BLACK BOX WARNING
- lithium toxicity can occur at doses close to therapeutic levels — facilities and clinician expertise for serum level monitoring required
lithium carbonate / lithium citrate
Brand: Lithobid, Eskalith
⚠ BBW Beers Criteria TDM Required Prototype Drug
Drug Class: mood stabilizer
Drug Family: mood stabilizer
Subclass: alkali metal ion
Organ Systems: cns
Mechanism of Action
Inhibits inositol monophosphatase (depleting inositol and reducing phosphoinositide signaling) and GSK-3 (affecting neuronal plasticity); also modulates neurotransmitter release and receptor sensitivity; mechanism of mood stabilization not fully established.
inositol monophosphataseglycogen synthase kinase-3 (GSK-3)
Indications
- bipolar disorder (acute mania — first-line)
- bipolar maintenance prophylaxis
- augmentation of antidepressants in treatment-resistant depression
- cluster headache prophylaxis
Contraindications
- severe renal impairment
- dehydration or sodium depletion
- concurrent diuretics and NSAIDs (relative)
- pregnancy (first trimester — Ebstein's anomaly risk)
Adverse Effects
Common
- fine tremor
- polyuria
- polydipsia
- weight gain
- cognitive dulling
- nausea
- diarrhea
- acne
Serious
- lithium toxicity (coarse tremor, confusion, ataxia, seizures, coma)
- nephrogenic diabetes insipidus
- hypothyroidism
- cardiac conduction abnormalities
- Ebstein's anomaly (first-trimester exposure)
Pharmacokinetics (ADME)
| Absorption | Complete oral absorption; distributed throughout total body water |
| Distribution | Not protein-bound; Vd ~0.7–1.0 L/kg; distributes like sodium; crosses BBB and placenta |
| Metabolism | Not metabolized; excreted unchanged |
| Excretion | Entirely renal; proximal tubule reabsorption competes with sodium — sodium depletion increases lithium reabsorption and toxicity risk |
| Half-life | 18–36 hours |
| Onset | 5–7 days for antimanic effect |
| Peak | 0.5–3 hours (immediate release); 4–12 hours (extended release) |
| Duration | 12–24 hours |
| Protein Binding | 0% |
| Vd | 0.7–1.0 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| NSAIDs and COX-2 inhibitors | reduce renal prostaglandin synthesis, decreasing lithium clearance by up to 20–25% | major |
| thiazide diuretics | sodium depletion increases proximal tubular lithium reabsorption; levels may increase 25–40% | major |
| ACE inhibitors / ARBs | reduce aldosterone, impairing lithium excretion; levels can double | major |
Nursing Considerations
- Therapeutic drug monitoring is mandatory: target serum trough level 0.8–1.2 mEq/L (acute mania) or 0.6–0.8 mEq/L (maintenance); toxic above 1.5 mEq/L — draw 12 hours after last dose
- Maintain consistent sodium intake and hydration; instruct patient to avoid dehydration, low-salt diets, excessive sweating, and OTC NSAIDs
- Lithium toxicity signs: coarse tremor, confusion, ataxia, nausea, vomiting (early); seizures, coma, cardiac arrhythmias (severe) — hold and notify provider immediately
- Monitor thyroid function (TSH) every 6–12 months; hypothyroidism occurs in ~30% of long-term users; monitor renal function annually (polyuria and nephrogenic DI are common)
Clinical Pearls
- Lithium is the only medication with level-1 evidence for antisuicidal effect in bipolar disorder — this unique benefit makes it irreplaceable despite its narrow therapeutic index
- The sodium-lithium competition in the proximal tubule explains the many drug interactions: anything that depletes sodium (diuretics, low-sodium diet, vomiting, diarrhea) will cause lithium retention and toxicity
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.