How to Prescribe Lithium for Bipolar I Disorder
Initial Patient Assessment and Baseline Testing
Before initiating lithium, obtain comprehensive baseline laboratory studies including complete blood count, thyroid function tests (TSH, free T4), urinalysis, blood urea nitrogen, creatinine, serum calcium, and pregnancy test in females of childbearing age 1, 2, 3. Lithium should only be initiated in settings with personnel and facilities for close clinical and laboratory monitoring 4.
Dosing Strategy for Acute Mania
For acute mania, start lithium carbonate 600 mg three times daily (1800 mg/day total) in adults, targeting serum levels of 1.0-1.2 mEq/L 3. The FDA-approved dosing for acute mania typically produces effective serum lithium levels between 1.0 and 1.5 mEq/L 3. Response rates for acute mania range from 38-62%, with lithium demonstrating superiority over placebo (OR 2.13,95% CI 1.73-2.63) 5, 6.
Dosing Adjustments
- Elderly patients require reduced dosing and may exhibit toxicity at levels ordinarily tolerated by younger adults 3
- Individual patients may respond at lower concentrations (<0.8 mmol/L), though response likelihood increases with higher serum levels 7
- Dosage must be individualized according to serum levels and clinical response 3
Therapeutic Drug Monitoring Protocol
Draw serum lithium levels twice per week during the acute phase until levels and clinical condition stabilize 3, 8. Blood samples must be drawn 8-12 hours after the previous dose (trough levels) when lithium concentrations are relatively stable 3.
Target Therapeutic Ranges
- Acute mania: 0.8-1.2 mEq/L (some sources cite up to 1.5 mEq/L) 2, 3, 7
- Maintenance therapy: 0.6-1.0 mEq/L 3, 8
- Maintaining higher concentrations (0.8-1.0 mmol/L) improves prophylactic efficacy, though individual patients may respond at lower levels 7
Transition to Maintenance Therapy
Once acute symptoms stabilize, reduce to maintenance dosing of 300 mg three to four times daily (900-1200 mg/day), targeting serum levels of 0.6-1.0 mEq/L 3. The desirable maintenance range is 0.6-1.2 mEq/L, with typical dosing of 300 mg TID or QID 3.
Ongoing Monitoring Requirements
Monitor lithium levels, renal function (BUN, creatinine), thyroid function (TSH), and urinalysis every 3-6 months during maintenance therapy 1, 2, 4. During uncomplicated maintenance therapy, serum lithium levels should be monitored at least every two months 3.
Duration of Treatment
Continue maintenance therapy for at least 12-24 months after mood stabilization 2, 4. Lithium demonstrates superior evidence for long-term prophylaxis compared to other mood stabilizers, preventing both manic and depressive episodes 2, 8. Withdrawal of maintenance lithium dramatically increases relapse risk, with >90% of noncompliant adolescents relapsing versus 37.5% of compliant patients 2, 4.
Combination Therapy Considerations
For severe or treatment-resistant mania, combine lithium with an atypical antipsychotic (aripiprazole, risperidone, olanzapine, or quetiapine) 2, 4. Combination therapy with lithium plus valproate is superior to valproate monotherapy for relapse prevention (HR 0.59,95% CI 0.42-0.83) 9. Quetiapine plus valproate is more effective than valproate alone for adolescent mania 2, 4.
Common Adverse Effects and Management
Lithium commonly causes tremor (OR 3.25 vs placebo) and somnolence (OR 2.28 vs placebo) 5. Patients abnormally sensitive to lithium may exhibit toxic signs at serum levels of 1.0-1.5 mEq/L 3. Educate patients on early signs of lithium toxicity including fine tremor, nausea, and diarrhea, with immediate medical attention required for coarse tremor, confusion, or ataxia 2.
Critical Safety Considerations
- Never discontinue lithium abruptly—taper gradually over 2-4 weeks minimum to prevent rebound mania 2
- Lithium overdoses can be lethal; implement strict medication supervision in patients with suicide history 2
- Maintain adequate hydration and salt intake, as dehydration increases lithium levels 2
- Total reliance must not be placed on serum levels alone—accurate evaluation requires both clinical and laboratory analysis 3
Special Populations
Lithium is FDA-approved for patients age 12 and older 2, 4. For elderly patients or those with Alzheimer's disease, lower target ranges of 0.2-0.6 mEq/L (achieved with 150-300 mg daily) may be adequate 2.
Unique Anti-Suicide Benefits
Lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties 2, 8. This makes lithium particularly valuable for high-risk patients with bipolar disorder 2.