Retrospective chart review on psychiatric manifestations of GLP-1 agonist usage

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes mellitus and obesity. Beyond metabolic effects, GLP-1 signaling influences central pathways involved in mood, reward, and stress regulation, raising interest in possible psychiatric implications.

We conducted a retrospective chart review of adults (≥18 years) prescribed GLP-1 RAs at a private university hospital between January 2021 and April 2024. Demographic, medication, and psychiatric data were extracted from electronic health records. Primary outcomes included stability, improvement, worsening, or new onset of psychiatric disorders during treatment.

Among 226 patients (mean age 53.5 years; 66.8 % female; mean BMI 33.6 kg/m²), semaglutide was most frequently prescribed (73 %). The mean treatment duration was 20.2 months, with an average 6.7 % weight loss. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were most prevalent (68.6 % and 65.9 % of patients, respectively). Most remained stable (MDD: 73.6 %; GAD: 78.5 %). New-onset MDD occurred in 9.0 % and GAD in 8.7 % of affected patients, with mean latencies of 15.8 and 16.8 months, respectively. Adjustment disorder, ADHD, and insomnia also emerged in a subset, with ADHD showing the shortest latency to onset (7.8 months). Rare new-onset alcohol use disorder, trichotillomania, and opioid use disorder were observed.

GLP-1 RAs appear psychiatrically well-tolerated for most patients, though new-onset or worsening symptoms occur in a minority, underscoring the need for monitoring, particularly in high-risk populations. Prospective studies are warranted to clarify causality, mechanisms, and potential therapeutic roles in psychiatric care.