May 14, 2025

expert reaction to systematic review and meta- analysis on GLP-1 receptor agonists and mental health

A systematic review published in JAMA Psychiatry looks at weight loss drugs (GLP-1 receptor agonists) and mental health.

Prof Stella Chan, Charlie Waller Chair in Evidence-based Psychological Treatment, University of Reading, said:

“This is a robustly conducted systematic review and meta-analysis, reporting the encouraging findings that these drugs improve quality of life in patients with obesity and diabetes. While it is positive to note that the drugs do not appear to increase the risk for psychiatric illnesses, as the authors noted, the findings were primarily based on clinical trials that excluded patients with psychiatric symptoms and that the range of mental health outcomes was limited. As such, the findings should be taken to indicate preliminary evidence that these drugs are safe, but that more research is needed to draw definitive conclusions.”

Dr Paul Keedwell, Consultant Psychiatrist and Fellow of the Royal College of Psychiatrists, said:

“This study helps to settle an ongoing debate about how popular weight-loss drugs like Wegovy and Mounjaro might affect mental health. By analysing data from over 100,000 people in well-run clinical trials, the researchers found no signs that these drugs increase the risk of depression, anxiety, or suicidal thoughts. 

“Rather, some people reported feeling slightly better emotionally while taking them—likely because of the benefits of weight loss and improved physical health. This is consistent with a previous review which indicated a mood boosting effect of these drugs.

“However, there is an important caveat. By design, people with a history of mental health problems were invariably excluded from the studies that were analysed. So the findings may not apply to everyone.

“There have been some case reports where people with previous depression or anxiety said the drugs made their symptoms worse, possibly by affecting parts of the brain linked to pleasure and motivation.

“A large study based on 160,000 real-world medical records showed that people taking GLP-1 drugs were nearly twice as likely to experience depression, anxiety, or suicidal thoughts compared to those not taking them. The difference was that people with a history of mental health problems were not excluded.

“So for most people, these drugs seem mentally safe—and may even help mood—but for those with a history of mental illness, there may be a risk. More research is needed, and anyone with past mental health issues should speak with a doctor before starting them.”

‘Glucagon-Like Peptide 1 Receptor Agonists and Mental Health’ by Aueliane C. S. Pierret et al. was published in JAMA Psychiatry at 16:00 UK time on Wednesday 14 May. 

DOI: 10.1001/jamapsychiatry.2025.0679

Declared interests

Prof Stella Chan: No conflict of Interest.

Dr Paul Keedwell: No conflicts of interest.