Chapter 10: Bipolar Disorders

1. Chapter 10:Bipolar Disorders David J. Miklowitz Sheri L. Johnson

2. Diagnosis: Diagnostic Features • Insomnia or hypersomnia • Psychomotor agitation or retardation, • Changes in weight or appetite • Loss of energy • Difficulty concentrating or making decisions • Feelings of worthlessness or guilt • Suicidal ideation or behavior • Severe changes in mood, thinking, and behavior, from extreme highs to lows • Distinctive “episodes” lasting a few days to a year or more. • Depressive episode: ≥ Five of the following for 2 weeks or longer with significant distress and/or decline in functioning • Intense sadness and/or loss of interest must be present

3. Diagnosis: Manic and Hypomanic Episodes • Manic episode: Notably different elated, expansive, or irritable mood with ≥ 3 (≥ 4 if irritable) of the following lasting for at least 1 week and causing significant distress or impairment: • Inflated self-esteem (grandiosity) • Decreased need for sleep • Racing thoughts or flight of ideas • Rapid or pressured speech • Reckless and impulsive behavior • Enhanced energy • Increased goal-directed activity • Distractibility • Hypomanic episode: Same symptom criteria, but… • Shorter (4 days instead of 1 week) • Not severe enough to cause marked impairment in functioning (no psychotic features and no hospitalization)

4. Diagnosis: Diagnostic Criteria • Bipolar I (BD-I) • Criteria met for at least 1 manic episode • Not better explained by a schizophrenia spectrum disorder (e.g., schizophrenia) • Bipolar II (BD-II) • Criteria met for at least one hypomanic episode and one depressive episode • Criteria never met for manic episode • Not better explained by schizophrenia spectrum disorder

5. Diagnosis: Related Conditions • Bipolar disorder not elsewhere classified • Patients with brief and recurrent manic or hypomanic phases that fall short of the duration criteria • Cyclothymia • 2 or more years of switching between hypomanic and depressive symptoms that do not meet the full DSM-5 criteria for a hypomanic or a major depressive episode

6. Diagnosis: Some Potential Specifiers • With mixed features: Features of depressive episode present during manic episode or vice versa • More debilitating course of illness, earlier onset, and greater comorbidity with anxiety and substance use disorders • Rapid cycling: Four or more episodes of depression, mania, or hypomania in 1 year • 10%–20% of cases, more common in bipolar II and women

7. Diagnosis: Changes in DSM-5 • Increased activity is now a cardinal (Criterion A) symptom • Helps diagnose people who can describe behavior well but not internal experience • Mixed episode specifier no longer requires meeting full criteria for mania and depression simultaneously

8. Diagnosis: Comorbid Disorders • Virtually all bipolar patients have a lifetime history of other psychiatric disorders • Anxiety disorders (62.9%) • ADHD and/or oppositional defiant disorder (44.8%) • Substance use disorders (36.8%) • In children, comorbidity of BD with ADHD is between 60% and 90%

9. Symptoms: Presentation Differences • Patients with bipolar II disorder spend the majority of their ill weeks depressed, not hypomanic (ratio of 37 to 1) • Bipolar I ratio is about 3:1 • 80% of youths show irritability and grandiosity, whereas 70% have elated mood, decreased need for sleep, or racing thoughts • Less frequent symptoms: hypersexuality and psychotic symptoms

10. Symptoms: Suicidality • Among those hospitalized for BD, 15x greater risk for completed suicide than the general population • 4x greater risk than patients with major depressive disorder • Risk factors: • Comorbid alcohol or substance abuse • Younger age • Recent illness onset • Male gender • Prior suicide attempts • Family history of suicide • Rapid cycling course • Social isolation • Anxious mood • Recent severe depression • “Impulsive aggression”

11. Prognosis • Majority of patients with BD experience significant impairment in work, social, and family functioning during and after illness episodes • One third work full time outside of the home • More than half unable to work or work only in sheltered settings • Negative predictors: subsyndromal depressive symptoms following a manic episode and cognitive dysfunction • 1 in 10 BD-II patients eventually develop a full manic or mixed episode and are then diagnosed with BD-I

12. Epidemiology • 1% meet lifetime criteria for BD-I; 1.1% for BD-II • 2.4% meet criteria for subthreshold BD; 4.2% cyclothymia • Mean age at onset • 18.4 years BD-I • 20.0 years BD-II • 21.9 years subthreshold BD • Between 50% and 67% of BD-I and BD-II have onset before age 18 • 15% and 28% before age 13 • In community studies, 25% to -33% of bipolar I patients have unipolar mania

13. Etiology: Expressed Emotion • Expressed emotion attitudes (EE) - criticism, hostility, or emotional overinvolvement • Affective negativity (AE): Criticism, hostility, or guilt induction • BD patients who return home to high EE or AE families are at ~94% risk for relapse within 9 months • ~17% returning to low EE and AE families

14. Etiology: Unipolar Depression Overlap • Predictors of recurrent and severe symptoms in both disorders include low social support, family EE, and neuroticism • Negative life events equally predictive of relapse • Heritability for unipolar depression and mania modestly correlated, but 71% of genetic liability to mania is distinct from depression • Variables that influence the course of unipolar depression also influence BD depression

