Impact of Glucagon-Like Peptide-1 Receptor Agonists on Mental Health: A Systematic Review of Psychiatric Safety and Antidepressant Potential.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for type 2 diabetes mellitus (T2DM) and obesity, but concerns about their mental health effects have been raised. Early safety reports linked them to suicidal thoughts and worsening depression; however, evidence remained mixed and unclear. A systematic search was conducted across three databases for studies published between 2021 and May 2026. Out of 617 records identified, 11 studies were finally included after quality checks using appropriate appraisal tools based on study design. This review was not prospectively registered. Data from over 4.9 million patients across eleven primary studies showed that GLP-1RAs did not increase psychiatric risk overall. Ten out of eleven primary studies confirmed either safety or protective psychiatric effects. Increased psychiatric risk was seen in one obesity-specific study; this may partly reflect surveillance or detection bias, though this was not directly tested. Only one of the 11 included studies directly measured mood using validated questionnaires and found that semaglutide was associated with lower (better) depression and anxiety scores. GLP-1 receptor agonists appear to maintain a safe neuropsychiatric profile, with an emerging signal that mood may benefit, currently limited to a single scale-based study among those formally included; most existing evidence remains diagnostic-code-based rather than scale-based. For T2DM patients with stable mood disorders, there is no justification for withholding these medications. For weight management, clinicians may consider baseline mental health screening before starting treatment. Future research must use validated continuous mood rating tools rather than administrative diagnostic codes to properly measure psychological benefits.