Summary: A new international study reveals a possible connection between GLP1 receptor agonists—used in drugs like Ozempic—and increased risk of depression and suicidal ideation, especially in people with low dopamine function. Researchers used advanced pharmacogenomic tools to identify genetic pathways that may be vulnerable to dopamine dysregulation when exposed to these medications.
The study calls for personalized genetic screening before prescribing GLP1 drugs, especially given their rising popularity for weight loss. While these medications offer short-term benefits, the authors urge clinicians and regulators to exercise caution amid growing concerns over mental health side effects.
Key Facts:
- Genetic Risk: GLP1 receptor agonists may worsen depression in individuals with hypodopaminergia.
- Global Concern: Regulatory bodies like the EMA are reviewing these drugs after reports of suicidal thoughts.
- Call for Screening: Researchers advocate for genetic testing before prescribing to assess dopamine function risk.
Source: Bentham Science Publishers
A groundbreaking study published in the journal Current Neuropharmacology highlights a concerning potential link between Glucagon-like Peptide-1 (GLP1) receptor agonists—widely used in blockbuster drugs like Ozempic—and the risk of depression and suicidal ideation (SI).
Using advanced pharmacogenomic computational analyses, the international team of 24 researchers revealed genetic pathways that may induce depressive phenotypes in users of GLP1 agonists, raising significant concerns about the safety of these medications for certain individuals.
The study, led by researchers across the United States, Brazil, Iran, and Israel, demonstrates that while GLP1 agonists benefit individuals with hyperdopaminergia (excess dopamine activity), they may have harmful effects on individuals with hypodopaminergia (low dopamine function).
The authors found genetic associations between GLP1 receptor agonists and genes such as DRD3, BDNF, and CREB1, which are implicated in mood regulation and reward pathways.
Their findings suggest that chronic use of these drugs could dysregulate dopamine signaling, potentially leading to depressive symptoms, mood disturbances, and SI.
Cautionary Voices from Experts
While the idea of GLP1 agonism induction of depression and SI is controversial with both negative and positive reporting, based on the evidence presented in this article by Alireza Sharafshah, a PhD candidate from Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran, the authors caution against promoting chronic stimulation via GLP-1 agonists.
“This study should not be ignored, despite the hype surrounding the positive clinical outcomes of GLP1 receptor agonists,” said senior author Dr. Kenneth Blum, Research Professor at Western University Health Sciences and Ariel University.
“We urge the clinical prescribing community to proceed with caution to avoid another tragic wave of ‘people dying to lose weight.’”
Dr. Mark S. Gold, an addiction psychiatry pioneer and co-author, emphasized, “The paper provides critical evidence for re-evaluating the widespread use of GLP1 receptor agonists. The FDA and other regulatory agencies should carefully consider our findings when it comes to 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 acknowledge the potential risks highlighted in this study.
“These findings should encourage regulatory agencies and clinicians to investigate further, given the heterogeneity of the human population.”
The European Medicines Agency (EMA) has already initiated a review of GLP1 agonists following reports of suicidal thoughts and other psychiatric adverse events.
Co-author Dr. Kai Uwe Lewandowski, Professor of Surgery at the University of Arizona School of Medicine, noted, “Depression was the most commonly reported adverse event associated with these drugs, followed by anxiety and suicidal ideation. Our findings strongly support a need for further investigation to safeguard public health.”
The Role of Genetic Testing
The study advocates for personalized medicine approaches, including genetic testing for hypodopaminergia, to identify individuals at risk before prescribing GLP1 receptor agonists. Professor Panayotis K. Thanos of Buffalo University 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 hold promise for treating addictive and behavioral disorders, we must remain vigilant about their potential harm.
This study is not intended to break the bubble of hope but to add a layer of precaution in their over-prescription.”
About the Study
The article, titled “In Silico Pharmacogenomic Assessment of Glucagon-like Peptide-1 (GLP1) Agonists and Genetic Addiction Risk Score (GARS) Related Pathways: Implications for Suicide 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 medications can provide significant health benefits, their potential risks warrant careful scrutiny and further research.
Conclusion
This cross-cultural research study provides essential insights that could save lives. It urges regulatory agencies such as the FDA and EMA to monitor these drugs closely and calls on clinicians to balance their benefits with caution.
About this depression and Ozempic research news
Author: Noman Akbar
Source: Bentham Science Publishers
Contact: Noman Akbar – Bentham Science Publishers
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“In Silico Pharmacogenomic Assessment of Glucagon-like Peptide-1 (GLP1) Agonists and the Genetic Addiction Risk Score (GARS) Related Pathways: Implications for Suicidal Ideation and Substance Use Disorder” by Kenneth Blum et al. Current Neuropharmacology
Abstract
In Silico Pharmacogenomic Assessment of Glucagon-like Peptide-1 (GLP1) Agonists and the Genetic Addiction Risk Score (GARS) Related Pathways: Implications for Suicidal Ideation and Substance Use Disorder
Introduction: Glucagon-Like Peptide-1 Receptor (GLP1R) agonists have become widespread anti-obesity/diabetes pharmaceuticals in the United States.
Aim: This article aimed to provide our current knowledge on the plausible mechanisms linked to the role of Ozempic (Semaglutide), which is generalized as one of the anti-addiction compounds.
Methods: The effects of GLP1R agonists in Alcohol Use Disorder (AUD) and substance use disorder (SUD) are mediated, in part, through the downregulation of dopamine signaling.
We posit that while GLP1R agonism could offer therapeutic advantages in hyperdopaminergia, it may be detrimental in patients with hypodopaminergia, potentially leading to long-term induction of Suicidal Ideation (SI). The alleged posit of GLP1 agonists to induce dopamine homeostasis is incorrect. This study refined 31 genes based on the targets of Ozempic, GLP1R, and related enzyme
s for SI and 10 genes of the Genetic Addiction Risk Score (GARS) test. STRING-MODEL refined 29 genes, and further primary analyses indicated associations of GLP1R with DRD3, BDNF, CREB1, CRH, IL6, and DPP4.
Results: In-depth silico enrichment analysis revealed an association between candidate genes and depressive phenotypes linked with dopaminergic signaling. Finally, through primary and in-depth silico analyses, we demonstrated multiple findings supporting that GLP1R agonists can induce depression phenotypes.
Conclusion: Our findings suggest that associated polymorphisms seem to have overlapping effects with addictive behaviors of Reward Deficiency Syndrome (RDS) and dopamine regulation.
Consequently, GLP1R agonists may represent a double-edged sword, potentially triggering both antiaddictive effects and SI by exacerbating depressive phenotypes. Thus, we encourage the scientific community to perform further empirical clinical studies to confirm this proposed pathway.
