Zonisamide

Gadde KM, Franciscy DM, Wagner HR, Krishnan KRR. Zonisamide for weight loss in obese adults. A randomized controlled trial. JAMA 2003; 289:1820-1825.

* PRACTICE RECOMMENDATIONS

Zonisamide (Zonegran), in conjunction with a reduced-calorie diet (deficit of 500 kcal/d), resulted in an additional mean 5-kg (11-pound) weight loss compared with diet alone. This regimen was well-tolerated in obese female patients. Further evaluation of long-term side effects and continued weight loss beyond 32 weeks is needed.

* BACKGROUND

Zonisamide is an antiepileptic medication with a common side effect of causing significant weight loss. This study was conducted to assess the efficacy of using zonisamide for weight loss alone in obese adults.

* POPULATION STUDIED

Sixty adults from an outpatient clinic population and those responding to flyers were enrolled. Participants were aged 21 to 50 years, with a mean body-mass index of 36.3 and mean age of 37 years. Subjects were 92% female; 48% were African Americans and 52% Caucasians.

Exclusion criteria included endocrine-related obesity; serious/unstable medical illness; major psychiatric disorder; drug or alcohol abuse; recent weight fluctuations >4 kg; prior obesity surgery; and use of medications, herbs, or supplements that effect weight or significantly effect the cytochrome P450 system. Also excluded were women of childbearing age who were not on acceptable forms of contraception, pregnant or breastfeeding women, and those deemed unable to follow study procedures.

* STUDY DESIGN AND VALIDITY

Subjects were randomized in a double-blind fashion (allocation assignment concealed) to receive either zonisamide or identical placebo. All participants were also prescribed a hypocaloric diet (500 kcal/d deficit). Zoulsamide therapy was started at 100 mg/d orally and gradually titrated to 600 mg/d.

The study was conducted in 2 phases. Phase 1 consisted of treatment for 16 weeks with patients, study investigators, and assessors of outcomes blind to treatment group assignment (triple-blinding). A total of 51 (85%) of participants completed this phase. During phase 2, participants were allowed to continue their current medication for an additional 16 weeks, with only patients remaining blind to treatment group assignment.

A total of 36 (60%) of participants completed the full 32 week trial. Data analysis was by intention-to-treat.

Strengths of the study included triple-blind randomization with concealed allocation. Weaknesses included a small sample size and short follow-up, making it difficult to assess long-term safety and outcomes. Only 5 men were enrolled in this trial and all received zonisamide. Thus, we cannot reliably extrapolate study conclusions to men.

* OUTCOMES MEASURED

The primary outcome measured was change in absolute body weight. Secondary outcomes included percent weight change and the number of participants in each group to reach a weight loss of at least 5% and 10% of baseline body weight. Other measures included adverse treatment effects and an Impact of Weight on Quality of Life (IWQOL) questionnaire.

* RESULTS

In the initial phase of the trial, the zonisamide group lost significantly more weight than the placebo group (mean 5.9 kg vs 0.9 kg; P<.001). A total of 57% of patients in the zonisamide group vs 10% in the placebo group lost at least 5% of their initial body weight, and 23% of those in the zonisamide group vs 0% in the placebo group lost at least 10% of initial body weight (P=.05). After the extension phase, the zonisamide group had a mean weight loss of 9.2 kg vs 1.5 kg for the placebo group.

As measured by the IWQOL questionnaire, health, work, mobility, and activities of daily living were all significantly improved in the zonisamide group at both 16 and 32 weeks. Ten patients in the zonisamide reported fatigue vs 1 patient in the placebo group. Otherwise, no adverse effects were reported differentially between the groups.

Caroline S. Kim, MD, Department of Family Medicine, University of Virginia Health Sciences Center, Charlottesville. E-mail: csk3g@virginia.edu.

COPYRIGHT 2003 Dowden Health Media, Inc.
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