A patient on lithium extended‑release 300 mg daily with a sub‑therapeutic serum level—what is the appropriate next dose increase and monitoring plan?

Lithium ER 300 mg Dose Escalation

For a patient on lithium ER 300 mg daily with subtherapeutic levels, increase to 600 mg daily (300 mg twice daily) and check serum lithium level in 5-7 days after steady state is achieved. 1

Initial Dose Adjustment Strategy

• The FDA-approved dosing for acute treatment typically starts at 300 mg three times daily (900 mg total), with 300 mg daily representing an extremely low starting dose that produces levels of only 0.2-0.6 mEq/L 2
• Increase the dose to 600 mg daily (300 mg twice daily with extended-release formulation) as the next logical step, which remains conservative while moving toward therapeutic range 1
• For acute mania, target serum lithium levels of 1.0-1.5 mEq/L are required, while maintenance therapy targets 0.6-1.2 mEq/L 1

Monitoring Timeline After Dose Increase

• Check serum lithium level 5-7 days after the dose increase, as lithium requires 7-8 days (approximately 5-7 half-lives) to reach steady-state serum concentrations regardless of dosing schedule 2
• During the acute treatment phase, serum levels should be checked twice per week until both serum level and clinical condition stabilize 2, 3
• Blood samples must be drawn 8-12 hours after the previous dose when lithium concentrations are relatively stable 1

Subsequent Dose Titration

• If the level remains subtherapeutic after reaching 600 mg daily, increase to 900 mg daily (300 mg three times daily), which is the standard FDA-approved dosing for acute treatment 1
• Each dose increment should be followed by a 5-7 day waiting period before checking levels to allow steady state to be achieved 2
• Continue twice-weekly monitoring during dose escalation until therapeutic levels and clinical stability are achieved 2, 3

Concurrent Laboratory Monitoring

• Check renal function (BUN, creatinine, eGFR) and electrolytes 2-4 weeks after starting lithium or after dose adjustments, as the greatest changes in renal function biomarkers occur during initial treatment and dose escalation 2
• Monitor thyroid function (TSH, free T4) every 3-6 months once stable, as hypothyroidism develops in approximately 20-30% of patients on long-term lithium 2
• Increase monitoring frequency to every 1-2 weeks if there are changes in renal function, addition of interacting medications (NSAIDs, ACE inhibitors, ARBs, thiazide diuretics), or significant weight changes 2

Critical Safety Considerations

• Avoid concomitant NSAIDs, which significantly increase lithium levels and toxicity risk 2, 3
• Patients with eGFR <60 mL/min/1.73 m² require more frequent monitoring, and those with eGFR <30 mL/min/1.73 m² should be monitored at least monthly 2
• Early signs of toxicity include tremor, nausea, diarrhea, and polyuria-polydipsia—educate patients to report these symptoms immediately 4, 3

Special Population Adjustments

• Elderly patients often respond to reduced dosages and may exhibit toxicity at serum levels ordinarily tolerated by younger patients 1
• For patients over 60 years, the usual maintenance dose is 15-20 mmol (550-740 mg) daily, lower than younger adults 5
• Women under 60 years are at higher risk for thyroid dysfunction and warrant more frequent monitoring 2