Long-term pharmacologic strategies that may be used in conjunction with lifestyle changes to address the obesity epidemic have, until recently, been an unmet clinical need. Interestingly, pharmacologic interventions to date have not specifically focused on modifying the behavioral aspects of eating. Food intake is influenced by multiple pathways, including the homeostatic regulation of energy balance controlled by the hypothalamus and the mesolimbic reward system, dysregulation of which can lead to reward eating, food craving, and overconsumption of food. A growing body of evidence suggests that targeting the reward system can be a successful intervention for obesity management. Sustained-release naltrexone/bupropion is a novel combination therapy that targets both the hypothalamic melanocortin system and the reward system. In clinical trials, naltrexone/bupropion has been associated with sustained and clinically meaningful weight loss together with beneficial effects on eating behavior and improvements in cardiometabolic factors. Craving and control of food intake were also measured and correlated with improved outcome.
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