What are the considerations for changing a patient's lithium (lithium) regimen from 300 mg twice daily (bid) to once daily?

Switching Lithium from Twice Daily to Once Daily Dosing

You can safely switch this patient from lithium 300 mg twice daily to 600 mg once daily in the evening, which maintains the same total daily dose while potentially improving tolerability and compliance. 1, 2

Rationale for Once-Daily Dosing

Once-daily lithium administration is a well-established, evidence-based approach that offers several advantages over divided dosing without compromising efficacy:

• The FDA label explicitly supports once-daily dosing for maintenance therapy, stating that "300 mg of lithium carbonate t.i.d. or q.i.d. will maintain" therapeutic levels, and modern practice increasingly favors single evening dosing 1
• Multiple randomized controlled trials demonstrate equivalent efficacy between once-daily and twice-daily schedules, with no significant differences in symptom recurrence or plasma lithium concentrations 2, 3
• Once-daily dosing significantly reduces urinary frequency and polyuria, which are common reasons for non-compliance—patients on twice-daily dosing experienced significantly higher urinary frequency (p=0.008 at Day 21, p=0.035 at Day 42) 2, 4
• Single daily dosing may reduce long-term renal damage risk and improves medication adherence 3, 5

Implementation Strategy

Switch directly to 600 mg once daily in the evening:

• Administer the full 600 mg dose as a single evening dose rather than splitting it 1, 6
• Evening dosing is preferred because it minimizes daytime side effects and allows for the recommended 12-hour post-dose blood draw timing in the morning 1, 6
• No dose titration is needed since the total daily dose remains unchanged at 600 mg 2

Critical Monitoring Requirements

Check serum lithium level 5-7 days after the switch:

• Draw blood 12 hours after the evening dose (i.e., the next morning before any dose) 1
• Target therapeutic range remains 0.6-1.2 mEq/L for maintenance therapy 1
• Once-daily dosing produces higher peak concentrations (occurring 1-2 hours post-dose for standard formulations) but equivalent trough levels and area under the curve 6

Monitor renal function and electrolytes within 2-4 weeks of the switch:

• Check GFR, creatinine, and electrolytes given lithium's nephrotoxic potential 7, 8
• Patients with GFR <60 mL/min/1.73 m² require more frequent monitoring 8

Common Pitfalls to Avoid

Do not split tablets to achieve once-daily dosing:

• Lithium has a narrow therapeutic index (toxicity begins at 1.5 mEq/L), making inconsistent dosing from improperly split tablets dangerous and therapeutic monitoring unreliable 9
• Use intact 600 mg tablets or two 300 mg tablets taken together 9

Warn the patient about transient post-dose effects:

• Single daily dosing causes brief, mild postabsorptive side effects (tremor, nausea) 1-2 hours after the dose, which is why evening dosing is preferred 6, 5
• These effects are transient and do not indicate toxicity if trough levels remain therapeutic 5

Counsel on hydration and medication interactions:

• Maintain adequate hydration, especially during intercurrent illness 8
• Avoid NSAIDs, which decrease lithium clearance and increase toxicity risk 7, 8
• Increase monitoring frequency if adding interacting medications or if renal function changes 8

Special Considerations

This patient's current dose (600 mg total daily) is appropriate for maintenance:

• The FDA label indicates 300 mg three to four times daily (900-1200 mg/day) for acute mania, but maintenance typically requires lower doses 1
• At 600 mg daily, this patient is likely in the maintenance phase with target levels of 0.6-1.2 mEq/L 1

If the patient were elderly or had renal impairment:

• Elderly patients often require lower doses and exhibit toxicity at levels tolerated by younger patients 1
• Patients with GFR <60 mL/min/1.73 m² need dose reduction and more frequent monitoring; GFR <30 mL/min/1.73 m² requires monthly monitoring if lithium is continued 8