Year: 2006
Abstract Number: 1706-P
Authors: FRANK L. GREENWAY, JAMES W. ANDERSON, RICHARD L. ATKINSON, KEN FUJIOKA, KISHORE M. GADDE, ALOK K. GUPTA, PATRICK M. O[apos]NEIL, DONALD SCHUMACHER, DIANE K. SMITH, M. J. WHITEHOUSE, SCOTT CRUICKSHANK, MARIA GUTTADAURIA, MICHAEL A. COWLEY.
Institutions: Baton Rouge, LA; Lexington, KY; Richmond, VA; San Diego, CA; Durham, NC; Charleston, SC; Charlotte, NC; Augusta, GA; San Francisco, CA; Santa Barbara, CA; New York, NY; Beaverton, OR,.
Results: In vitro electrophysiology experiments suggest naltrexone synergizes with bupropion in stimulating the proopiomelanocortin (POMC) system by blocking a beta-endorphin mediated inhibition of POMC neurons. Animal experiments confirm these findings. This proof of concept clinical trial was designed to confirm the weight loss potential of this combination in obese humans. Two hundred six healthy subjects on no regular medication except contraception or hormone replacement with a body mass index between 30 and 40 kg/m2 were randomized at 8 sites to bupropion 150 mg bid (B), naltrexone 50 mg qd (N), placebo (P) or bupropion with naltrexone (BN) for 16 weeks, and the B and BN groups were extended to week 24. At week 24 weight loss in the original groups was 3.8%, 2.2%, 0.9%, and 6.6% in the B, N, P and BN groups respectively (p<0.02, p<0.001, p<0.001 compared to BN). Nausea, the major adverse event (40%), was driven by naltrexone and led to discontinuations (12%). Other adverse events with a prevalence >10%, more frequent in the drug groups, included insomnia, dizziness and diarrhea. Bupropion and naltrexone gave synergistic weight loss. Dosage adjustment of the components may decrease nausea and increase the efficacy of the BN combination.
Category: Obesity - Clinical Treatment