CLINICAL RELEVANCE OF DRUG-INTERACTIONS WITH LITHIUM

Although lithium continues to be regarded as the treatment of choice f or bipolar disorders, the clinical use of this mood stabiliser is asso ciated with an extremely narrow therapeutic range. Relatively minor in creases in serum concentrations may induce serious adverse sequelae, a nd concentrations within the therapeutic range may result in toxic rea ctions. The safety of combining lithium with other medications, theref ore, is a major concern, and extensive clinical experience has served to identify several significant drug interactions. Lithium removal fro m the body is achieved almost exclusively via renal means. As a result , any medication that alters glomerular filtration rates or affects el ectrolyte exchange in the nephron may influence the pharmacokinetic di sposition of lithium. Concomitant use of diuretics has long been assoc iated with the development of lithium toxicity, but the risk of signif icant interactions varies with the site of pharmacological action of t he diuretic in the renal tubule. Thiazide diuretics have demonstrated the greatest potential to increase lithium concentrations, with a 25 t o 40% increase in concentrations often evident after initiation of the rapy. Osmotic diuretics and methyl xanthines appear to have the opposi te effect on lithium clearance and have been advocated historically as antidotes for lithium toxicity. Loop diuretics and potassium-sparing agents have minor variable effects. Nonsteroidal anti-inflammatory dru gs (NSAIDs) have also been associated with lithium toxicity, although the relative interactive potential of specific NSAIDs is difficult to determine. Small prospective studies have demonstrated large interindi vidual differences in lithium clearance values associated with differe nt NSAIDs. A growing body of evidence also suggests that ACE inhibitor s may impair lithium elimination, but further investigations are neede d to identify patients at risk. Anecdotal reports have linked numerous medications with the development of neurotoxicity without an apparent effect on the pharmacokinetic disposition of lithium. Antipsychotics, anticonvulsants and calcium antagonists have all been implicated in a sufficient number of case reports to warrant concern. As these medica tions have all been commonly coadministered with lithium, the relative risk of serious interactions appears to be quite low, but caution is advised.