Knr. Chengappa et al., The evolving role of topiramate among other mood stabilizers in the management of bipolar disorder, BIPOL DIS, 3(5), 2001, pp. 215-232
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.