Restarting Lithium After Abrupt Discontinuation
Do not restart lithium at the previous dose after abrupt discontinuation—this creates significant risk of toxicity, especially with any degree of renal impairment. 1
Critical Safety Considerations
The FDA label explicitly warns that lithium should generally not be given to patients with significant renal disease, as the risk of lithium toxicity is very high in such patients 1. Even if renal function was normal before discontinuation, the abrupt cessation itself may have altered fluid balance and renal handling of lithium 1.
Lithium toxicity is closely related to serum lithium levels and can occur at doses close to therapeutic levels, making the restart period particularly dangerous 1.
Evidence-Based Restart Protocol
If Lithium Was Discontinued for ≤5 Days
- Resume at the previous maintenance dose, as the pharmacodynamic stress of discontinuation has not fully developed 2
- Check lithium level within 3-5 days of restart 2
If Lithium Was Discontinued for >5 Days
- Restart with full titration schedule rather than resuming the previous dose to minimize risk of serious adverse effects 2
- Begin at 300mg twice daily (or 600mg extended-release once daily) 2
- Titrate gradually over 2-4 weeks to reach therapeutic levels of 0.8-1.2 mEq/L 2
- Monitor lithium levels, renal function (BUN, creatinine), and thyroid function at baseline and after reaching steady state 3, 2
Special Precautions for Patients with Renal Concerns
- Obtain baseline renal function tests (BUN, creatinine, urinalysis) before any restart 3
- If creatinine is elevated or creatinine clearance is reduced, lithium may require hospitalization for careful monitoring with daily serum lithium determinations 1
- Use lower doses than previously tolerated if any renal impairment is present 1
Why Gradual Restart Matters
The abrupt discontinuation itself creates a pharmacodynamic stress that dramatically increases relapse risk—particularly for mania 4, 5. However, restarting at full dose after a gap risks toxicity because:
- Fluid balance may have changed during the off-lithium period 1
- Renal concentrating ability may be altered 1
- The patient may be dehydrated or sodium-depleted 1
- Concurrent medications (NSAIDs, ACE inhibitors, diuretics) may have been started 4
Monitoring During Restart
- Check lithium level 5 days after each dose adjustment 2
- Monitor for early signs of toxicity: tremor, confusion, ataxia, polyuria 1
- Assess renal function (creatinine) and thyroid function (TSH) every 3-6 months once stable 3, 2
- Counsel patient extensively about maintaining adequate fluid intake and avoiding drug interactions 4
Common Pitfall to Avoid
Never assume that because a patient was stable on a certain dose before, that same dose is safe to restart immediately after discontinuation. The physiologic changes during the off-lithium period, combined with the narrow therapeutic index of lithium, make this approach dangerous 1.