Mental health outcomes in obesity interventions with GLP-1 receptor agonists: is it similar to other obesity interventions? A narrative review with systematic evidence synthesis.

Obesity is a chronic, debilitating condition with complex biological, psychosocial, and behavioral underpinnings. While the cardiometabolic consequences are reasonably well-established, the often-forgotten bidirectional association between obesity and mental health disorders, including anxiety, eating disorders, depression, and even suicidal ideations, is rarely assessed as a primary endpoint in obesity intervention studies. Similarly, documents summarizing and comparing various types of obesity interventions and their effects of mental health in this rapidly evolving field are scarce. This narrative review synthesizes the evidence on the psychological impact of lifestyle, pharmacological, and surgical interventions in the treatment of obesity. Special focus is placed on glucagon-like peptide-1 (GLP-1) receptor agonists, given their rising global use and emerging concerns regarding mental health safety. A thorough literature review was conducted across the MEDLINE, Embase, and Cochrane databases, focusing on meta-analyses, systematic reviews, and clinical trials published up to June 2025. Studies examining psychological outcomes in patients undergoing lifestyle modifications, pharmacotherapy, or bariatric surgery for weight loss were included. Mental health domains considered included quality of life, anxiety, depression, and suicidality. Due to the vast array of obesity interventions and the broad nature of mental health in the literature, this review was conducted to provide a narrative summary. Behavioral interventions consistently showed no harm to mental health and demonstrated modest improvements in depression and mental health-related quality of life. Bariatric surgery was associated with short-to-medium-term reductions in depressive and anxiety symptoms, though long-term benefits were attenuated, with some studies reporting increased suicidality after five years. Pharmacotherapies, including orlistat, bupropion/naltrexone, and phentermine/topiramate, showed mixed psychiatric impacts. The GLP-1 receptor agonists (Semaglutide, liraglutide, Tirzepatide) have shown an improvement in patient-reported mental wellbeing in several trials. Concerningly, pharmacovigilance data initially suggested a possible link with suicidality; however, subsequent robust cohort studies and meta-analyses have refuted this association. Mental health is a critical yet underprioritized element of obesity management. The current evidence suggests that most weight loss interventions are psychologically safe or beneficial, but long-term data remain limited, particularly for GLP-1 receptor agonists. Future randomized trials must incorporate mental health as a prespecified outcome, and individualized treatment approaches should integrate psychological support to optimize long-term outcomes. This review has summarized, side-by-side, the various outcomes of obesity interventions on mental health.