Naltrexone HCI/bupropion HCI for chronic weight management in obese adults: patient selection and perspectives

Naltrexone, an opiate antagonist, and bupropion, a noradrenergic/dopaminergic antidepressant, have many effects on the reward systems of the brain. These medications impact eating behavior, presumably via their impact on food reward. However, only bupropion induces weight loss in obese individuals, while naltrexone does not have any appreciable effect. The combination of 32 mg of naltrexone and 360 mg of bupropion in a sustained-release combination pill form has been recently approved for obesity treatment. Studies have shown that the combination of these two medications is more effective in inducing weight loss, when combined with lifestyle intervention and calorie reduction, than each individual medicine alone. The naltrexone-bupropion combination, when combined with lifestyle intervention and modest calorie reduction, seems to be quite effective for 6-month and 1-year outcomes for clinically significant weight loss (over 5% of total body weight). These medications are not devoid of serious side effects, however, and careful patient selection can reduce dramatic complications and increase positive outcomes. This paper reviews existing weight loss clinical trials with bupropion and the bupropion-naltrexone combination. Additionally, the rationale for the suggested patient selection and clinical strategies for special patient populations are discussed.