bipolar disorder
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Bipolar Disorder
Definition and Classification
Bipolar disorder (BD) is a recurrent mood disorder characterized by episodes swinging between mania and depression. The DSM-5 recognizes several subtypes:
- Bipolar I: At least one full manic episode (lasting ≥7 days, or any duration if hospitalization required); major depressive episodes are common but not required for diagnosis
- Bipolar II: Recurrent major depressive episodes + at least one hypomanic episode (≥4 days); no full mania
- Cyclothymic disorder: Numerous periods of hypomanic and depressive symptoms over ≥2 years, not meeting full criteria for either episode
- Bipolar NOS: Does not fit above categories but has clear bipolar features
Historically referred to as "manic-depressive insanity" by Emil Kraepelin.
- Principles of Neural Science, 6th ed., p. block11
Epidemiology
- 12-month prevalence of bipolar I: ~0.6%; bipolar spectrum disorders ~1-3%
- Slightly higher prevalence in males
- Average age at onset: late adolescence to early adulthood
- Childhood onset is possible but diagnostically difficult (overlap with ADHD)
- Late-onset mania (midlife+) is often secondary to medical conditions or substances rather than idiopathic BD
- Goldman-Cecil Medicine, p. 3760
Pathobiology
- Etiology remains unclear but is strongly genetic: heritability ~50%, polygenic and multifactorial
- Specific gene loci identified in rare families; no single unifying pathophysiological mechanism yet
- Frontostriatal dysregulation is likely central to clinical manifestations
- Structural neuroimaging: increased ventricular-brain ratios (parenchymal atrophy)
- Circadian rhythm disruption: phase advancement of central circadian rhythms can precipitate mania - decreased sleep triggers further phase advancement, creating a vicious cycle
- Psychosocial stressors can precipitate both manic and depressive episodes
- A major 2025 genomic meta-analysis in Nature (PMID 39843750) yielded new biological and phenotypic insights, confirming polygenicity
Clinical Manifestations
Manic Episode (DSM-5 criteria)
A distinct period of abnormally elevated, expansive, or irritable mood PLUS abnormally increased goal-directed activity or energy, lasting ≥1 week, most of the day, nearly every day, AND 3 or more of the following (4 if mood is only irritable):
| Domain | Symptoms |
|---|---|
| Emotional | Euphoria, irritability, labile affect |
| Ideational | Inflated self-esteem / grandiosity, racing thoughts, flight of ideas |
| Somatic | Increased energy, decreased need for sleep, psychomotor agitation, distractibility |
| Behavioral | Pressured speech, goal-directed hyperactivity, excessive involvement in pleasurable activities with high risk of harm (spending, hypersexuality, gambling) |
Psychotic features (delusions, hallucinations, loose associations) may occur in severe mania - defining "mania with psychotic features." Psychosis outside mood episodes should prompt reconsideration of the diagnosis.
Hypomanic Episode
Same symptom criteria as mania but lasting only ≥4 days, not severe enough to cause marked impairment or require hospitalization, and with no psychotic features.
Depressive Episodes in BD
Full major depressive episodes (same criteria as unipolar MDD) are common in bipolar I and define bipolar II.
Diagnosis
- Based on history and clinical examination
- Must rule out: medical conditions (thyroid disease, CNS lesions, neurologic disorders), substances/medications, and other psychiatric conditions (schizophrenia, borderline personality disorder)
- In delirium or dementia, manic/depressive symptoms are accompanied by cognitive deficits
- Patients can have purely manic episodes ("unipolar mania") and still be diagnosed bipolar I
Treatment
Treatment initiation and major changes should be supervised by a psychiatrist.
Mood Stabilizers (First-line)
| Drug | Target Dose | Target Level | Key Notes |
|---|---|---|---|
| Lithium | 600-1500 mg/day (divided) | 0.6-1.2 mEq/L (up to 1.4 in acute mania) | Best evidence; reduces suicide risk; monitor renal function, TFTs, calcium |
| Valproic acid | 500-1500 mg/day | 50-100 μg/mL | Lithium + valproate superior to valproate alone for relapse prevention |
| Carbamazepine | 400-1200 mg/day | 4-12 μg/mL | Less commonly used; many drug interactions |
| Lamotrigine | 25 mg start → max 200 mg/day (slow titration) | -- | Prophylaxis against depressive episodes; risk of Stevens-Johnson syndrome with rapid titration |
- Goldman-Cecil Medicine, p. 3761
- A 2024 systematic review and meta-analysis (PMID 38750644) specifically evaluated lamotrigine's efficacy in BD, confirming its stronger effect on the depressive pole.
Antipsychotics (FDA-approved for Bipolar I)
Several second-generation antipsychotics (SGAs) are approved for BD maintenance: olanzapine, quetiapine, aripiprazole, and others.
- Often added to a mood stabilizer; combination of antipsychotic + lithium or valproate is more effective for both manic and depressive symptoms than mood stabilizer alone
- Kaplan & Sadock's Comprehensive Textbook of Psychiatry, block47
- Caution: SGAs can precipitate metabolic syndrome and (less commonly) tardive dyskinesia; reserve for maintenance when other stabilizers fail or are not tolerated
Psychotherapy
Adjunctive psychotherapy goals include:
- Psychoeducation for patient and family
- Symptom management and coping skills
- Improving social/family/occupational functioning
- Relapse prevention planning
- Textbook of Family Medicine, 9e, p. 598
Acute Mania
- Mood stabilizer ± antipsychotic for rapid control
- Benzodiazepines (short-term) for agitation/sleep
- Remove precipitating triggers (sleep deprivation, stimulants)
Bipolar Depression
- Quetiapine, lurasidone, lamotrigine are preferred
- Standard antidepressants are used cautiously (risk of triggering mania or cycle acceleration) and generally only with a mood stabilizer on board
Special Populations
Pediatric BD
- Prevalence ~3% for bipolar spectrum in those under 18
- Adult DSM criteria are challenging to apply; many children "rapid cycle" multiple times/day
- AACAP recommends using DSM criteria for consistency ("narrow phenotype")
- First-line: lithium or anticonvulsants; few RCTs exist in children
- Distinguish from Disruptive Mood Dysregulation Disorder (DMDD), a separate DSM-5 diagnosis for chronic, severe irritability with temper outbursts
Pregnancy
- Bipolar disorder in pregnancy requires careful risk-benefit analysis (covered in Creasy & Resnik's Maternal-Fetal Medicine); some mood stabilizers carry teratogenic risk (especially valproate)
Key Points Summary
- Bipolar I = at least one manic episode; Bipolar II = hypomania + major depression, never full mania
- Genetic factors account for ~50% of risk; circadian rhythm disruption is a key physiological trigger
- Lithium remains the gold-standard mood stabilizer with the best evidence for both mania prevention and suicide reduction
- Lamotrigine is preferred for bipolar depression prophylaxis
- SGAs are effective adjuncts but carry metabolic risks in long-term use
- Goal of modern treatment is full remission, not just symptom reduction
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