A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity.
OBJECTIVE
To evaluate the efficacy and safety of topiramate (TPM) for weight loss in healthy obese subjects.


METHODS
A randomized, double-blind, placebo-controlled, dose-ranging trial was conducted. Three hundred eighty-five subjects, 18 and 75 years of age, were randomized to receive either placebo or TPM at 64, 96, 192, or 384 mg daily. Dosing began at 16 mg once daily. In week 2, the dose was increased to 16 mg twice daily. Thereafter, the dose was raised every week by 32 mg/d (16 mg twice daily) until subjects reached their target dose. Twenty-four weeks after beginning treatment, all subjects were tapered off treatment by a dose reduction of 50% per week. All participants received the same lifestyle program.


RESULTS
Mean percent weight loss from baseline to week 24 was -2.6% in placebo-treated patients vs. -5.0%, -4.8%, -6.3%, and -6.3% in the 64, 96, 192, and 384 mg/d TPM groups, respectively. Greater percentages of TPM-treated patients lost at least 5% or 10% of body weight compared with placebo. The most frequent adverse events were related to the central or peripheral nervous system, including paresthesia, somnolence, and difficulty with memory, concentration, and attention. Most events were dose-related, occurred early in treatment, and usually resolved spontaneously; only 21% receiving TPM withdrew due to adverse events compared with 11% on placebo.


CONCLUSIONS
TPM produced significantly greater weight loss than placebo at all doses.
Bray
George A
GA
Pennington Biomedical Research Center, Baton Rouge, Louisiana. Baylor Hospital, Dallas, Texas, USA. brayga@pbrc.edu
Hollander
Priscilla
P
Klein
Samuel
S
Kushner
Robert
R
Levy
Brian
B
Fitchet
Martin
M
Perry
Barbara H
BH
D000293:Adolescent; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure; D015992:Body Mass Index; D002319:Cardiovascular System / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D010919:Placebos; D012307:Risk Factors; D013997:Time Factors; D000077236:Topiramate; D015431:Weight Loss
D019440:Anti-Obesity Agents; D010919:Placebos; D000077236:Topiramate; D005632:Fructose