GLP1 agonists linked to depression risk in a new genetic study

GLP1 agonists linked to depression risk in a new genetic study

A groundbreaking study published in the journalCurrent neuropharmacologyshows a potential link between glucagon-like peptide-1 (GLP1) receptor agonists used in blockbuster drugs such as Ozempic and the risk of depression and suicidal ideation (SI). Using advanced computational pharmacogenomic analysis, the international team of 24 researchers uncovered genetic pathways that can induce depressive phenotypes in users of GLP1 agonists, raising significant concerns about the safety of these drugs for certain individuals.

The study, led by researchers in the United States, Brazil, Iran and Israel, shows that GLP1 agonists, however, benefit individuals with hyperdopaminergia (excess dopamine activity) but may have harmful effects on those with hypodopaminergia (low dopamine function). The authors found genetic associations between GLP1 receptor agonists and genes such as DRD3, BDNF and CREB1, which are involved in mood regulation and reward pathways. Their results suggest that chronic use of these medications may dysregulate dopamine signaling, potentially leading to depressive symptoms, mood disorders, and SI.

Warning voices from experts

While the idea of ​​induction of depression and SI from GLP1 agonism is controversial with both the negative and positive reporting based on the findings presented in this article by Alireza Sharafshah, PhD thesis from Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran, Prediction against Promoter Stimulation by Molecular Research Center.

This study should not be ignored despite the hype surrounding the positive clinical results of GLP1 receptor agonists. We urge the clinical prescribing community to proceed with caution to avoid another tragic wave of “people losing weight to lose weight.” “

Dr. Kenneth Blum, senior author, research professor at Western University Health Sciences and Ariel University

Dr. Mark S. Gold, a pioneer and co-author of Addiction Psychiatry, emphasized: "The paper provides critical evidence for reassessing the widespread use of GLP1 receptor agonists. The FDA and other regulatory agencies should carefully consider our findings when labeling and monitoring these drugs."

Rising global concerns

Professor Albert Pinhasov, Provost of Ariel University, echoed these sentiments, stating: "While there are encouraging short-term benefits of GLP1 receptor agonists, we must recognize the potential risks highlighted in this study. These findings should encourage regulators and clinicians to investigate further as the heterogeneity of the human population continues to persist."

The European Medicines Agency (EMA) has already initiated a review of GLP1 agonists following reports of suicidal ideation and other psychiatric adverse events. Co-author Dr. Kai Uwe Lewandowski, professor of surgery at the University of Arizona Medical School of Medicine, noted: "Depression was the most commonly reported adverse event associated with these medications, followed by anxiety and suicidal ideation. Our results strongly support the need for further investigation to ensure public health."

The role of genetic testing

The study advocates personalized medicine approaches, including genetic testing for hypodopaminergia, to identify risks before prescribing GLP1 receptor agonists. Professor Panayotis K. Thanos of the University of Buffalo commented: "Before prescribing GLP1 receptor agonists, it would be prudent to use genetic testing tools to assess a patient's dopamine function and addiction risk profile."

Balancing hope with vigilance

Professor Igor Elman of Harvard University warned: "While GLP1 receptor agonists promise to treat addictive and behavioral disorders, we must remain vigilant about their potential harm. This study is not intended to burst the bubble of hope, but to add a layer of caution in their over-prescription."

About the study

The article with the title“In Silico Pharmacogenomic Assessment of Glucagon-like Peptide-1 (GLP1) Agonists and Genetic Addiction Risk Score (GARS) Related Pathways: Effects on Suicidal Ideation and Substance Use Disorder,”Provides a detailed map of the genetic pathways involved in these risks. The study serves as a critical reminder that while these drugs may provide significant health benefits, their potential risks warrant careful consideration and further research.

Diploma

This cross-cultural research study provides essential insights that could save lives. It calls on regulators like the FDA and EMA to closely monitor these drugs and urges clinicians to balance their benefits with caution.

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