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Bipolar disorder - Management
What are the drug interactions of lithium?
- Because of lithium's narrow therapeutic index, interactions with other drugs can be very important. The most commonly encountered interactions are with:
- Diuretics: thiazide diuretics can increase serum lithium levels by reducing clearance of lithium. People who are stabilized on lithium and begin taking thiazide diuretics are at significant risk of developing lithium toxicity. Toxic lithium concentrations may be seen within 3–5 days. Loop diuretics also cause lithium retention but are less likely to result in lithium toxicity.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase serum lithium levels by up to 40%. The mechanism of this interaction is thought to be related to the effects of NSAIDs on fluid balance. This is particularly important if NSAIDs are added to a long-standing prescription of lithium.
- Haloperidol: although severe neurotoxicity has been reported with this combination, if lithium levels are maintained in the therapeutic range (0.6–1.0 mmol/L) and the haloperidol dose is not increased rapidly above the recommended maximum, the chance of inducing a toxic state is very low.
- Carbamazepine in combination with lithium has been reported to cause neurotoxic reactions. Higher (greater than 1 mmol/L) plasma lithium levels were involved than are now thought acceptable, so a neurotoxic reaction to lithium alone was a risk factor. Carbamazepine and lithium may therefore be usefully co-prescribed.
- Antidepressants with a serotonergic action (such as selective serotonin reuptake inhibitors, tricyclic antidepressants, venlafaxine, duloxetine) have rarely been linked to an increased incidence of central nervous system toxicity when used with lithium. The mechanism of this interaction is not well understood. Prescribers should check lithium levels soon after starting treatment with a serotonergic antidepressant, although there are some reports of neurotoxic reactions in the absence of raised lithium levels.
- ACE inhibitors decrease the excretion of lithium. They can also precipitate renal failure. If these two drugs are prescribed together, extra care is required in monitoring both serum creatinine and lithium.
[Sweetman, 2005; ABPI Medicines Compendium, 2006a; Taylor et al, 2007]
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