Lamotrigine update and its use in mood disorders

OBJECTIVE: To provide a qualitative, systematic update and review of the pharmacology, pharmacokinetics, efficacy in mood disorders, adverse effects, and costs of lamotrigine. DATA SOURCES: Citations obtained from MEDLINE searches (1985-September 2001) using lamotrigine as a text word, articles identified in reference lists of pertinent articles, abstracts presented at conferences, and research data from GlaxoSmithKline. DATA EXTRACTION: English-language articles were considered for possible inclusion. Each title and abstract was examined to determine whether the publication contained up-to-date information relevant to the objective. Twenty clinical trials that provided data on response rates in mood disorders were tabulated. DATA SYNTHESIS: Lamotrigine's primary action is to modulate voltage-gated sodium channels. Evidence suggests that it decreases glutamate transmission, directly reduces calcium influx, mildly blocks transmitter reuptake, and alters intracellular mechanisms of resting transmitter release. The average half-life of lamotrigine is approximately 24 hours, but decreases to approximately 7.4 hours when used concurrently with phenytoin, and increases to approximately 59 hours with valproic acid. Seven of the 20 clinical trials were randomized, double-blind, and controlled. Existing data are inadequate to evaluate lamotrigine use in major depression. The pooled response rates for patients with depressed, manic, mixed, and rapid cycling bipolar disorder were similar, ranging from 52% to 63%. Adverse effects are infrequent when the drug is used alone, but become more frequent when lamotrigine is combined with other anticonvulsants. While most rashes are mild, approximately 1 in 500 patients develops exfoliative dermatitis. A slow upward dose titration is recommended to reduce the incidence of serious rash, but this may delay the attainment of adequate dosage for 6 weeks. Lamotrigine has positive effects on cognitive function, but occasionally produces insomnia. Lamotrigine costs 2-4 times more than lithium, carbamazepine, and generic valproic acid. CONCLUSIONS: When efficacy, adverse effects, and cost are considered, lamotrigine should probably be reserved as a second-line agent for bipolar depression.

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