{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:11:17Z","timestamp":1791357077155,"version":"4.3.1"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2003,4,9]]},"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Zonisamide is a marketed antiepileptic drug that has serotonergic and dopaminergic activity in addition to blockade of sodium and calcium channels. Weight loss was an adverse effect associated with zonisamide treatment in epilepsy clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the efficacy of zonisamide for weight loss in obese adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Setting<\/jats:title><jats:p>Sixteen-week randomized, double-blind, placebo-controlled trial with an optional single-blind extension of the same treatment for another 16 weeks, conducted at Duke University Medical Center from March 2001 to March 2002.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>Fifty-five (92%) women and 5 (8%) men (mean [SE] body mass index, 36.3 [0.5]; mean age, 37.0 (1.0) years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Patients were randomly assigned to receive zonisamide (n = 30) or placebo (n = 30). All participants were prescribed a balanced hypocaloric diet (500 kcal\/d deficit) and compliance was monitored with self-rated food diaries. Zonisamide therapy was started at 100 mg\/d orally, with gradual increase to 400 mg\/d and further increase to 600 mg\/d for patients losing less than 5% of body weight at the end of 12 weeks. Placebo dosing was identical.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measure<\/jats:title><jats:p>Change in body weight.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 60 randomized patients, 51 completed the 16-week acute phase. In an intent-to-treat analysis using the available data for all randomized participants with the last observation carried forward, the zonisamide group lost more body weight than the placebo group (mean [SE], 5.9 [0.8] kg [6.0% loss] vs 0.9 [0.4] kg [1.0% loss]; <jats:italic>t<\/jats:italic> = 5.5; <jats:italic>P<\/jats:italic>&amp;amp;lt;.001) during the 16-week period. A longitudinal mixed-model regression for weight change controlling for age, race, sex, body mass index, and percent body fat estimated that zonisamide treatment over the 16-week study duration was associated with significantly greater weight loss than was placebo (<jats:italic>t<\/jats:italic> = 6.4; <jats:italic>P<\/jats:italic>&amp;amp;lt;.001). Seventeen (57%) of 30 in the zonisamide group and 3 (10%) of 30 in the placebo group lost at least 5% of body weight (<jats:italic>P<\/jats:italic>&amp;amp;lt;.001) by week 16. Of the 37 participants who entered the extension phase, 36 completed week 32. The zonisamide group (n = 19) had a mean weight loss of 9.2 kg (1.7 kg) (9.4% loss) at week 32 compared with 1.5 kg (0.7 kg) (1.8% loss) for the placebo group (n = 17) (<jats:italic>t<\/jats:italic> = 4.0; <jats:italic>P<\/jats:italic>&amp;amp;lt;.001). Zonisamide was tolerated well, with few adverse effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this short-term, preliminary trial, zonisamide and hypocaloric diet resulted in more weight loss than placebo and hypocaloric diet in the treatment of obesity.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.289.14.1820","type":"journal-article","created":{"date-parts":[[2003,4,10]],"date-time":"2003-04-10T01:20:03Z","timestamp":1049937603000},"page":"1820","source":"Crossref","is-referenced-by-count":242,"title":["Zonisamide for Weight Loss in Obese Adults"],"prefix":"10.1001","volume":"289","author":[{"given":"Kishore M.","family":"Gadde","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M.","family":"Franciscy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"H. Ryan","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Ranga R.","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"ref-jpc30000-1","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1001\/jama.288.14.1723","article-title":"Prevalence and trends in obesity among US adults, 1999-2000.","volume":"288","author":"Flegal","year":"2002","journal-title":"JAMA"},{"key":"ref-jpc30000-2","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1001\/jama.282.16.1519","article-title":"The spread of the obesity epidemic in the United States, 1991-1998.","volume":"282","author":"Mokdad","year":"1999","journal-title":"JAMA"},{"key":"ref-jpc30000-3","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1001\/jama.282.16.1523","article-title":"The disease burden associated with overweight and obesity.","volume":"282","author":"Must","year":"1999","journal-title":"JAMA"},{"key":"ref-jpc30000-4","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1056\/NEJM199910073411501","article-title":"Body-mass index and mortality in a prospective cohort of U.S. adults.","volume":"341","author":"Calle","year":"1999","journal-title":"N Engl J Med"},{"key":"ref-jpc30000-5","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1093\/ajcn\/69.3.347","article-title":"Benefits of weight loss in the treatment of obesity.","volume":"69","author":"Blackburn","year":"1999","journal-title":"Am J Clin Nutr"},{"key":"ref-jpc30000-6","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1001\/jama.282.16.1576","article-title":"Are health care professionals advising obese