Bipolar Disorder — Mania, Mood Stabilizers & Lithium

Creator: Progress Note
Published: 2026-07-22
Keywords: bipolar disorder treatment mood stabilizers, bipolar manic episode DSM, lithium vs valproate bipolar, bipolar disorder USMLE, bipolar types 1 vs 2

The 60-second version

Mania (Bipolar I): ≥7 days + DIGFAST ≥3 symptoms; hypomania (Bipolar II) = 4 days, no impairment
Lithium: best long-term maintenance + anti-suicidal; narrow window; NSAID/ACEi increase toxicity
Valproate: mixed episodes + rapid cycling; TERATOGENIC (neural tube defects — avoid in pregnancy)
Lamotrigine: best for bipolar depression prevention; risk of Stevens-Johnson (titrate slowly)
Never give antidepressant monotherapy in bipolar — can trigger mania or rapid cycling

DSM-5 Criteria and Bipolar Types

Manic episode: ≥7 days (or any duration if hospitalized) of elevated/expansive/irritable mood + increased goal-directed activity OR energy, PLUS ≥3 of DIGFAST: Distractibility, Impulsivity/reckless behavior, Grandiosity, Flight of ideas, Activity increase (goal-directed), Sleep decrease (decreased need, not insomnia), Talkativeness (pressured speech). Causes significant impairment; not due to substances or medical conditions (hyperthyroidism, stimulants, steroids can mimic mania). Hypomanic episode: same criteria but only 4 days; no hospitalization; does NOT cause significant impairment. Bipolar I: at least one manic episode (depressive episodes common but not required for diagnosis). Bipolar II: at least one hypomanic episode + at least one MDD episode; NO full manic episodes. Cyclothymia: 2 years of hypomanic + depressive symptoms that never meet full criteria. Rapid cycling: ≥4 mood episodes per year (any combination); associated with hypothyroidism and antidepressant use.

Mood Stabilizers: Lithium vs Valproate vs Lamotrigine

Lithium: first-line for bipolar I, especially for mania prevention and long-term maintenance. Unique advantage: anti-suicidal effect (reduces suicide by 60–80% in bipolar disorder). Mechanism: multiple — inhibits inositol phosphatase + GSK-3beta. Toxicity (narrow therapeutic window 0.8–1.2 mEq/L): early: tremor, GI upset, polyuria (NDI), polydipsia, weight gain, hypothyroidism, acne. Toxic (>1.5–2.0 mEq/L): coarse tremor, confusion, ataxia, seizures, cardiac arrhythmias. Triggers for toxicity: NSAID use (reduces renal Li excretion), ACE inhibitors/ARBs, dehydration, sodium restriction, loop diuretics. Monitor: TFTs, renal function, serum levels. Contraindicated in pregnancy (Ebstein anomaly — fetal tricuspid valve malformation, lower risk than historical reports). Valproate: preferred for mixed episodes, rapid cycling, or acute mania. Better tolerated than lithium for many patients. Side effects: weight gain, tremor, alopecia, thrombocytopenia, hepatotoxicity (LFTs), pancreatitis, TERATOGENIC (neural tube defects — spina bifida; 1–2% risk; avoid in women of childbearing age; if used, ensure folate). Lamotrigine: best for bipolar depression maintenance and prevention of depressive episodes; less effective for mania. Risk: Stevens-Johnson syndrome / toxic epidermal necrolysis (especially with rapid dose titration or valproate combination — valproate doubles lamotrigine levels). Titrate slowly. Atypical antipsychotics: quetiapine (approved for bipolar depression and mania), aripiprazole, olanzapine (second-line — significant metabolic effects).

Antidepressants in Bipolar Disorder

Antidepressants (SSRIs, SNRIs) used WITHOUT mood stabilizers in bipolar disorder can: trigger manic switch (switch from depression to full mania), induce rapid cycling, increase mixed episodes. Rule: never prescribe antidepressant monotherapy for depression in a known bipolar patient — always pair with a mood stabilizer. Exception: bupropion has the lowest risk of triggering mania among antidepressants if needed. For bipolar depression (bipolar I): first-line is quetiapine or lithium/lamotrigine monotherapy — NOT antidepressants. Lurasidone + lithium/valproate is also approved. Key board question: a patient prescribed an SSRI who develops pressured speech, decreased sleep, and grandiosity has bipolar disorder with antidepressant-induced mania — stop SSRI, start mood stabilizer.

Test yourself

Quick check — 2 questions

1. A patient with bipolar disorder is started on valproate. Which lab monitoring is most important in the first 3 months?

2. A 28-year-old woman with a first episode of MDD is started on sertraline. After 6 weeks, she presents with decreased need for sleep (3 hours and feels rested), pressured speech, and plans to quit her job and start a business with no money. The next best step is:

Frequently asked questions

A patient on lithium develops coarse tremor, confusion, and diarrhea. Her lithium level is 2.4 mEq/L. What is the treatment?

Lithium level >2.0 mEq/L = severe lithium toxicity. Treatment: stop lithium immediately; IV normal saline to enhance renal lithium clearance (sodium competes with lithium for tubular reabsorption — sodium depletion causes lithium retention). For severe toxicity with neurological symptoms (seizures, severe confusion, arrhythmias) or level >4.0 mEq/L: hemodialysis (lithium is dialyzable — small molecule, no protein binding). Do NOT give sodium bicarbonate (raises Li reabsorption). NSAIDs are the most common cause of lithium toxicity in outpatients — they reduce prostaglandin-mediated renal blood flow and decrease lithium clearance.

How do you distinguish a manic episode from ADHD or stimulant intoxication?

Mania: episodic (defined onset), grandiosity (not typical of ADHD), decreased sleep need (not insomnia — patient feels rested on 3 hours), hypersexuality, reckless behavior with insight only partially retained. ADHD: chronic (not episodic), inattention is primary symptom, no grandiosity, no decreased sleep need. Stimulant (cocaine/amphetamine) intoxication: acute onset during use, resolves with drug clearance, tachycardia + hypertension + pupil dilation, urine tox screen positive. Secondary mania (medical): hyperthyroidism, CNS lesions (right frontal lobe), steroids, delirium — rule out with TFTs, BMP, imaging, and careful history.

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