A recent study published in Current Neuropharmacology suggests that GLP-1 receptor agonists, drugs commonly used for weight loss and conditions like diabetes, may increase the risk of depression and suicidal thoughts in some users. The research, led by an international team of scientists, calls for a more personalized approach to prescribing these drugs, with a focus on genetic testing to better identify at-risk individuals.
The study, which involved 24 researchers from the United States, Brazil, Iran, and Israel, examined genetic pathways that could explain why certain individuals might experience depressive symptoms when using GLP-1 agonists like Ozempic. By applying advanced pharmacogenomic methods, the team identified several key genes involved in mood regulation, including DRD3, BDNF, and CREB1. Disruption in these genes, which play a significant role in dopamine signaling, could contribute to mood disorders and suicidal thoughts, especially in people with reduced dopamine function, known as hypodopaminergia.
Warning from Experts
Despite the positive clinical outcomes often reported with GLP-1 agonists, the researchers warn of their potential risks. Alireza Sharafshah, a PhD candidate at the Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences in Iran, cautioned against overlooking the dangers associated with these drugs. Senior author Dr. Kenneth Blum, a Research Professor at Western University Health Sciences and Ariel University, urged caution, saying, “We cannot ignore this study. We need to prevent a tragic wave of ‘people dying to lose weight.’
Dr. Mark S. Gold, a leading expert in addiction psychiatry and co-author of the study, also stressed the importance of reconsidering the widespread use of GLP-1 receptor agonists. “This research provides critical evidence for re-evaluating these drugs. The FDA and other regulatory agencies need to carefully review our findings,” he said.
Growing Global Concerns
Professor Albert Pinhasov, Provost of Ariel University, echoed these concerns, noting that while there are short-term benefits to GLP-1 agonists, the potential risks highlighted in the study warrant further investigation. The European Medicines Agency (EMA) has already launched a review of these drugs after reports of suicidal thoughts and other psychiatric side effects. Co-author Dr. Kai Uwe Lewandowski, a Professor of Surgery at the University of Arizona, noted that depression was the most commonly reported adverse effect, followed by anxiety and suicidal ideation. He stressed the need for more research to protect public health.
The Need for Genetic Testing
The study advocates for a personalized approach to prescribing GLP-1 receptor agonists, including genetic testing to assess an individual’s dopamine function before treatment. Professor Panayotis K. Thanos from Buffalo University emphasized the importance of using genetic testing tools to evaluate a patient’s risk profile. “Before prescribing GLP-1 receptor agonists, it would be wise to assess a patient’s dopamine function and addiction risk,” he said.
Caution and Vigilance
Professor Igor Elman of Harvard University reminded clinicians to remain cautious when prescribing these drugs. “While GLP-1 receptor agonists show promise for treating addictive and behavioral disorders, we must be vigilant about their potential risks,” he said. “This study is not meant to diminish the hope these drugs offer, but to ensure they are not over-prescribed.”
The study serves as an important reminder that while GLP-1 receptor agonists offer significant health benefits, their potential risks—particularly related to mental health—require careful consideration. Researchers call on regulatory agencies like the FDA and EMA to monitor these drugs closely and urge doctors to balance their benefits with caution.
The findings also highlight the need for further research to better understand the genetic factors at play and improve patient safety.
