Weight Reduction in Obese Patients with Zonisamide
Obese patients who have not achieved adequate weight loss through changes in lifestyle have few nonsurgical therapeutic options. In a recent 16-week trial, the antiepileptic drug zonisamide demonstrated weight loss efficacy in obese adults (-5.9 vs -0.9 kg with placebo), with additional weight loss achieved in the 16-week extension phase of the trial.
In the above-mentioned trial, the daily zonisamide dose was titrated to 400 mg for all patients by week 7 and to 600 mg for patients who did not lose at least 5% of their weight. A review of trial data found that patients who did not have adequate weight loss at 400 mg had no appreciable weight loss at 600 mg.
Researchers have noted that because the dose was increased to 400 mg regardless of the degree of weight loss, it remained unknown whether a lower dose would have been as effective in a longer duration. In addition, because treatment with placebo led to only a 0.9 kg weight loss, the researchers felt the lifestyle intervention in the trial was not effective.
The researchers recently conducted a study to determine if the addition of 400 mg of zonisamide daily augments weight loss that can be achieved with a fair quality lifestyle intervention administered in a primary care setting and if a lower dose of zonisamide (200 mg) is also efficacious. They reported results of the study in Archives of Internal Medicine [2012;172(20):1557-1564].
The 1-year, randomized, double-blind, placebo-controlled trial was conducted from January 9, 2006, through September 20, 2011, at the Duke University Medical Center. The study cohort included 225 obese participants (mean body mass index of 37.6), of whom 59.6% (n=143) were women. Mean age was 43 years, 21.0% had a history of depression, and 8.9% were taking antidepressants.
The participants were randomly assigned to 1 of 3 treatment groups: (1) placebo (n=74);
(2) 200 mg of zonisamide (n=76); or (3) 400 mg of zonisamide (n=75). The study intervention also included diet and lifestyle counseling by a dietitian for 1 year. The primary outcome measure was change in body weight at 1 year.
Secondary outcomes included proportions of patients achieving 5% and 10% weight loss and changes in waist circumference, blood pressure, lipid levels, and other relevant blood test results. Safety outcomes included frequency of adverse events and a change in the Hospital Anxiety and Depression Scale depression score.
Of the 225 patients assigned to a group, 96.9% (n=218) provided 1-year follow-up assessments. The primary end-point assessment was available for 71 in the placebo group, 73 in the 200-mg group, and 74 in the 400-mg group.
Compared with patients taking placebo, those in the 400-mg group had more weight loss (4 kg in the placebo group versus 7.3 kg in the 400-mg group; P=.009). The 200-mg dose was not superior to placebo (4 kg vs 4.4 kg; P=.79).
In further analyses, 31.1% (n=23) patients in the placebo group achieved a ≥5% weight loss compared with 34.2% (n=26) in the 200-mg group (P=.72 vs placebo) and 54.7% (n=41) in the 400-mg group (P=.007 vs placebo). Further, 8.1% (n=6) of the placebo group had a weight loss of ≥1%, compared with 22.4% (n=22) in the 200-mg group (P=.02) and 32.0% (n=24) in the 400-mg group (P<.001).
Waist circumference decreased in all groups; compared with placebo, there was a greater decrease in the 400-mg group. Other secondary outcomes were favorable with all treatments with no significant between-group differences. Compared with placebo, gastrointestinal, nervous system, and psychiatric adverse events occurred at a higher incidence with zonisamide.
In conclusion, the researchers said, “Zonisamide at the daily dose of 400 mg moderately enhanced weight loss with diet and lifestyle counseling, but had a high incidence of adverse events.”