3.2 Bipolar and Related Disorders

Bipolar and Related Disorders

Exam Tip: The presence of psychotic features or the need for hospitalization during an elevated mood state automatically qualifies the episode as mania, ruling out hypomania and Bipolar II.

1. Mania vs. Hypomania

The fundamental distinction in the bipolar spectrum rests on differentiating a manic episode from a hypomanic episode.

Manic Episode (DSM-5-TR)

• Criterion A (Duration): A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).
• Criterion B (Symptoms): At least 3 of the following (4 if the mood is only irritable):
  • Inflated self-esteem or grandiosity
  • Decreased need for sleep (e.g., feels rested after 3 hours)
  • More talkative than usual or pressure to keep talking
  • Flight of ideas or racing thoughts
  • Distractibility
  • Increase in goal-directed activity or psychomotor agitation
  • Excessive involvement in activities with a high potential for painful consequences (e.g., spending sprees, sexual indiscretions)
• Criterion C (Severity): Causes marked impairment in social/occupational functioning, necessitates hospitalization, or includes psychotic features.
• Criterion D: Not attributable to substance effects or another medical condition.

Hypomanic Episode (DSM-5-TR)

• Duration: Lasts at least 4 consecutive days.
• Symptoms: Same symptom list as mania.
• Severity: The episode is an unequivocal change in functioning, observable by others, but it is not severe enough to cause marked impairment, does not require hospitalization, and has no psychotic features.

2. Bipolar Disorders Classification

Bipolar I Disorder

• Requirement: At least one manic episode.
• Depression: Major depressive episodes often occur but are not required for the diagnosis.
• Key Note: If a patient has a manic episode, they are Bipolar I, regardless of their history of depression or hypomania.

Bipolar II Disorder

• Requirement: At least one hypomanic episode AND at least one major depressive episode.
• Exclusion: There has never been a manic episode.
• Clinical Picture: Patients typically seek treatment during depressive episodes. A careful history is required to uncover past hypomanic episodes; screen for hypomania using tools such as the Mood Disorder Questionnaire (MDQ).

Bipolar II vs. Borderline Personality Disorder (Differential Diagnosis)

Both conditions involve mood instability and impulsivity, but the distinction is critical for pharmacotherapy. Bipolar II mood episodes are episodic, last days to weeks, are driven by biological cycling, and are accompanied by neurovegetative symptoms. Borderline Personality Disorder affective instability is reactive to interpersonal stressors, lasts hours to days, and is accompanied by fear of abandonment, identity disturbance, and self-harm. Antidepressant monotherapy can trigger manic switches in bipolar II; in BPD, mood stabilizers have limited benefit and dialectical behavior therapy is first-line.

Cyclothymic Disorder

• Duration: For at least 2 years (1 year in children/adolescents), there have been numerous periods with hypomanic symptoms that do not meet criteria for a hypomanic episode and numerous periods with depressive symptoms that do not meet criteria for a major depressive episode.
• Persistence: Symptoms have been present for at least half the time, and the individual has not been without symptoms for more than 2 months at a time.

Specifiers

• With rapid cycling: The presence of at least 4 mood episodes (major depressive, manic, or hypomanic) in the previous 12 months. Predicts poorer response to lithium and increased risk of antidepressant-induced cycling.
• With mixed features: A manic/hypomanic episode with at least 3 depressive symptoms, or a depressive episode with at least 3 manic/hypomanic symptoms. Mixed states carry elevated suicide risk and respond better to valproate than to lithium.
• With melancholic features, with atypical features, with peripartum onset, with seasonal pattern: Apply the same definitions used for depressive disorders.

3. Treatment Strategies for Bipolar Disorder

The cornerstone of bipolar treatment is mood stabilization. Antidepressant monotherapy is generally contraindicated as it may induce a manic switch or rapid cycling; if an antidepressant is required, it should be combined with a mood stabilizer and avoided in rapid cyclers.

Mood Stabilizers

• Lithium (Lithobid): Gold standard for acute mania and maintenance.
  • Therapeutic level: 0.6 to 1.2 mEq/L. Toxic at > 1.5 mEq/L.
  • Toxicity signs: Tremor, ataxia, vomiting, confusion, seizures.
  • Long-term risks: Hypothyroidism, nephrogenic diabetes insipidus, Ebstein's anomaly (teratogenic — lithium is pregnancy category D but may still be used when benefits outweigh risks).
  • Monitoring: Baseline and periodic TSH, free T4, BUN/Cr, urinalysis, lithium level (checked 12 hours post-dose, steady state at 5 days).
• Valproic Acid / Divalproex (Depakote): Excellent for rapid cycling and mixed states.
  • Therapeutic level: 50 to 125 mcg/mL.
  • Risks: Hepatotoxicity, pancreatitis, weight gain, teratogenicity (neural tube defects — give folate). Monitor LFTs, ammonia, valproate level, and CBC.
• Carbamazepine (Tegretol):
  • Therapeutic level: 4 to 12 mcg/mL.
  • Risks: Agranulocytosis, aplastic anemia, Stevens-Johnson syndrome (especially in Asian descent with HLA-B*1502 allele). Induces CYP3A4; reduces effectiveness of oral contraceptives.
• Lamotrigine (Lamictal): Best for bipolar depression maintenance; not effective for acute mania.
  • Risks: Stevens-Johnson syndrome and toxic epidermal necrolysis. Requires slow titration (25 mg weekly x 2, then 50 mg weekly) and dose adjustment when combined with carbamazepine (faster metabolism) or valproate (slower metabolism — half the dose).

Atypical Antipsychotics

Many SGAs are FDA-approved across bipolar phases. For acute mania: Aripiprazole, Risperidone, Quetiapine, Olanzapine, Asenapine. For bipolar depression: Quetiapine, Lurasidone, Olanzapine-fluoxetine combination (OFC). For maintenance: Aripiprazole, Lamotrigine, Lithium. Monitor for metabolic syndrome, akathisia (especially with aripiprazole), and sedation (especially with quetiapine and olanzapine).

Clinical Vignette: A 28-year-old female presents with severe depression. She reports that 3 years ago, she had a 5-day period where she felt "on top of the world," slept only 2 hours a night, started a new business, and felt highly productive. Her friends noticed the change, but she continued going to work and was not hospitalized. She has never experienced hallucinations. Diagnosis: Bipolar II Disorder (Current Major Depressive Episode, history of Hypomania).

Worked Example — Mixed Features: A 40-year-old male presents with depressed mood, anhedonia, and fatigue for 2 weeks, but also describes racing thoughts, pressured speech, and decreased need for sleep. He meets criteria for a major depressive episode with mixed features (3+ hypomanic/ manic symptoms during a depressive episode). This presentation carries elevated suicide risk and favors a mood stabilizer (valproate) over lithium.