Glucagon-Like Peptide-1 Receptor Agonists in Psychiatry: A Pharmacoepidemiological Scoping Review

Pharmacoepidemiological studies have expanded the capacity to detect therapeutic benefits and adverse drug effects of medications. In the case of glucagon-like peptide-1 receptor agonists (GLP-1RAs), their fast uptake for treating diabetes and obesity has generated substantial real-world experience, facilitating exploration of benefits for additional indications. In the context of psychiatric disorders, studies based on pharmacovigilance data and large electronic health record (EHR) databases have shown that initial concerns regarding an association between suicidality and GLP-1RA use were not supported by the evidence. Emerging data also suggest potential therapeutic benefits, with the strongest evidence for substance use disorders, binge-eating disorder, and bulimia nervosa, as well as improved metabolic outcomes in patients with schizophrenia. However, randomized controlled trials are needed to determine whether such beneficial associations represent mechanistic effects, and further surveillance is needed to assess potential risks for anorexia. Also, more comprehensive EHR databases using harmonized methodologies and integrated with multimodal data will expand pharmacoepidemiology capabilities, including the use of machine learning and artificial intelligence. In this scoping review, we summarize the pharmacoepidemiologic evidence regarding the potential psychiatric effects, both therapeutic and adverse, of GLP-1RAs and the methodological and translational gaps that need to be addressed to strengthen the robustness of pharmacoepidemiologic findings and accelerate therapeutic discovery.