Semaglutide similarly effective for patients on antidepressants

Semaglutide is a drug that mimics a hormone called glucagon-like peptide-1 (GLP-1) to target areas of the brain that regulate appetite and food intake. The drug is available in two forms: Ozempic, a diabetes treatment, and Wegovy, a higher dose of the drug approved for weight loss.

Wegovy was initially tested in four STEP clinical trials, which included over 3,500 overweight or obese adult patients. Although the trials excluded patients with major depression, patients who were taking antidepressants for other conditions, such as anxiety, neuropathy, panic disorder, and more, were included. In total, 539 patients reported taking antidepressants at baseline.

According to a new post-hoc analysis of the trial data, patients taking antidepressants lost a similar amount of weight while on Wegovy compared to those who were not taking antidepressants. Patients on antidepressants lost an average of 10.7% to 19% of their baseline body weight while patients not on antidepressants lost 9.5% to 15.9%.

"In all trials in the semaglutide treatment arm, the change from baseline in percent body weight loss was greater in participants on antidepressants versus those who were not," said Robert Kushner, an advisor for Novo Nordisk from the Northwestern University Feinberg School of Medicine. "In the placebo arm of the trials, the opposite was observed."

However, total adverse events, as well as gastrointestinal and psychiatric adverse events, were more prevalent among patients taking antidepressants than those who were not. Across the four clinical trials, between 97.6% to 100% of patients taking antidepressants reported adverse events compared to 86.7% to 95.3% of those who were not. A similar trend was observed among patients in the placebo groups.

There were no significant differences in reports of suicidal ideation among patients who were taking antidepressants and those who were not. Only a few patients, whether taking antidepressants or not, reported suicidal ideation in the trials.

More research is needed on weight-loss drugs and mental health issues

Although several antidepressants can lead to weight gain, people with major depression are often excluded from weight-loss research. This has led to an evidence gap on how weight-loss drugs affect patients on antidepressants.

"Emotional and psychological behaviors affecting control over eating and satiety are associated with obesity and depression and can contribute to metabolic dysfunction and weight gain in a mutually reinforcing cycle," Kushner said.

As more people take Wegovy and other similar weight-loss drugs, there have been a growing number of reports of potential side effects, including severe mental health issues. According to FDA's adverse event reporting system, there have been 489 reports of patients experiencing anxiety, depression, or suicidal thoughts while on semaglutide.

These reports have led regulators in Europe, including the European Medicines Agency and the U.K's Medicines and Healthcare products Regulatory Agency, to investigate the potential link between semaglutide and other GLP-1 drugs and mental health issues. FDA has also said that it is monitoring the situation.

Currently, it's not clear whether these reported mental health issues are caused by weight-loss medications, but health experts say that more research is needed to understand how the drugs affect patients with a history of depression or suicidal ideation.

"If you give the same drug to a different population, you could, theoretically at least, have different outcomes," said Susanne Miedlich, an associate professor of medicine at the University of Rochester Medical Center. (Haelle, MedPage Today, 10/16)

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