may have modest antidepressant and reward-related psychiatric benefits, but their psychiatric effects remain unsettled.
Evidence
This systematic review of studies on GLP-1 receptor agonists and psychiatric outcomes found modest antidepressant signals, inconsistent findings on , possible benefit in eating and substance use disorders, and no consistent improvement in schizophrenia symptoms despite metabolic benefits.
Caveat
Interpretation is limited by heterogeneous study designs, dosing and populations, limited sample diversity, and underrepresentation of people with psychiatric comorbidities.
Simplified
This systematic review examines the current literature on glucagon-like peptide-1 receptor agonists (GLP-1RAs)-associated psychiatric manifestations, including depression, , 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.
Key numbers
195%
Increase in Major Depressive Disorder Risk
Risk associated with GLP-1RA use in individuals with obesity
0.12
Reduction in Depression Scores
Standardized mean difference from meta-analysis of GLP-1RA users
−8.14
Reduction in Binge Eating Scale Scores
Mean difference in scores among GLP-1RA users compared to controls
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