bipolar disorders

**DEFINITIONS (DSM-5-TR)** - **Manic episode:** Abnormally elevated, expansive, or irritable mood PLUS increased energy/activity lasting ≥1 week (or any duration if hospitalization is required). It causes marked functional impairment and may include psychosis. Need ≥3 of the DIG FAST symptoms (4 if mood is only irritable): Distractibility, Indiscretion (risky behavior), Grandiosity, Flight of ideas, Activity/psychomotor agitation, Sleep decreased need, Talkativeness/pressured speech. - **Hypomanic episode:** Same symptoms lasting ≥4 days, but with NO marked impairment, NO psychosis, and NO hospitalization. The change in functioning is observable by others. - **Major depressive episode:** ≥2 weeks of depressed mood or anhedonia plus other symptoms (SIG E CAPS: Sleep, Interest, Guilt, Energy, Concentration, Appetite, Psychomotor changes, Suicidality).

**SUBTYPES** - **Bipolar I:** ≥1 manic episode. Depressive episodes are common but not required. Men and women are equally affected. - **Bipolar II:** ≥1 hypomanic episode AND ≥1 major depressive episode, with NO history of mania. It is more common in women. Patients often present during a depressive episode, so it is commonly misdiagnosed as unipolar depression. - **Cyclothymic disorder:** ≥2 years (1 year in children/adolescents) of numerous hypomanic and depressive symptoms that do not meet full criteria for either episode. - **Specifiers:** Rapid cycling (≥4 episodes/year), mixed features, psychotic features, and others.

**EPIDEMIOLOGY AND PATHOPHYSIOLOGY** - Lifetime prevalence is ~1% for bipolar I. Mean age of onset is late teens to early 20s. - It is highly heritable (~80–90% heritability; monozygotic twin concordance is ~40–70%). Polygenic, with implicated genes including CACNA1C and ANK3. - Proposed mechanisms include dysregulated monoamines (↑ dopamine/norepinephrine in mania), altered intracellular signaling, and circadian rhythm disruption. - Comorbidities are common: substance use, anxiety disorders, ADHD. Suicide risk is high (~15–20% lifetime mortality from suicide).

**DIFFERENTIAL AND MIMICS (high-yield)** - **Substance-induced:** cocaine, amphetamines, and steroids can cause manic-like symptoms. - **Medical causes:** hyperthyroidism, MS, frontal lobe lesions/tumors, Cushing syndrome, and neurosyphilis. - **Antidepressant-induced mania:** a manic switch on antidepressant monotherapy suggests underlying bipolar disorder. - **Schizoaffective disorder:** psychosis persists ≥2 weeks without mood symptoms. In bipolar disorder, psychosis occurs only during mood episodes. - **ADHD and borderline personality disorder** can also overlap.

**MANAGEMENT** - **Acute mania:** Lithium, valproate, or an atypical antipsychotic (olanzapine, quetiapine, risperidone, aripiprazole). Use an antipsychotic for severe agitation or psychosis. Benzodiazepines are adjunctive for agitation/sleep. ECT is effective for refractory or severe mania, and for severe depression, catatonia, or pregnancy. - **Maintenance:** Lithium (gold standard; reduces suicide risk), valproate, lamotrigine (best for preventing depressive episodes), or an atypical antipsychotic. - **Bipolar depression:** Quetiapine, lurasidone, lamotrigine, or lithium. Avoid antidepressant monotherapy because of the risk of manic switch.

**KEY DRUG POINTS** - **Lithium:** - *Mechanism:* inhibits inositol monophosphatase/GSK-3. - *Narrow therapeutic index* (0.6–1.2 mEq/L). Toxicity causes coarse tremor, confusion, ataxia, seizures, and arrhythmias. - *Adverse effects (LiTHIUM):* nephrogenic diabetes insipidus (Li blocks ADH action), hypothyroidism, Ebstein anomaly (teratogen), tremor, and weight gain. It can also cause leukocytosis and T-wave flattening. - *Levels ↑ with* NSAIDs, ACE inhibitors, thiazides, and dehydration/low sodium. - *Monitoring:* renal function, thyroid function, calcium, and lithium level. - **Valproate:** Hepatotoxicity, pancreatitis, thrombocytopenia, neural tube defects, tremor, and weight gain. - **Carbamazepine:** SIADH/hyponatremia, agranulocytosis/aplastic anemia, CYP450 induction, and SJS/TEN (HLA-B*1502 in Asian patients). - **Lamotrigine:** Stevens-Johnson syndrome (titrate slowly; risk is higher with valproate coadministration). - **Atypical antipsychotics:** Metabolic syndrome, QT prolongation, and EPS (less common than with typical agents).

**BOARD PEARLS** - Mania with psychosis or hospitalization = bipolar I, regardless of duration. - Bipolar II requires NO manic episode, so any mania makes it bipolar I. - A depressed patient with a family history of bipolar disorder, or one who becomes manic on an SSRI, should be re-evaluated for bipolar disorder. - Always screen for medical and substance causes before diagnosis. - Lithium is contraindicated or used with extreme caution in significant renal disease, and in the first trimester because of Ebstein anomaly.