Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials.
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 > or =1 previous manic or mixed episodes, and > or =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 < or = 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.
Kushner
Stuart F
SF
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ 08560, USA. skushner@prdus.jnj.com
Khan
Akbar
A
Lane
Rosanne
R
Olson
William H
WH
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D018692:Antimanic Agents / Q000008:administration & dosage; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008094:Lithium / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D000077236:Topiramate; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
D000927:Anticonvulsants; D018692:Antimanic Agents; D000077236:Topiramate; D005632:Fructose; D008094:Lithium