Semaglutide, a popular weight-loss medication, does not increase the risk of depression or suicidal thoughts, according to a recent analysis.

The post hoc analysis of the STEP 1, 2, 3, and 5 trials evaluated the psychiatric safety of semaglutide 2.4 mg, a GLP-1 receptor agonist indicated for weight management, in adults with overweight or obesity and no history of major psychopathology. Across 3,681 participants—3,377 from the STEP 1, 2, and 3 trials and 304 from STEP 5—no clinically significant differences in depressive symptoms or suicidal ideation were observed between the semaglutide and placebo groups, as measured by the Patient Health Questionnaire-9 (PHQ-9) and the Columbia-Suicide Severity Rating Scale.

Baseline PHQ-9 scores indicated minimal depressive symptoms in both groups (semaglutide: 2.0, placebo: 1.8). By week 68, mean scores remained low, with semaglutide patients showing no significant increase in depressive symptoms (2.0) compared to placebo (2.4), resulting in an estimated treatment difference of -0.56 (95% confidence interval [CI], -0.81 to -0.32; P < .001). Participants in the semaglutide group had a statistically lower likelihood of transitioning to a more severe depression category than those receiving placebo (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001). However, the reduction in depressive symptoms, while statistically significant, was not considered clinically meaningful by the authors.

The incidence of suicidal ideation was low, with 1% or fewer participants affected in both groups, and no statistically significant differences in suicidal behavior. Psychiatric adverse events, including sleep disturbances and anxiety, were similarly distributed across treatment arms, though headache and dizziness occurred more frequently in the semaglutide group.

This analysis, published in JAMA Internal Medicine, suggests that semaglutide 2.4 mg does not increase the risk of depressive symptoms or suicidal ideation/behavior in participants with obesity or overweight without significant psychiatric histories. The study highlights the importance of mental health monitoring for patients with obesity who are undergoing weight management treatment, due to potential psychiatric comorbidities associated with obesity.

Full disclosures can be found in the published study.