The Impact of GLP-1 Receptor Agonists (GLP-1 RAs) on Mental Health: A Systematic Review

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for managing metabolic disorders such as type 2 diabetes mellitus (T2DM) and obesity. Beyond their metabolic benefits, GLP-1 RAs exhibit neuroprotective and psychotropic effects, potentially benefiting mental health conditions like depression and anxiety. This systematic review aims to synthesize existing evidence on the effects of GLP-1 RAs on mental health outcomes, including both potential therapeutic benefits across various psychiatric disorders and the risk of associated adverse mental health effects. This systematic review was conducted across PubMed/MEDLINE and Web of Science. Inclusion criteria encompassed human and animal studies examining the impact of GLP-1 RAs on mental health. Data from 81 selected studies were extracted and analyzed, focusing on mental health outcomes and reported adverse effects. GLP-1 RAs exhibit potential beneficial effects on depressive symptoms, cognitive function, and reduced risk of suicidal ideation in animal and human models through antioxidative, anti-inflammatory mechanisms, and modulation of neurotransmitter pathways. Additionally, GLP-1 RAs were effective in reducing alcohol and substance use and binge eating behaviors. Adverse psychiatric effects associated with GLP-1 RAs, including depression, anxiety, and suicidal ideation, are noted in pharmacovigilance analyses, with variations among different GLP-1 RAs. GLP-1 RAs hold promise for addressing psychiatric conditions such as depression, anxiety, alcohol and substance use disorders. Despite their potential benefits, the risk of psychiatric adverse effects requires cautious administration.