Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials


  • These trials were sponsored by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. SFK, AK and RL are employees of Johnson & Johnson Pharmaceutical Research & Development. WHO is an employee of Ortho-McNeil Janssen Scientific Affairs, L.L.C.

Stuart F. Kushner, MD, Director, CNS Medical Leader, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA. Fax: +1-609-730-2069; e-mail:


Objective:  To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder.

Methods:  In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of ≥1 previous manic or mixed episodes, and ≥20 Young Mania Rating Scale (YMRS) score were randomized to double-blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9-week double-blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study.

Results:  Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, −5.1 to −8.4). Mean YMRS reductions in lithium-treated groups were significantly greater (p ≤ 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo.

Conclusions:  These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression. Lithium was confirmed as an effective therapy in this population.