Psychiatric effects of GLP-1 receptor agonists: A systematic review of emerging evidence

This systematic review examines the current literature on glucagon-like peptide-1 receptor agonists (GLP-1RAs)-associated psychiatric manifestations, including depression, suicidality, eating disorders, substance use disorders (SUD) and schizophrenia spectrum disorders. A comprehensive literature search was conducted to identify studies evaluating the association between GLP-1RAs and psychiatric outcomes. The electronic databases systematically searched were PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase and Web of Science. GLP-1RAs are increasingly recognised for their potential neuropsychiatric effects beyond glycaemic control and weight loss. Findings suggest modest antidepressant effects, inconsistent associations with suicidality and potential therapeutic benefit in disorders of reward regulation. These findings are constrained by limited sample diversity, variability in outcome measures and the consistent underrepresentation of individuals with psychiatric comorbidities, factors that warrant targeted future research. This review highlights key findings on the neuropsychiatric effects of GLP-1RAs. The heterogeneity among the studies in terms of dosing, clinical indications and baseline psychiatric status complicates interpretation, but preliminary evidence suggests modest antidepressant effects and potential therapeutic roles in eating and SUD. Concerns regarding suicidality remain unresolved. In schizophrenia, GLP-1RAs provide clear metabolic benefits but have not demonstrated consistent effects on psychiatric symptomatology.