Lithium: Uses, Dosage, Side Effects, Monitoring, and What to Expect

Lithium carbonate / lithium citrate (brand name: Lithobid, Eskalith) is a mood stabilizer (alkali metal). Lithium's mechanism remains incompletely understood despite decades of research. Known effects include inhibition of glycogen synthase kinase-3 (GSK-3), which affects neuroplasticity and neuroprotection; modulation of inositol signaling pathways; effects on circadian rhythm regulation; and enhancement of serotonergic neurotransmission. Lithium is the only psychiatric medication with robust evidence for reducing suicide risk independent of its mood-stabilizing effects.

• Bipolar I Disorder (acute mania and maintenance)
• Bipolar Depression (acute, though less effective than for mania)

Common off-label uses:

• Augmentation of antidepressants in treatment-resistant depression
• Schizoaffective disorder
• Cluster headache prophylaxis
• Aggression/impulsivity

Target serum levels: 0.6-1.0 mEq/L for maintenance, 0.8-1.2 mEq/L for acute mania. Typical doses: 600-1800 mg/day divided into 2-3 doses (immediate release) or once daily (extended release). Dosing is guided by blood levels, not milligrams. Narrow therapeutic index — levels above 1.5 mEq/L are toxic.

Antimanic effects begin within 5-7 days. Full mood stabilization takes 1-3 weeks. Acute mania often requires bridging with an antipsychotic.

• Fine hand tremor
• Increased thirst and urination (polyuria/polydipsia)
• Weight gain
• Nausea and GI upset
• Cognitive dulling
• Hypothyroidism (up to 20% long-term)
• Acne
• Hair changes

• Lithium toxicity (levels >1.5 mEq/L) — symptoms include coarse tremor, confusion, vomiting, ataxia, seizures; can be fatal
• Nephrogenic diabetes insipidus
• Chronic kidney disease (long-term risk with chronic use)
• Cardiac conduction abnormalities (including sick sinus syndrome)
• Ebstein's anomaly in first trimester pregnancy exposure (rare)
• Hypothyroidism requiring thyroid supplementation

NSAIDs, ACE inhibitors, and ARBs increase lithium levels (dangerous). Thiazide diuretics increase levels. Dehydration, low-sodium diets, and illness increase levels. Caffeine and osmotic diuretics decrease levels. Any change in hydration status, diet, or medications warrants level checking.

Known teratogen — associated with Ebstein's anomaly (cardiac malformation), though the absolute risk is lower than previously thought (~0.1-0.2% vs. 0.005% baseline). Contraindicated in first trimester if possible. If continued, high-resolution fetal echocardiography at 16-20 weeks is recommended. Lithium levels fluctuate dramatically during pregnancy and postpartum.

Taper over 2-4 weeks minimum. Abrupt discontinuation significantly increases relapse risk — some studies suggest rebound mania occurs within weeks. Gradual discontinuation over months is associated with better outcomes.