Semaglutide for Weight Loss: No Depression or Suicide Risk

Semaglutide, a weight loss medication, did not increase the risk of depressive symptoms, suicidal thoughts, or suicidal behavior. The new study was led by researchers from the University of Pennsylvania's Perelman School of Medicine and published this week in JAMA Internal Medicine (1^✔ ✔Trusted Source
Penn study finds taking semaglutide for weight management does not increase risk of depression or suicidal behavior in people without known major psychopathology

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The European Medicines Agency (EMA) and the Food and Drug Administration (FDA) are continuously checking on the psychiatric safety of semaglutide and related drugs after post-marketing surveillance reports of suicidal behavior, depression, and thoughts in patients taking the drugs to treat obesity or type 2 diabetes.

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Role of Semaglutide in Obesity Treatment

Semaglutide has emerged as a significant advancement in the field of weight management. The medication, which was first created as a type 2 diabetes treatment, received a lot of attention after clinical trials showed that it decreased baseline body weight by 10% to 15%.

These medications are weekly injections that are becoming more common for medical professionals to recommend to their patients. In 2023, semaglutide was prescribed to nearly 5 million Americans, of whom roughly 4 out of 10 took it for weight management.

The new study, led by Thomas Wadden, PhD, a professor of Psychology in Psychiatry and the former director of Penn’s Center for Weight and Eating Disorders, analyzed data from over 3,500 participants across four major clinical trials. Researchers examined data from the Semaglutide Treatment Effect in People with Obesity (STEP) trials – STEP 1, 2, 3, and 5. These studies were crucial in gaining approval from the FDA to use semaglutide 2.4 mg for obesity.

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Mental Health Considerations in Semaglutide Use

The STEP trials provide strong evidence that semaglutide 2.4 mg reduces body weight and improves numerous health complications associated with obesity. However, further study is needed on the psychiatric safety of semaglutide 2.4 mg when used by persons with current major depressive disorder, other serious mental illness (such as schizophrenia), or a history of suicide attempts. Individuals with such conditions were not included in the STEP trials.

The study examined changes in depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9) and assessed suicidal ideation and behavior using the Columbia Suicide Severity Rating Scale.

Across the 68-week STEP 1-3 trials, semaglutide-treated participants, as compared to those who received a placebo, did not show an increased risk of developing moderately severe symptoms of depression or suicidal thoughts or behavior. Similar findings were observed in the 104-week STEP 5 study.

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Depression and Suicidal Thoughts with Semaglutide

Examining all four STEP trials, researchers found that 1% or fewer of participants reported suicidal ideation or behavior during treatment, with no differences between semaglutide 2.4 mg and placebo. Moreover, only 2.8% of the semaglutide-treated participants, versus 4.1% of those who received placebo, reported levels of depression at some point during treatment that required evaluation by a mental health professional.

These rates are consistent with the risk of significant depression in the general population. “It is certainly possible that individuals with overweight or obesity who take semaglutide may experience depressive symptoms or suicidal ideation or behavior, but the data suggest that persons not taking semaglutide – in the placebo group in this study - are equally likely to experience these conditions,” said Gregory Brown, PhD, a study co-author and Director of the Penn Center for the Prevention of Suicide at the Perelman School of Medicine.

Wadden and Brown noted that their study’s findings for semaglutide are consistent with results of the FDA’s most recent analysis of post-marketing surveillance data for this class of medications which did not find “evidence that use of these medicines causes suicidal thoughts or actions."

Reference:

1. Penn study finds taking semaglutide for weight management does not increase risk of depression or suicidal behavior in people without known major psychopathology - (https:www.pennmedicine.org/news/news-releases/2024/september/semaglutide-and-mental-health#:~:text=PHILADELPHIA%E2%80%94%20Taking%20the%20weight%20loss,at%20the%20University%20of%20Pennsylvania)

Source-Eurekalert