Semaglutide Injection, a GLP1 Agonist, Induced Depression and First Time Suicidal Ideation in a Female with Long-standing Anxiety

Mental illness affects approximately one in five children in the United States, with many individuals experiencing comorbid psychiatric conditions such as anxiety, depression, and substance use disorders.Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for generalized anxiety disorder, while benzodiazepines and certain SNRIs serve as second-line options.Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and weight management, have recently raised concerns due to their emerging neuropsychiatric side effects.Recent research has shown that GLP-1RAs modulate functional connectivity in key brain networks involved in mood regulation, including the default mode, salience, and frontoparietal networks.Adverse psychiatric outcomes such as mood instability, anxiety, and suicidal ideation have been reported in post-marketing surveillance and case studies, prompting regulatory review.This case report presents a 58-year-old female with a long history of anxiety who experienced a severe psychiatric decline, including insomnia, weight loss, and suicidal ideation, following semaglutide use for weight loss.Despite multiple medication trials, only repetitive transcranial magnetic stimulation (rTMS) achieved sustained symptom relief.The patient retrospectively attributed her decline to GLP-1 agonist exposure, describing the experience as traumatic.While most large-scale studies have not shown significant increases in suicidality with GLP-1RA use, growing evidence suggests the importance of pre-treatment psychiatric screening and genetic vulnerability assessment.This case underscores the potential for adverse neuropsychiatric outcomes in vulnerable individuals and supports the call for more rigorous investigation into the central effects of GLP-1RAs and personalized approaches to prescribing these medications.