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Editor's Note
Nov 12, 2012

Zonisamide: Comment on “Zonisamide for Weight Reduction in Obese Adults: A 1-Year Randomized Controlled Trial”

Arch Intern Med. 2012;172(20):1565. doi:10.1001/2013.jamainternmed.108

Obesity is one of the most perplexing problems we treat as internists. The condition is associated with high morbidity and mortality, and yet the cause is one of the most basic of all human pleasures: eating. No wonder we are all hoping for a magic bullet.

Zonisamide at a daily dose of 400 mg, combined with diet and lifestyle counseling, provided moderately successful weight loss in this trial (7.3 kg [3.3 kg more than placebo] at 1 year) as it did in prior trials. The problem is that the adverse effects at this dose are substantial: 18.7% of patients experienced headache, 13.3% experienced nausea/vomiting, 9.3% experienced anxiety, and 10.7% experienced impaired memory.

This trial answered a sensible question: “Could zonisamide at 200 mg achieve meaningful weight loss without substantial adverse effects?” Unfortunately, the answer is no. 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.

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.