Context 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.
Design and Setting 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.
Participants Fifty-five (92%) women and 5 (8%) men (mean [SE] body mass index, 36.3
[0.5]; mean age, 37.0 (1.0) years).
Interventions 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.
Main Outcome Measure 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.
Conclusion In this short-term, preliminary trial, zonisamide and hypocaloric diet
resulted in more weight loss than placebo and hypocaloric diet in the treatment