What is the recommended dosing for lithium (lithium carbonate) therapy?

Lithium Dosing Recommendations

Initial Dosing for Acute Mania

For acute mania, start lithium carbonate at 600 mg three times daily (1800 mg/day total), targeting serum levels of 1.0-1.5 mEq/L, with dose adjustments based on twice-weekly serum level monitoring until stabilization. 1

• The FDA-approved starting regimen is 600 mg three times daily, which typically produces effective serum lithium levels between 1.0-1.5 mEq/L 1
• For elderly patients (>60 years), reduce the starting dose to 150 mg/day due to increased sensitivity and reduced clearance 2
• Initial dosing for younger adults (<40 years) can range from 450-900 mg daily (12-24 mmol), adjusted based on age and body weight 3

Maintenance Dosing for Long-Term Control

For maintenance therapy, use 300 mg three to four times daily (900-1200 mg/day total), targeting serum levels of 0.6-1.2 mEq/L, with the optimal range being 0.8-1.0 mEq/L for maximum efficacy. 1, 4

• The desirable maintenance serum lithium level is 0.6-1.2 mEq/L, though levels of 0.8-1.0 mEq/L are more effective at preventing relapse 1, 4
• Patients maintained at 0.8-1.0 mEq/L have a 2.6 times lower risk of relapse compared to those at 0.4-0.6 mEq/L, despite experiencing more side effects 4
• Lower levels (0.2-0.6 mEq/L) may be adequate when lithium is used to augment antidepressants 2

Age-Based Maintenance Dosing

• Patients <40 years: 925-1300 mg daily (25-35 mmol) 3
• Patients 40-60 years: 740-925 mg daily (20-25 mmol) 3
• Patients >60 years: 550-740 mg daily (15-20 mmol) 3

Dosing Schedule: Once Daily vs. Multiple Daily Doses

Administer lithium as a single evening dose or twice daily rather than three times daily to improve tolerability and compliance. 3, 5

• Once-daily dosing produces similar efficacy to twice-daily dosing but with significantly lower urinary frequency and better compliance 5
• Twice-daily dosing requires higher total daily doses and produces lower serum lithium levels compared to once-daily administration 5
• With sustained-release formulations, twice-daily dosing is well-established, though single evening dosing is increasingly recommended 3
• Sustained-release preparations reach peak plasma concentrations at 4-5 hours (versus 1-2 hours for standard-release), with 30-50% reductions in peak levels 3

Renal Impairment Dosing Adjustments

For patients with GFR <60 mL/min/1.73 m², use lower doses with more frequent monitoring; reduce the dose by 50% when GFR <30 mL/min/1.73 m². 2

• Renal insufficiency substantially reduces lithium clearance and is considered a relative contraindication, especially with sodium-restricted diets 2, 3
• Patients with reduced kidney function require monitoring more frequently than the standard 3-6 month interval 6
• Weight, creatinine clearance, and total daily dose all affect lithium clearance 7
• For patients weighing >100 kg with renal insufficiency, use 500 mg daily rather than 750 mg to achieve target trough concentrations 7

Monitoring Schedule

Acute Phase Monitoring

Check serum lithium levels twice per week during acute treatment until both serum levels and clinical condition stabilize. 1, 2

• Draw blood samples 8-12 hours after the previous dose (immediately before the next dose) when concentrations are relatively stable 1
• For once-daily administration, the 24-hour serum concentration should serve as the control value 3

Maintenance Phase Monitoring

Monitor serum lithium levels every 3-6 months during stable maintenance therapy. 6

• In uncomplicated cases during remission, monitor at least every two months 1
• Increase monitoring frequency to 1-2 weeks after dose adjustments, addition of interacting medications, changes in renal function, or significant weight changes 6

Baseline and Ongoing Laboratory Monitoring

Before initiating lithium, obtain complete blood count, thyroid function tests (TSH, free T4), renal function (BUN, creatinine, GFR), serum electrolytes including calcium, and urinalysis. 2

• Monitor thyroid function tests, weight, and blood pressure annually during maintenance therapy 6
• Assess for contraindications including significant renal impairment, cardiovascular disease, severe dehydration, and sodium depletion 2

Critical Safety Considerations

Lithium toxicity occurs at doses close to therapeutic levels, with toxicity risk beginning at 1.5 mEq/L and serious toxicity at >2.0 mEq/L. 2

• Patients abnormally sensitive to lithium may exhibit toxic signs at serum levels of 1.0-1.5 mEq/L 1
• Avoid concomitant NSAIDs as they increase lithium levels and toxicity risk 2
• Maintain adequate hydration, especially during intercurrent illness 2
• During pregnancy, lithium clearance increases by 30-50% in the last months, requiring dose adjustments 3
• Lithium use in early pregnancy is associated with increased cardiovascular anomalies, particularly tricuspid valve abnormalities 8