patients to lose weight?","volume":"282","author":"Galuska","year":"1999","journal-title":"JAMA"},{"key":"ref-jpc30000-8","first-page":"192","article-title":"Zonisamide: a new antiepileptic drug.","volume":"22","author":"Oommen","year":"1999","journal-title":"Clin Neuropharmacol"},{"key":"ref-jpc30000-9","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0920-1211(95)00078-X","article-title":"Effects of zonisamide on dopaminergic system.","volume":"22","author":"Okada","year":"1995","journal-title":"Epilepsy Res"},{"key":"ref-jpc30000-10","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/S0920-1211(98)00109-0","article-title":"Biphasic effects of zonisamide on serotonergic system in rat hippocampus.","volume":"34","author":"Okada","year":"1999","journal-title":"Epilepsy Res"},{"key":"ref-jpc30000-11","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/oby.1995.3.issue-1","article-title":"Assessing impact of weight on quality of life.","volume":"3","author":"Kolotkin","year":"1995","journal-title":"Obes Res"},{"key":"ref-jpc30000-12","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1002\/jbmr.5650090404","article-title":"Bone loss accompanying voluntary weight loss in obese humans.","volume":"9","author":"Jensen","year":"1994","journal-title":"J Bone Miner Res"},{"key":"ref-jpc30000-13","doi-asserted-by":"publisher","first-page":"S23","DOI":"10.1111\/epi.1999.40.issue-s5","article-title":"Zonisamide.","volume":"40","author":"Leppik","year":"1999","journal-title":"Epilepsia"},{"key":"ref-jpc30000-14","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.2165\/00003495-199856060-00019","article-title":"Sibutramine: a review of its contribution to the management of obesity.","volume":"56","author":"McNeely","year":"1998","journal-title":"Drugs"},{"key":"ref-jpc30000-15","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/0920-1211(92)90066-3","article-title":"Effects of zonisamide on extracellular levels of monoamine and its metabolites, and Ca2+ dependent dopamine release.","volume":"13","author":"Okada","year":"1992","journal-title":"Epilepsy Res"},{"key":"ref-jpc30000-16","first-page":"371","article-title":"Carbamazepine and zonisamide increase extracellular dopamine and serotonin levels in vivo, and carbamazepine does not antagonize adenosine effect in vitro: mechanisms of blockade of seizure spread.","volume":"47","author":"Kaneko","year":"1993","journal-title":"Jpn J Psychiatry Neurol"},{"key":"ref-jpc30000-17","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/BF01244998","article-title":"Simultaneous determination of in vivo hydroxylation of tyrosine and tryptophan in rat striatum by microdialysis-HPLC: relationship between dopamine and serotonin biosynthesis.","volume":"93","author":"Hashiguti","year":"1993","journal-title":"J Neural Transm Gen Sect"},{"key":"ref-jpc30000-18","doi-asserted-by":"publisher","first-page":"12564","DOI":"10.1073\/pnas.91.26.12564","article-title":"Altered striatal function in a mutant mouse lacking D1A dopamine receptors.","volume":"91","author":"Drago","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref-jpc30000-19","doi-asserted-by":"publisher","first-page":"515S","DOI":"10.1002\/oby.1995.3.issue-S4","article-title":"Dopamine receptor subtype agonists and feeding behavior.","volume":"3","author":"Terry","year":"1995","journal-title":"Obes Res"},{"key":"ref-jpc30000-20","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/S0140-6736(00)03643-6","article-title":"Brain dopamine and obesity.","volume":"357","author":"Wang","year":"2001","journal-title":"Lancet"},{"key":"ref-jpc30000-21","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1111\/aos.1984.62.issue-5","article-title":"Zinc therapy of acetazolamide-induced side effects.","volume":"62","author":"Dahl","year":"1984","journal-title":"Acta Ophthalmol"},{"key":"ref-jpc30000-22","first-page":"199","article-title":"Altered taste secondary to acetazolamide therapy.","volume":"31","author":"Miller","year":"1990","journal-title":"J Fam Pract"},{"key":"ref-jpc30000-23","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/0140-6736(90)92803-P","article-title":"Taste disturbance with acetazolamide.","volume":"336","author":"McMurdo","year":"1990","journal-title":"Lancet"},{"key":"ref-jpc30000-24","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1093\/ajcn\/69.4.584","article-title":"Model for the regulation of energy balance and adiposity by the central nervous system.","volume":"69","author":"Schwartz","year":"1999","journal-title":"Am J Clin Nutr"},{"key":"ref-jpc30000-7","volume-title":"Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report","author":"National Heart, Lung, and Blood Institute, National Institutes of Health","year":"1998"}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/articlepdf\/196347\/jpc30000_1820_1825_1708468212.83168.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:30:27Z","timestamp":1708475427000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/196347"}},"subtitle":["A Randomized Controlled Trial"],"short-title":[],"issued":{"date-parts":[[2003,4,9]]},"references-count":24,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2003,4,9]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.289.14.1820","relation":{},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2003,4,9]]}}}