ABSTRACT Objective The present study examined the safety and efficacy of the fixed‐dose, extended‐release combination of naltrexone and bupropion (NB‐ER) in individuals with overweight/obesity and mild to moderate symptoms of depression. Methods Data were pooled from four double‐blind, placebo‐controlled trials. Participants with baseline Inventory of Depressive Symptomatology—Self‐Report scores ≥ 14 suggestive of mild or greater depressive symptoms were included ( N = 511). Primary outcomes were 56‐week percent weight loss and changes in depression, as well as safety data for psychiatric adverse events (PAEs), depressive symptom increases, and suicidal ideation. Multiple imputation was applied, and outcomes were compared in the intention‐to‐treat population. Results In participants with symptoms of depression, 56‐week weight loss was significantly greater with NB‐ER (5.7% ± 0.6%) than with placebo (2.7% ± 0.8%; p = 0.003). Participants experienced clinically meaningful improvements in depression of −7.1 ± 0.4 with NB‐ER and −6.7 ± 0.5 with placebo, with no significant differences between the groups. NB‐ER and placebo did not differ in safety signals including PAE occurrence (27.5% NB‐ER vs. 22.1% placebo), depressive symptom increases (9.5% NB‐ER vs. 8.8% placebo), or suicidal ideation (1.8% NB‐ER vs. 2.0% placebo). Conclusions NB‐ER appears to be both safe and effective for weight loss when offered to patients with mild to moderate symptoms of depression.
Tronieri et al. (2026) studied this question.