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

Once-Daily Lithium Dosing Regimen

For once-daily lithium dosing, administer the total daily dose as a single evening dose using sustained-release formulations, with target maintenance levels of 0.6-1.2 mEq/L measured 24 hours after the last dose. 1, 2, 3

Formulation Selection and Timing

• Use sustained-release preparations (extended-release) for once-daily dosing, as these formulations reduce peak plasma concentrations by 30-50% while maintaining therapeutic efficacy 2
• Administer the single daily dose in the evening to optimize compliance and minimize side effects 2
• Standard immediate-release formulations reach peak levels at 1-2 hours, while sustained-release forms peak at 4-5 hours, making the latter more suitable for once-daily administration 2

Initial Dosing Strategy

• Start with 450-900 mg daily (12-24 mmol) depending on age and body weight 2
• For elderly patients specifically, begin with lower doses of 150 mg/day due to increased sensitivity and reduced lithium clearance 4
• Typical maintenance doses by age group: 2
  • Age <40 years: 925-1300 mg daily (25-35 mmol)
  • Age 40-60 years: 740-925 mg daily (20-25 mmol)
  • Age >60 years: 550-740 mg daily (15-20 mmol)

Target Serum Levels and Monitoring Timing

Critical distinction for once-daily dosing: When using once-daily sustained-release lithium, draw serum levels at 24 hours post-dose, not the traditional 12 hours 3. This is essential because:

• Serum lithium levels at 12 hours are approximately 1.3 times higher than true trough levels at 24 hours in once-daily dosing 3
• Using the 12-hour standard for once-daily dosing will falsely elevate readings and may result in underdosing patients 3
• For sustained-release preparations, 90% of the dose is absorbed by 4 hours and 100% by 8 hours, but the 24-hour level represents the true trough for once-daily administration 5, 3

Target Therapeutic Ranges

• Maintenance therapy: 0.6-1.2 mEq/L (some sources favor 0.6-0.8 mEq/L) 1, 2
• Acute mania: 1.0-1.5 mEq/L 1
• Lithium augmentation of antidepressants: Lower levels of 0.2-0.6 mEq/L may be adequate 4, 6
• For sustained-release preparations specifically, maintain levels in the upper therapeutic range (0.8-1.0 mEq/L) rather than 0.6-0.8 mEq/L used for standard formulations 2

Monitoring Frequency

Acute phase: Check serum levels twice weekly until both levels and clinical condition stabilize 1, 4

Maintenance phase: Monitor every 3-6 months in stable patients 7

Increased monitoring required: 7

• 1-2 weeks after dose adjustments
• When adding interacting medications (especially NSAIDs, which must be avoided) 4, 6
• With changes in renal function
• After significant weight changes

Renal Function Considerations

• GFR 30-60 mL/min/1.73 m²: Use lower doses and increase monitoring frequency 4
• GFR <30 mL/min/1.73 m²: Reduce dose by 50% 4
• GFR <30 with serious intercurrent illness: Temporarily discontinue lithium 6
• Baseline and ongoing monitoring of renal function (BUN, creatinine, GFR) is mandatory 4, 7

Common Pitfalls to Avoid

• Do not use the 12-hour sampling time for once-daily dosing—this will overestimate true trough levels and lead to underdosing 3
• Never co-prescribe NSAIDs, as they decrease lithium clearance and increase toxicity risk 4, 6
• Toxicity begins at 1.5 mEq/L and becomes serious at >2.0 mEq/L, emphasizing the narrow therapeutic window 4
• Ensure adequate hydration, especially during intercurrent illness 4