People without known major psychiatric illness who are treated with semaglutide for obesity do not appear to be at increased risk for depression or suicidal thinking or behavior compared to patients receiving a placebo, according to a report yesterday in JAMA Internal Medicine.
Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that has been shown to produce clinically significant weight loss in patients with obesity or Type 2 diabetes. However, both the Food and Drug Administration and the European Medicines Agency have been monitoring the safety of GLP-1 receptor agonists following postmarketing surveillance reports of depression and suicidal ideation in people prescribed these medications, noted Thomas Wadden, Ph.D., of the University of Pennsylvania Perelman School of Medicine, and colleagues.
Wadden and colleagues analyzed pooled data from four phases of the Semaglutide Treatment Effect in People with Obesity (STEP) trial that tested 2.4 mg of semaglutide in patients with obesity. (One phase of the trial also included patients with Type 2 diabetes.). The STEP trial excluded participants who had a history of severe psychiatric illness—such as major depression or schizophrenia—or suicide attempt, as well as individuals who screened for elevated depressive symptoms or suicidal ideation within the past 30 days. The original STEP trial and this secondary analysis were funded by Novo Nordisk A/S, and researchers from the company were involved in this analysis.
The analysis included 3,681 patients (73% female). Across the four trials, only 2.8% of patients treated with semaglutide had a postbaseline Patient Health Questionnaire score of 15 or greater—suggestive of moderately severe or greater symptoms of depression requiring evaluation by a mental health professional—compared with 4.1% of those receiving placebo. Suicidal ideation as assessed by the Columbia–Suicide Severity Rating Scale was less than 1% in all trials, with no differences between treatment groups.
Wadden and colleagues noted that a small number of patients taking semaglutide may experience depression or suicidal thoughts “which may be related to psychosocial complications of obesity or other factors, including life stressors.”
They concluded: “We encourage clinicians to monitor mental health in people with overweight or obesity, including those prescribed semaglutide, 2.4mg, or similar medications. This is essential for ensuring that these individuals obtain the psychiatric care they require to manage anxiety, depression, and related psychiatric complications, which may occur in the presence or absence of weight management interventions.”
In another study published in JAMA Internal Medicine yesterday, Peter Ueda, M.D., Ph.D. at Sweden’s Karolinska Institutet and colleagues analyzed nearly a decade of patient data from Swedish and Danish health registries and found no evidence that GLP-1 RAs increased the risk of suicide death in adults relative to those who took another class of diabetes medications (sodium-glucose cotransporter-2 inhibitors).
For more information, see the Psychiatric News article “Blockbuster Weight Loss Drugs Not Tied to Suicidality, Studies Show.”
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