Published September 10, 2024 News and Trends Ozempic, Other GLP-1s Not Associated With New Depression, Suicidality Philadelphia—Approximately one in eight U.S. adults have used a GLP-1 drug such as Ozempic or Mounjaro at some point in their life, according to a recent KFF survey, which added that one-half of them—about 6% of adults or more than 15 million people—currently have a prescription.So, it is no surprise that concerns about possible links between use of the drug and the development of depression or suicidal ideation/behavior in overweight or obese people with no known major psychopathology were taken very seriously. Now, a post hoc analysis of the STEP 1, 2, and 3 trials and STEP 5 trial over 68 and 104 weeks, respectively, has identified no clinically meaningful differences in mean Patient Health Questionnaire 9 scores throughout the trials between the semaglutide, 2.4 mg, and placebo groups. The Perelman School of Medicine, University of Pennsylvania–led study found that the proportion of participants reporting suicidal ideation/behavior (as assessed by the Columbia-Suicide Severity Rating Scale) were also similar between the groups.“The results of this post hoc analysis suggest that the risk of developing symptoms of depression or suicidal ideation/behavior was similar between semaglutide, 2.4 mg, and placebo,” the authors wrote in the Journal of the American Medical Association Internal Medicine.The study pointed out that obesity is associated with a range of psychosocial complications, “making psychiatric safety a consideration for treating people with obesity.” Yet, little research has been done on the psychiatric safety of newly available antiobesity medications.That is why the study team—which had industry support—sought to evaluate the psychiatric safety of SC semaglutide, 2.4 mg, once weekly in people without known major psychopathology.The post hoc analysis of pooled data from the randomized, double-blind, placebo-controlled, multicenter phase IIIa STEP 1, 2, and 3 trials (68 weeks; 2018–2020) and phase IIIb STEP 5 trial (104 weeks; 2018–2021) included adults with overweight or obesity. Participants in STEP 2 participants also had type 2 diabetes (T2D). The intervention was semaglutide, 2.4 mg, vs placebo.The researchers assessed depressive symptoms and suicidal ideation/behavior using the Patient Health Questionnaire (PHQ-9) and Columbia–Suicide Severity Rating Scale, respectively. They also investigated psychiatric and nervous system disorder adverse events in the more than 3,500 participants. Most of those in the study were women with a mean age in their late 40s.“In the STEP 1, 2, and 3 trials, mean (SD) baseline PHQ-9 scores for the semaglutide, 2.4 mg, and placebo groups were 2.0 (2.3) and 1.8 (2.3), respectively, indicating no/minimal symptoms of depression,” the authors explained. “PHQ-9 scores at week 68 were 2.0 (2.9) and 2.4 (3.3), respectively; the estimated treatment difference (95% CI) between groups was –0.56 (–0.81 to –0.32) (P <.001).”The researchers also advised, “Participants treated with semaglutide vs placebo were less likely to shift (from baseline to week 68) to a more severe category of PHQ-9 depression (odds ratio, 0.63; 95% CI, 0.50-0.79; P <.001). Based on the Columbia–Suicide Severity Rating Scale, 1% or fewer of participants reported suicidal ideation/behavior during treatment, with no differences between semaglutide, 2.4 mg, and placebo. Psychiatric disorder adverse events were generally balanced between groups. Similar results were observed in STEP 5.”The results of the post hoc analysis suggest that treatment with semaglutide, 2.4 mg, did not increase the risk of developing symptoms of depression or suicidal ideation/behavior versus placebo and was associated with a small—but statistically significant reduction—in depressive symptoms that was not considered clinically meaningful, according to the researchers. “People with obesity should be monitored for mental health concerns so they can receive appropriate support and care,” the authors added.Background information in the study noted that semaglutide is a GLP-1 receptor agonist (GLP-1RA) that is approved globally for weight management at a once-weekly dosage of 2.4 mg. Based on past research, after 68 weeks, “semaglutide, 2.4 mg, produces an approximately 10% to 15% mean reduction in baseline body weight, which is associated with clinically meaningful improvements in numerous health outcomes, including cardiovascular events in people with overweight or obesity and a history of a cardiovascular event (but not T2D),” the study pointed out.While neither semaglutide, 2.4 mg, nor liraglutide, 3.0 mg, another GLP-1RA approved for weight management, was associated with increased psychiatric AEs versus placebo in phase III trials, the European Medicines Agency and the FDA are actively monitoring the psychiatric safety of GLP-1RAs following postmarketing surveillance reports of depression, suicidal ideation, and suicidal behavior in people prescribed the medications for T2D or weight management. So far, however, neither agency has found evidence of a causal association, according to the report.The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.