ABSTRACT
This chapter compares the benefits and harms of naltrexone-bupropion using evidence from clinical study reports (CSRs). Searches were conducted on FDA and EMA websites, PubMed, and Clinicaltrials.gov to identify pivotal trials; a freedom of information request was then sent to the EMA. Pivotal, phase III placebo-controlled trials were included. The risk of bias was assessed using the Cochrane criteria, and the quality of the evidence was assessed using GRADE. The random-effects model was used for meta-analyses. Over a 27-month period, 31 batches of CSR documents were received; these contained over 65,000 pages of data from four pivotal trials (n=4536). Significantly more participants who took naltrexone-bupropion achieved ≥5% weight loss compared with placebo: RR=2.1 (2.09 to 1.35, P=0.001, GRADE=low, NNTB=5 (3 to 17). The effect of naltrexone-bupropion on other cardiovascular profiles was uncertain because of incomplete outcome data. Naltrexone-bupropion significantly increased the risk of adverse events: RR=1.11 (1.05 to 1.18, P=0.0004, GRADE=low, NNTH=12 (7 to 27); serious adverse events: RR=1.70 (1.38 to 2.1), P<0.00001, GRADE=moderate, NNTH=21 (13 to 38); and discontinuation because of adverse events: RR=1.92 (1.65 to 2.24), P<0.00001, GRADE=moderate, NNTD=9 (8 to 13). In conclusion, naltrexone-bupropion significantly reduces body weight but significantly increases the risk of adverse events. Post-marketing trials are warranted.
