Abstracts

RATIONALE: Zonisamide is a novel antiepileptic drug that possesses serotonergic and dopaminergic activity in addition to blockade of sodium and calcium channels. Weight loss was observed with zonisamide treatment in epilepsy clinical trials. In the current investigation, we evaluated the efficacy and safety of zonisamide in the treatment of obesity.
METHODS: 60 obese subjects were assigned to receive zonisamide or placebo (1:1 ratio) in a randomized, double-blind fashion for 16 weeks in addition to a slightly hypocaloric (500 kcal/day deficit) diet. Zonisamide dosing was flexible with a maximum of 600 mg/day. Continuation of the same treatment for an additional 16 weeks was optional for the study participants.
RESULTS: Using the available data for all randomized subjects with the last observation carried forward, the zonisamide group lost, on average, more body weight than the placebo group (5.98% [plusminus] 0.82% vs. 1.02% [plusminus] 0.40%; p[lt]0.0001) during the 16-week period. A random coefficient regression for weight change, with effects for age, race, gender, BMI, and percent body fat, estimated that zonisamide treatment over the 16-week study duration was associated with a 4.99 kg greater weight loss over placebo treatment (p[lt]0.0001). 17 of 30 subjects in the zonisamide group and 3 of 30 in the placebo group lost [gt]=5% weight (p[lt]0.0003) at Week 16.
Of the 37 subjects who entered the extension phase, 36 completed Week 32. 10 of 19 zonisamide subjects and none of the placebo subjects lost [gt]=10% weight at Week 32 (p[lt]0.0004). Zonisamide subjects had a mean weight loss of 9.37% [plusminus] 1.64% at Week 32 compared with 1.82% [plusminus] 0.73% for placebo subjects (p[lt]0.0001). The following measures of the Impact of Weight on Quality of Life (IWQOL) scale improved more significantly in the zonisamide group over the placebo group [ndash] Health (p[lt]0.0030), Work (p[lt]0.0051), Mobility (p[lt]0.0019), and Activities of Daily Living (p[lt]0.0005). Zonisamide was tolerated well with minimal side effects.
CONCLUSIONS: Zonisamide was significantly more effective than placebo as an adjunct to hypocaloric diet in the treatment of obesity. Subjects receiving zonisamide continued to lose weight in the extension phase with significant improvement of quality of life.
[Supported by: Elan Biopharmaceuticals]; (Disclosure: Grant - Elan Biopharmaceuticals)