The evolving role of topiramate among other mood stabilizers in the management of bipolar disorder

Objectives: Topiramate, a structurally novel anticonvulsant, is being S eva luated for other neurological conditions such as migraine, neuropathic pain , and essential tremor, and also for psychiatric conditions such as bipolar disorder, bulimia, post-traumatic stress disorder, and schizoaffective dis order, in addition to obesity. This article will focus on the use of topira mate for bipolar disorder. Methods: The pharmacological profile of topiramate is compared to other est ablished and putative mood stabilizers, and a rationale for its use in bipo lar disorder is presented. Data from open clinical trials of topiramate for depression, mania, and rapid-cycling bipolar disorder are summarized. Prel iminary data from one pilot dose-finding, double-blind, random-assignment, placebo-controlled, 3-week parallel group study of two doses of topiramate for acute bipolar I mania is reported. Safety data regarding topiramate was reviewed. Finally, the potential place of this agent in bipolar illness is considered. Results: The pharmacological advantages for topiramate are low protein bind ing, minimal hepatic metabolism and mainly unchanged renal excretion, a 24- h half-life, and minimal drug interactions. Open clinical studies suggest a 50-65% response for refractory bipolar mania, and a 40-56% response for re fractory bipolar depression in mainly add-on treatment. Open clinical studi es of topiramate for rapid-cycling subjects and those for comorbid bulimia, substance abuse, post-traumatic stress, migraine, and obesity report effec tiveness. The primary efficacy endpoint data (change from baseline Y-MRS to tal scores) of the placebo-controlled, random assignment parallel group pha se II dose-finding study were not statistically significant. However, once the antidepressant-associated manias (28 of the sample, of 97 subjects) wer e excluded from the controlled study, the post-hoe analyses indicated the h igher dose (512 mg/day) topiramate treatment group showed a statistically s ignificant reduction in endpoint Y-MRS change scores as compared to placebo (p < 0.03). Adverse effects of topiramate in bipolar subjects include atte ntion, concentration and memory problems, fatigue, sedation, transient para esthesias, nausea, and anorexia. Some subjects experience word-finding diff iculty. Weight loss may be seen in several topiramate-treated subjects with bipolar disorder. Conclusions: Topiramate appears to show promise as an addition to the agent s available to treat bipolar disorder. More definitive controlled data on t he efficacy of topiramate in the acute and continuation phases as well as f or the prophylaxis either as monotherapy or as combination treatment of bip olar disorder are ongoing, and the results are awaited.