15. Etiology: Stress • BD patients with high levels of stressful life events are at 4.5x greater risk for relapse within 2 years • Number of prior episodes of illness does not interact with life events stress in predicting recurrences • Contrary to kindling model • Patients with severe early adversity (e.g., parental neglect or sexual/physical abuse) report less stress prior to illness recurrences and earlier age at onset • Supports stress sensitization model

16. Etiology: Reward Sensitivity and Goal Setting • People with a history of mania describe themselves as more likely to react with strong emotions to reward cues (reward sensitive) • Elevated reward sensitivity predicts BD onset and a more severe course of mania among BD-I patients • Goal-attainment-type life events predict increases in manic symptoms but not depressive symptoms • Highly ambitious life goals/goal setting associated with more severe course of mania and onset of BD

17. Etiology: Brain Systems • Abnormally strong activity in the dopaminergic pathways involved in reward sensitivity • Nucleus accumbens and the ventral tegmentum • Reduced connectivity between limbic (emotion-related) brain regions and prefrontal regions • May explain why patients with bipolar disorder have unstable mood and hyperreactivity to events • Diminished activity of the PFC might interfere with the ability to inhibit emotions and to conduct effective planning and goal pursuit

18. Biological Etiology: Heritability • Genetic studies show bipolar disorder is among the most heritable of disorders. Heritability estimates from twin studies are as high as .85 to .93 • Risk of bipolar disorder among first-degree relatives between 5% and 12% • Risk of all forms of mood disorder between 20% and 25% • Monozygotic twins of BD-I patients are at an increased risk for schizophrenia (13.6%) and mania (36.4%)

19. Biological Etiology: Neurotransmitters • Research emphasis has shifted from absolute levels of neurotransmitters to the overall functioning of systems • Neural plasticity and disturbed intracellular signaling cascades rather than the amount of dopamine or serotonin • Dopamine theory: Dopamine function is enhanced during mania and diminished during depression • Dopamine precursors, such as l-dopa, can trigger mania • Mood disorders generally associated with decreased serotonin receptor sensitivity

20. Treatment- Lithium Medication and Nonadherence • Lithium: A mood stabilizer • 60% to 70% improve on lithium during a manic episode • Also helps prevent relapse • Significant side effects: sedation, weight gain, tremors of the hands, stomach irritation, thirst, and kidney problems • 40% to 60% of patients are fully or partially nonadherent with stabilizer regimens in the year after a manic episode • In community, patients take lithium for an average of only 2 to 3 months • Rapid discontinuation of lithium places patients at higher risk for recurrence and suicide

21. Treatment: Pharmacological: Anticonvulsants/Mood Stabilizers • Divalproex sodium (Depakote) is as effective as lithium in controlling manic episodes • Generally more benign side effects: stomach pain, nausea, weight gain, elevated liver enzymes, and lowering of blood platelet counts • Combination therapy and lithium alone both more effective than divalproex alone in preventing relapse • Other anticonvulsants/mood stabilizers • Carbamazepine (Tegretol), lamotrigine (Lamictal), and oxcarbazepine (Trileptal)

22. Treatment: Pharmacological: Suicide Prevention • Patients treated with lithium, antipsychotics, or antidepressants (especially in combination regimens) have lower suicide rate • Lithium was more effective than divalproex sodium in reducing suicide attempts and completions

23. Treatment: Pharmacological Other Medications • Olanzapine (atypical antipsychotic medication) • Prevention of recurrences of mania or mixed episodes is as good or better than lithium or divalproex • Concerns about side effects: weight gain and metabolic syndrome • Quetiapine, risperidone, aripiprazole, and ziprasidone are alternatives with lower side-effect risk • Not clear that combinations of SSRI and mood stabilizer are effective for treating BD depression • Risk of more frequent mood cycles

24. Treatment: Group Psychotherapy • Structured group psychoeducation • Education about BD, relapse, and importance of medication • After 2 years, relapse is 67% vs. 92% in controls, and fewer hospitalized • More likely to maintain lithium levels within the therapeutic range • Group treatment is most cost-effective form of psychotherapy • Integrated CBT group treatment for bipolar adults with comorbid substance dependence • Focuses on the overlap between the cognitions and behaviors of both conditions during recovery and relapse • About half as many days of substance use as those receiving only drug counseling

25. Treatment: Individual Psychotherapy • Interpersonal and Social-Rhythm Therapy (IPSRT) • Stabilize social rhythms and resolve interpersonal problems that precede episodes • Track daily routines and sleep/wake cycles and identify events that change those routines • Delays recurrence if begun during acute phase • Individual psychoeducational treatment and medication • 7 to 12 sessions • 30% reduction in mania relapse, longer time before relapse, and enhanced social functioning

26. Treatment: Family Focused Treatment (FFT) • Group therapy with patient and family • Goal: Reduce high EE attitudes and enhance communication • Psychoeducation about BD and develop relapse prevention drill • Communication-enhancement training • Problem-solving skills training • Efficacy vs. standard care over 2 years • Less likely to relapse (17% vs. 52%) • Greater improvements over time in depression, manic symptoms, and better adherence to medications

27. Treatment: Psychotherapy Efficacy Comparison (STEP-BD) • 30 sessions of IPSRT, FFT, or CBT over 9 months for BD-I and BD-II starting in depressed episode • Control condition was three sessions of psychoeducation; medication prescribed in all conditions • Treatment conditions more likely to recover rapidly from depression, remain well, better overall functioning, relationship functioning, and life satisfaction • One-year rates of recovery same across intensive therapy groups