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Zonisamide enhanced weight loss in obese adults
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Lifestyle interventions have been established as the first line of treatment against obesity, but researchers have looked to pharmacologic options. Preliminary data from a trial funded by the National Institute of Diabetes and Digestive and Kidney Diseases suggest that zonisamide enhanced weight loss in conjunction with diet and lifestyle counseling. However, researchers are assessing the high incidence of adverse events associated with this use.
In a randomized, double blind, parallel-group, three-arm trial, researchers found that zonisamide, an antiepileptic medication classified as a sulfonamide and unrelated to other antiseizure agents, effectively enhanced weight loss at a 400-mg dose after 1 year.
From January 2006 to September 2011, 225 obese patients, including 134 women and 91 men without diabetes, were randomly assigned to placebo (n=74), zonisamide 200 mg (n=76) or zonisamide 400 mg (n=75), in addition to diet and lifestyle counseling.
Kishore M. Gadde, MD, assistant professor of psychiatry and behavioral sciences at Duke University School of Medicine, and colleagues found that zonisamide 400 mg daily led to a 3.3 kg greater weight loss compared with diet and lifestyle interventions alone. Additionally, zonisamide 200 mg proved non-efficacious, they wrote.
Of the 225 obese patients, 218 participated in follow-up assessments of changes in body weight (–4 kg; 95% CI, –5.8 to –2.3 kg) for placebo, (–4.4 kg; 95% CI, –6.1 to –2.6 kg) for zonisamide 200 mg, and (–7.3 kg; 95% CI, –9 to –5.6 kg) for zonisamide 400 mg, according to data.
Gadde and colleagues found that 23 patients (31.1%) assigned to placebo obtained a 5% or greater weight loss compared with 26 (34.2%) assigned to zonisamide 200 mg, and 41 (54.7%) assigned to zonisamide 400 mg.
The researchers wrote that altered taste, constipation, diarrhea, dry mouth, headache, fatigue, nausea/vomiting, somnolence, language/speech problems, impaired attention/concentration, memory problems and anxiety-related and depression-related adverse events were more common in patients taking either zonisamide 200 mg or 400 mg, or both.
In an accompanying editorial, Mitchell H. Katz, MD, director of the Los Angeles County Department of Health Services, wrote that zonisamide 200 mg cannot achieve meaningful weight loss without substantial adverse effects.
“Weight loss with the lower dose of zonisamide was almost identical to weight loss with placebo. Low-dose zonisamide produced adverse effects without a primary effect,” Katz wrote. “We need to continue to search for better weight loss aids. Until then, we have an effective and safe (albeit difficult to adhere to) regimen: eating less and exercising more.”
The high risk for adverse events has led the researchers to suggest further studies examining zonisamide as an option for weight-loss management in obese adults.
Disclosure: See the study for a full list of disclosures.
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