catastrophic risk

Adjunctive Non-Stimulant Medications to Counter Weight Gain in Bipolar Disorder

Some brand names are listed for participant clarification purposes only. No product promotion should be inferred. Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

• Topiramate 100–200 mg/day off-label, also

– ≤ 92 mg/day + ≤ 15 mg/day phentermine in Qsymia™ on- label, independently off-label

• Zonisamide 300–400 mg/day off-label
• Metformin ≤ 2000 mg/day off-label
• Bupropion 300–450 mg/day off-label, also

– ≤ 360 mg/day + ≤ 32 mg/day naltrexone in Contrave™ on- label, independently off-label

• Naltrexone ≤ 50 mg/day off-label, also

– ≤ 32 mg/day + ≤ 360 mg/day bupropion in Contrave™ on- label, independently off-label

• Liraglutide (daily subcutaneous injections) on-label

– From experienced medical provider

• Orlistat ≤ 360 mg/day on-label, but commonly yields diarrhea

SLIDE 7

Adjunctive Stimulant/Stimulant-like Medications to Counter Weight Gain in Bipolar Disorder

Some brand names are listed for participant clarification purposes only. No product promotion should be inferred. Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

• Some agents have abuse potential
• Long half-life agents for evening appetite attenuation, less

abuse risk

• Can yield anxiety/agitation/restlessness

– Lower doses, anxiolytics/dopamine blockers may address such problems

• Lisdexamfetamine ≤ 70 mg/day off-label
• Phentermine ≤ 37.5 mg/day on-label, also

– ≤ 15 mg/day + topiramate ≤ 92 mg/day in Qsymia™ on- label, independently off-label

• Armodafinil ≤ 250 mg/day off-label
• Atomoxetine ≤ 250 mg/day off-label
• Levomilnacipran ≤ 120 mg/day off-label
• Lorcaserin (heart valve risk ?) on-label

– From experienced medical provider

Side Effect Challenges – Question 2

“How to address antipsychotic akathisia in bipolar depression?”

Pharmacotherapy and Akathisia in Bipolar Disorder

Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

• No FDA-approved anti-akathisia treatment

– Reducing dose(s) of offending agent(s) commonly most helpful

• Anxiolytics/calming agents (before Mood Stabilizers?)

– Lorazepam ‒ abuse potential; pramipexole/mirtazapine ‒ mood destabilization potential

• Mood Stabilizers (before Antipsychotics)

– Lithium, valproate, carbamazepine, lamotrigine unlikely to exacerbate akathisia

• Antipsychotics (before Activating Agents)

– Quetiapine before risperidone before olanzapine before clozapine before – Lurasidone before cariprazine/aripiprazole (akathisia risks) – Ziprasidone (akathisia risk and unpredictable mood effects) in reserve – Olanzapine/clozapine (superior efficacy, low akathisia risk, but high weight gain risk) in reserve

• Off-label brexpiprazole may have utility in some patients
• Activating Agents (only if absolutely necessary)

– Activating (eg, levomilnacipran) only after calming (eg, paroxetine) antidepressants – Stimulants/Stimulant-like agents commonly need to be avoided

• IV. Treatment

Challenges with Non-pharmacologic Treatments

Non-Pharmacologic Treatment Challenges – Question 1

“Which non-pharmacologic treatments for bipolar disorder do you offer and what are their success rates?”

Adjunctive Non-Pharmacologic Treatments for Bipolar Disorder

CBT = cognitive-behavioral therapy; DBS = deep brain stimulation; ECT = electroconvulsive therapy; IPSRT = interpersonal and social rhythm therapy; TMS = transcranial magnetic stimulation. Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

• Adjunctive Evidence-Based Psychotherapies

– CBT, IPSRT, Family-Focused, Psychoeducation, Functional Remediation – Single-digit NNTs

• Adjunctive Neuromodulation

– TMS, ECT, ± DBS – Some have single-digit NNTs

• Success rates comparable to approved

pharmacotherapies – Single-digit NNTs

SLIDE 8

Non-Pharmacologic Treatment Challenges – Questions 2 and 3

“What non-pharmacologic treatments do you recommend to a busy community-based psychiatrist?” “Which forms of psychotherapy have the strongest supportive evidence in treatment

• f bipolar disorder?”

**P < .01, ***P < .001 vs control.

Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

Overview of Adjunctive Psychosocial Maintenance Studies

NNT for Relapse/Recurrence Prevention, Rates

NNT 4 4 6

Cognitive Therapy vs No Psychotherapy Family Focused Therapy vs Crisis Management Psychoeducation Group vs Non-structured Group

After Sustained Recovery After Acute Episode When Euthymic / Subsyndromal

Contemporary Manualized Intensive Psychotherapy Studies

20 40 60 80 100

= N

No Psychotherapy

75.0% 48

Crisis Management

54.3% 70

Non-structured Group

91.7% 60

Relapse/Recurrence (%)

Colom 03 Miklowitz 03 Lam 03

Cognitive Therapy

31.3% 43.8% 48

**

Family Focused Therapy

18.8% 35.5% 31

**

Psychoeducation Group

25.0% 66.7% 60

***

Psychotherapies had single-digit NNTs, comparable to approved pharmacotherapies.

Symptomatic Much More Than Functional Recovery in Bipolar Disorder

Dion GL, et al. Hosp Community Psychiatry. 1988;39(6):652-657.

Mild or No Affective Symptoms Employed Full Time at Expected Level 25 50 75 100 Patients (%) 78% (33/42) 21% (9/42) 6 Months after Hospitalization Pre-Treatment

±P < .06 vs PE; **P < .001 vs TAU. Error bars are SEs of means. Completion rates: FR 71.4%, PE 75.6%, TAU 82.5% (NS). FR = Paper-and-pencil tasks/group exercises for memory, attention, problem solving, reasoning, multitasking, and organization.

Torrent C, et al. Am J Psychiatry. 2013;170(8):852-859.

21 Weekly 90-Minute Adjunctive Functional Remediation (but not Psychoeducation) Sessions Diminished Dysfunction in “Recovered” Bipolar Disorder Patients

***

Functional Remediation (n = 77) Psychoeducation (n = 82) Treatment-As-Usual (n = 80)

Post-Treatment Functional Impairment

(Functioning Assessment Short Test) 20 22 24 26 28 30 32 34

±,

Improvement from Baseline Effect Size

0.22 0.41 0.93 Pre-Treatment

Conclusions

Bipolar Disorder – Solving Clinical Challenges

Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

• 1. Diagnostic Nosology

– Challenges distinguishing bipolar from unipolar 2. Pharmacologic Treatment – Challenges with therapeutic vs side effects 3. Adverse Events – Challenges with weight gain/sedation and akathisia 4. Non-Pharmacologic Treatment – Challenges with access to evidence-based Rx

Practical Take-Aways

Bipolar Disorder – Solving Clinical Challenges

Ketter TA (Ed). Advances in Treatment of Bipolar Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2015.

• Diagnosis

– Collateral significant other history crucial

• Pharmacologic Treatment

– Prioritize FDA-approved interventions

• Adverse Effects

– Balance therapeutic AND adverse effects, integrating urgency – Antidepressants before mood stabilizers before antipsychotics

• Non-Pharmacologic Treatment

– Psychoeducation, Family-Focused, IPSRT, CBT – Functional Remediation