Zonisamide for weight loss in obese adults: a randomized controlled trial.
BACKGROUND
Zonisamide is a marketed antiepileptic drug that has serotonergic and dopaminergic activity in addition to blockade of sodium and calcium channels. Weight loss was an adverse effect associated with zonisamide treatment in epilepsy clinical trials.


OBJECTIVE
To evaluate the efficacy of zonisamide for weight loss in obese adults.


METHODS
Sixteen-week randomized, double-blind, placebo-controlled trial with an optional single-blind extension of the same treatment for another 16 weeks, conducted at Duke University Medical Center from March 2001 to March 2002.


METHODS
Fifty-five (92%) women and 5 (8%) men (mean [SE] body mass index, 36.3 [0.5]; mean age, 37.0 (1.0) years).


METHODS
Patients were randomly assigned to receive zonisamide (n = 30) or placebo (n = 30). All participants were prescribed a balanced hypocaloric diet (500 kcal/d deficit) and compliance was monitored with self-rated food diaries. Zonisamide therapy was started at 100 mg/d orally, with gradual increase to 400 mg/d and further increase to 600 mg/d for patients losing less than 5% of body weight at the end of 12 weeks. Placebo dosing was identical.


METHODS
Change in body weight.


RESULTS
Of the 60 randomized patients, 51 completed the 16-week acute phase. In an intent-to-treat analysis using the available data for all randomized participants with the last observation carried forward, the zonisamide group lost more body weight than the placebo group (mean [SE], 5.9 [0.8] kg [6.0% loss] vs 0.9 [0.4] kg [1.0% loss]; t = 5.5; P<.001) during the 16-week period. A longitudinal mixed-model regression for weight change controlling for age, race, sex, body mass index, and percent body fat estimated that zonisamide treatment over the 16-week study duration was associated with significantly greater weight loss than was placebo (t = 6.4; P<.001). Seventeen (57%) of 30 in the zonisamide group and 3 (10%) of 30 in the placebo group lost at least 5% of body weight (P<.001) by week 16. Of the 37 participants who entered the extension phase, 36 completed week 32. The zonisamide group (n = 19) had a mean weight loss of 9.2 kg (1.7 kg) (9.4% loss) at week 32 compared with 1.5 kg (0.7 kg) (1.8% loss) for the placebo group (n = 17) (t = 4.0; P<.001). Zonisamide was tolerated well, with few adverse effects.


CONCLUSIONS
In this short-term, preliminary trial, zonisamide and hypocaloric diet resulted in more weight loss than placebo and hypocaloric diet in the treatment of obesity.
Gadde
Kishore M
KM
Obesity Clinical Trials Program, Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. gadde001@mc.duke.edu
Franciscy
Deborah M
DM
Wagner
H Ryan
HR
Krishnan
K Ranga R
KR
D000328:Adult; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D015992:Body Mass Index; D031204:Caloric Restriction; D003131:Combined Modality Therapy; D004038:Diet, Reducing; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008019:Life Style; D008297:Male; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy*; D010353:Patient Education as Topic; D040242:Risk Reduction Behavior; D016037:Single-Blind Method; D016896:Treatment Outcome; D015431:Weight Loss; D000078305:Zonisamide
D019440:Anti-Obesity Agents; D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide