Restarting Lithium After One Week Interruption: Dosing Recommendations
A patient who missed lithium 800mg daily for one week should restart at the full previous dose of 800mg, not a reduced dose of 400mg, because lithium is completely eliminated within 7-10 days and the patient is essentially starting fresh without risk of accumulation. 1
Evidence-Based Rationale for Full Dose Restart
Lithium has an elimination half-life of 18-36 hours, requiring approximately 5-7 half-lives (roughly 7-10 days) to achieve steady state and equally to be completely eliminated from the body. 2, 1 After one week without lithium, the patient has essentially zero circulating lithium, making this equivalent to a new initiation rather than a dose adjustment scenario. 1
Monte Carlo simulation studies specifically examining missed lithium doses demonstrate that for patients with normal renal function, replacement with the regular full dose is the most appropriate strategy. 3 Starting at half the previous therapeutic dose (400mg instead of 800mg) would create an unnecessary delay in achieving therapeutic levels and leave the patient undertreated for an extended period. 3
Critical Safety Considerations
When Reduced Dosing IS Appropriate
The only scenario where reduced restart dosing is recommended is in patients with renal impairment (creatinine clearance <50 mL/min), where partial dose replacement appears most suitable to avoid toxicity. 4, 3 In these patients, creatinine clearance <50 mL/min is a significant predictor of lithium toxicity even at standard doses. 4
Mandatory Pre-Restart Assessment
Before restarting lithium at any dose, verify: 5, 2
- Current renal function (BUN, creatinine, eGFR) - particularly critical if the patient has developed any intercurrent illness during the week off lithium 6
- Electrolyte status - especially if the patient experienced dehydration or illness during the interruption 2
- Current medications - NSAIDs, ACE inhibitors, ARBs, thiazide diuretics all significantly increase lithium toxicity risk 7, 6, 8
Recommended Restart Protocol
For Patients with Normal Renal Function (eGFR ≥60 mL/min/1.73 m²)
Resume lithium 800mg daily immediately (same schedule as before - either once daily evening dose or divided twice daily). 1, 3
Check lithium level 5-7 days after restart to confirm achievement of steady state and therapeutic range (0.6-1.2 mEq/L for maintenance). 2, 1 Do not wait beyond 7-8 days to check levels, as steady state should be achieved and dose adjustments can be made at that point. 2
For Patients with Renal Impairment (eGFR <60 mL/min/1.73 m²)
Consider starting at 400mg daily with more frequent monitoring, as these patients have considerably reduced lithium clearance. 6, 3 If eGFR <30 mL/min/1.73 m², increase monitoring frequency to monthly and consider whether continuing lithium is appropriate given the risk-benefit profile. 2
Common Pitfalls to Avoid
Never assume that restarting at a lower dose is "safer" in patients with normal renal function - this only delays therapeutic benefit without reducing toxicity risk, since the patient has no residual lithium after one week. 1, 3
Do not restart lithium without assessing renal function first - even if the patient had normal function previously, intercurrent illness during the week off could have changed this. 4 Not overdose-related lithium toxicity occurs more frequently in patients with declining renal function who continue standard doses. 4
Avoid restarting lithium if the patient is currently taking NSAIDs, has started thiazide diuretics, or has developed acute illness - these dramatically increase toxicity risk and require dose adjustment or temporary discontinuation. 7, 6, 8
Monitoring After Restart
Check lithium level at 5-7 days post-restart (12 hours after last dose for twice-daily dosing, or 24 hours after dose for once-daily evening dosing). 2, 1
Resume standard maintenance monitoring schedule (lithium level, renal function, thyroid function every 3-6 months) once therapeutic levels are confirmed. 5, 2
Educate the patient on signs of lithium toxicity (fine tremor, nausea, diarrhea initially; coarse tremor, confusion, ataxia requiring immediate medical attention) since the restart period carries higher risk if renal function has changed. 5