Obesogenic Medications and Weight Gain Over 24 Weeks in Patients with Depression: Results from the GUIDED Study

Weight gain is a common side-effect of medications used to treat major depressive disorder (MDD). We sought to estimate the frequency of weight gain for obesogenic medications prescribed for MDD and to evaluate if bupropion mitigated risk for weight gain. We analyzed a prospective cohort of patients with weight available at baseline and 12 weeks (n = 1,032) or 24 weeks (n = 871) in a post hoc analysis of the <b>G</b>enomics <b>U</b>sed to <b>I</b>mprove <b>DE</b>pression <b>D</b>ecisions (GUIDED) study of patients with MDD who failed at least one medication trial. We compared weight gain between those on versus not on medications with high risk for weight gain, including a subgroup receiving combination treatment with bupropion. A second analysis evaluated weight gain across traditional medication classes, adjusting for potential confounding variables. Those on medications identified as high risk for weight gain were significantly more likely to experience clinically significant weight gain (≥3%) at 12 weeks (29.3% vs. 16.3%, <i>p</i> < .001) and 24 weeks (33.5% vs. 23.5%, <i>p</i> = .015). No protection from clinically significant weight gain was observed among patients treated with a high-risk medication concomitantly with bupropion (N = 31, 35% and 52% with clinically significant weight gain at 12 and 24 weeks). Antipsychotic medications and tricyclic antidepressants were most often associated with clinically significant weight gain. This study helps quantify the real-world risk of weight gain for patients with MDD on medications with high risk for weight gain, especially for patients taking antipsychotics. Concurrent treatment with bupropion does not appear to mitigate the weight gain risk.