Restarting Lithium After One Week Interruption
Do not restart lithium at the full 800mg dose after a one-week interruption—this requires gradual retitration to avoid toxicity and ensure therapeutic monitoring, as abrupt discontinuation followed by full-dose restart increases the risk of both rebound mania and neurotoxicity. 1, 2, 3
Immediate Clinical Assessment Required
Before restarting lithium, verify the following parameters:
- Check current renal function (BUN, creatinine, GFR) as kidney function directly affects lithium clearance and dosing requirements 2, 4
- Assess hydration status and ensure adequate fluid intake before reinitiating therapy 5
- Review any new medications started during the gap, particularly NSAIDs, ACE inhibitors, or diuretics, which significantly alter lithium levels 5, 6
- Evaluate for signs of relapse (manic or depressive symptoms) that may have emerged during the one-week gap 5, 7
Retitration Protocol
The patient should NOT simply resume 800mg. Instead, follow this approach:
- Start at a reduced dose (typically 50-75% of the previous maintenance dose, so approximately 400-600mg) and retitrate based on clinical response and serum levels 2, 4
- Obtain lithium levels twice weekly during the acute retitration phase until stabilized 2
- Target therapeutic range of 0.6-1.2 mEq/L for acute treatment, with levels drawn 12 hours post-dose 2
- Gradually increase to the previous maintenance dose over 1-2 weeks while monitoring for both efficacy and toxicity 2
The rationale for gradual retitration is that even a one-week gap represents a significant interruption in steady-state pharmacokinetics, and lithium's narrow therapeutic index (toxicity begins at 1.5 mEq/L) makes full-dose restart dangerous 4, 3.
Critical Risk: Rebound Mania
Missing lithium for even a few days significantly increases the risk of early manic recurrence, with the highest risk occurring in the first weeks after discontinuation 7. This rebound effect exceeds the natural relapse rate of bipolar disorder and can occur even with brief interruptions 7. The patient should be:
- Monitored closely for emerging manic symptoms during retitration 5, 7
- Counseled about the increased relapse risk associated with the interruption 2, 7
- Considered for bridging therapy with an atypical antipsychotic if manic symptoms are emerging 5
Monitoring During Retitration
Implement the following monitoring schedule:
- Lithium levels: Check 5-7 days after each dose adjustment, then twice weekly until stable 2
- Renal function: Repeat within 1-2 weeks of restarting, then every 3-6 months once stable 2
- Thyroid function: Check within the first month, as lithium-induced hypothyroidism can present with mood symptoms 2
- Clinical toxicity signs: Monitor for tremor, confusion, ataxia, or slurred speech—these can occur even at "therapeutic" levels in some patients 3, 8
Special Considerations
If the patient has reduced kidney function (GFR <60 mL/min/1.73 m²), the restart dose should be even lower (approximately 50% of previous dose) with more frequent monitoring 4. Elderly patients similarly require lower starting doses and closer observation 4.
If the gap was due to intentional discontinuation or non-adherence, address the underlying cause before restarting. Consider whether long-acting injectable antipsychotics might be more appropriate for maintenance therapy in patients with adherence challenges 5.
Common Pitfall to Avoid
Never restart at full dose simply because the patient was previously stable on that dose. The one-week interruption has eliminated steady-state levels, and the patient's clinical status may have changed during the gap (hydration, renal function, concurrent medications) 4, 3, 6. Treating the patient as a "restart" rather than a "continuation" is the safest approach.