Lithium (Lithobid)
Mood stabilizer • Last reviewed 2025-09-23
General information
Lithium is a monovalent cation and classic mood stabilizer approved for maintenance treatment of bipolar disorder and acute manic episodes. It remains the gold standard for relapse prevention, suicide risk reduction, and augmentation in treatment-resistant depression. Lithium carbonate and lithium citrate preparations have been in psychiatric use since the 1970s.
Formulations include immediate-release tablets/capsules (150, 300, 600 mg), extended-release tablets (300, 450 mg), and oral solution (8 mEq/5 mL). Dosing is individualized based on serum concentrations, renal function, and clinical response. Typical maintenance doses range from 900 to 1,200 mg/day divided twice or three times daily; some patients benefit from once-daily ER dosing to reduce renal adverse effects.
Lithium’s mechanism is multifactorial: it modulates second messenger systems (inositol monophosphatase, glycogen synthase kinase-3), influences circadian rhythms, and alters neurotransmitter release (serotonin, dopamine, glutamate). Neuroprotective effects may contribute to long-term benefits and suicide risk reduction.
The drug is renally eliminated with minimal metabolism. Serum half-life averages 18-36 hours in adults but may reach 40-50 hours in the elderly. Steady state occurs after 5 days. Lithium has a narrow therapeutic index requiring routine monitoring of serum levels and renal/thyroid function.
Dosing & administration
Acute mania: start 300 mg two to three times daily; adjust every 3-5 days to achieve serum levels 0.8-1.2 mEq/L.
Maintenance: target serum 0.6-1.0 mEq/L; consider 0.4-0.6 mEq/L for older adults or long-term prophylaxis if tolerated.
Switching to once-daily ER: give total daily dose at bedtime; check 12-hour trough levels after 5 days.
Dose adjustments required with changes in renal function, hydration status, or interacting medications.
Monitoring targets
- Baseline labs
- BMP, TSH, pregnancy test (if applicable), CBC, weight, ECG in patients >40 or with cardiac disease.
- Serum lithium
- Check 5 days after initiation or dose change; then every 3 months in maintenance.
- Renal function
- Every 3-6 months; more frequently if eGFR <60 mL/min.
- Thyroid function
- TSH every 6-12 months.
Mechanism of action
Lithium inhibits inositol monophosphatase and attenuates phosphatidylinositol signaling, reducing excitatory neurotransmission.
It inhibits glycogen synthase kinase-3 beta, affecting circadian rhythms, neuroplasticity, and gene expression, which may underlie mood-stabilizing and anti-suicidal effects.
- No direct receptor binding; acts on intracellular signaling pathways.
- Reduces dopamine neurotransmission; enhances serotonergic activity.
- Modulates NMDA receptor-mediated glutamate transmission.
Metabolism & pharmacokinetics
Lithium is rapidly absorbed (peak 1-3 hours IR, 4-6 hours ER) and widely distributed with volume of distribution approximating total body water.
Renal excretion mirrors sodium handling; half-life increases with age or renal impairment. Conditions that reduce renal perfusion (dehydration, NSAIDs) increase lithium levels.
- Tmax
- IR 1-3 h; ER 4-6 h
- Half-life
- 18-36 h (longer in elderly)
- Therapeutic trough
- 0.6-1.2 mEq/L
Drug interactions
ACE inhibitors, ARBs, and thiazide diuretics reduce lithium clearance, leading to toxicity.
NSAIDs decrease renal perfusion and increase serum lithium; avoid or monitor closely.
Caffeine and high sodium intake can lower lithium levels; abrupt changes cause instability.
| Mechanism | Agents / factors | Management |
|---|---|---|
| Reduced renal clearance | Thiazides, ACE inhibitors, ARBs | Reduce lithium dose and monitor levels within 5 days. |
| Renal perfusion decrease | NSAIDs, COX-2 inhibitors | Avoid or monitor lithium level within 3-5 days of initiation. |
| Neurotoxicity risk | Antipsychotics, carbamazepine | Monitor for encephalopathy, tremor; use lowest effective doses. |
Monitoring & safety checks
Serum lithium level
5 days after dose change, then every 3 months • Maintain therapeutic window and detect toxicity.
Renal function (BUN, creatinine, eGFR)
Baseline, 3 months, then every 6 months • Lithium can reduce GFR over time.
Thyroid function (TSH, free T4)
Baseline then every 6-12 months • Risk of hypothyroidism.
Calcium/Parathyroid
Annually • Lithium-induced hyperparathyroidism may cause hypercalcemia.
Educate about toxicity symptoms (coarse tremor, confusion, diarrhea) and importance of hydration.
Advise consistent salt intake and caution with dehydration (illness, heat).
Discontinuation guidance
Taper slowly over at least 4 weeks to reduce relapse risk; abrupt discontinuation increases relapse rates fivefold.
Monitor mood closely during taper and for 3 months after cessation.
Special populations
Pregnancy: associated with small increased risk of cardiac malformations (Ebstein anomaly); consider lowest effective dose and frequent monitoring; avoid in first trimester if alternatives available.
Older adults: lower therapeutic range (0.4-0.8 mEq/L) and once-daily dosing reduce polyuria and tremor.
Renal impairment: avoid initiation if eGFR <45 mL/min; if continuing, use lower doses and frequent monitoring.
Adverse effects
Common: fine tremor, polyuria/polydipsia, weight gain, nausea, cognitive dulling.
Chronic: nephrogenic diabetes insipidus, hypothyroidism, hyperparathyroidism.
Severe toxicity (>1.5 mEq/L): coarse tremor, ataxia, confusion, seizures, arrhythmias; requires urgent management.
References
- Lithobid (lithium carbonate) prescribing information — AbbVie (2023)
- CANMAT/ISBD guidelines on lithium use in bipolar disorder — Bipolar Disorders (2021) DOI: 10.1111/bdi.13135
- The science and practice of lithium therapy — International Journal of Bipolar Disorders (2017) DOI: 10.1186/s40345-017-0100-3
Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.