GLP-1 receptor agonists linked to reduced suicidal ideation in adolescents with obesity | Image Credit: © 9dreamstudio - © 9dreamstudio - stock.adobe.com.

Findings from a recent study suggested that treatment with glucagon-like peptide 1 receptor agonists (GLP-1s) in adolescents with obesity is associated with lower risks of suicidal ideation or attempts. The study findings, published in JAMA Pediatrics, highlight the need for additional studies to further explore the underlying reasoning for this demonstrated association.¹

Background

According to the study investigators, Liya Kerem, MD, MSc, and Joshua Stokar, MD, GLP-1s have been increasingly used to treat obesity in adolescents. The authors sought to determine how this treatment could impact suicidal ideation and suicide attempts in this patient population.¹

Per data published in The Lancet, childhood obesity currently impacts over 124 million children and adolescents across the globe, with the prevalence of obesity among children aged 5 to 19 years having increased 8-fold in the last 40 years.^1,2

"The neuropsychiatric outcomes associated with GLP1R are not well established, and, to our knowledge, have not been examined exclusively in adolescents," stated the authors. "While some studies in adults suggest that GLP1R may have protective effects against depression, other case reports have suggested a potential association between GLP1R and new-onset depression, and a post hoc analysis suggested increased suicidal ideation."¹

The investigators conducted a propensity score-matched analysis by using a multi-institutional federated health care network to evaluate risks for suicidal ideation or attempts, after exposure to GLP-1s in adolescents with obesity.¹

Study details and results

The study authors used the incidence of suicidal ideation or attempts among adolescents identified in the study based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes recorded in patient electronic health records during 12 months of follow-up.¹

Upper respiratory tract infections (URTI) were used as negative control outcomes and gastrointestinal symptoms (GI) were used as positive control outcomes, according to the study.¹

In all, 4052 adolescents with obesity and a concomitant antiobesity intervention were identified for the GLP-1 cohort, while 50,112 were identified for the control cohort. Propensity score matching resulted in 3456 participants in each balanced cohort. Over 12 months of follow-up, GLP-1 prescription was associated with a 33% reduction of risk for suicidal ideation or attempts (1.45% vs 2.26%; hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). In addition, a higher rate of GI symptoms were observed in the prescription GLP-1 cohort (6.9% vs 5.4%; HR, 1.41; 95% CI, 1.12-1.78; P = .003), however there were no differences in rates of URTI between groups.¹

Conclusion

Overall, decreased risk for suicidal ideation was observed in the large multicenter cohort study among adolescents with obesity who were prescribed GLP-1s, "compared with matched patients not prescribed [GLP-1s] who were treated with lifestyle intervention," wrote the study investigators, suggesting a favorable psychiatric safety profile of GLP-1s in adolescents.¹

"The detected reduction in [hazard ratios] for suicidal ideation among adolescents with obesity prescribed GLP1R suggests potential avenues for future research."¹

References:

1. Kerem L, Stokar J. Risk of Suicidal Ideation or Attempts in Adolescents With Obesity Treated With GLP1 Receptor Agonists. JAMA Pediatr. Published online October 14, 2024. doi:10.1001/jamapediatrics.2024.3812

2. Collaboration NCDRF; NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627-2642. doi:10.1016/S0140-6736(17)32129-3