medwireNews: Glucagon-like peptide (GLP)-1 receptor agonist therapy may reduce the risk for suicidal ideation and attempt in teenagers with obesity compared with lifestyle intervention, suggest study findings published in JAMA Pediatrics.
“These results suggest a favorable psychiatric safety profile of [GLP-1 receptor agonists] in adolescents,” say Liya Kerem and Joshua Stokar, both from Hadassah University Medical Center in Jerusalem, Israel.
The authors collated information for 4052 patients aged 12–18 years with obesity who were given semaglutide or liraglutide between December 2019 and June 2024, and 50,112 patients who instead received a lifestyle intervention. In total, 3456 of each cohort were propensity score matched for age, sex, race, ethnicity, BMI, pre-existing mental and behavioral disorders including substance abuse, and anti-obesity and psychiatric medication use.
The patients were registered with one of 120 healthcare organizations in the USA or Europe, and before propensity score matching adolescents given a GLP-1 receptor agonist were more likely than those following lifestyle interventions to be older (mean 15.5 vs 14.7 years) and female (59 vs 49%). They also had a higher BMI (mean 41.9 vs 33.8 kg/m2), and were more likely to have diabetes (40 vs 4%) or a psychiatric disorder, such as a mood disorder (17 vs 9%), and to have used psychiatric medications, such as an antidepressant (18 vs 7%).
After 12 months of follow-up, 1.4% of adolescents given a GLP-1 receptor agonist had a diagnosis of suicidal ideation or attempt versus 2.3% of controls, giving a significant hazard ratio (HR) of 0.67.
GLP-1 receptor agonist use was also associated with a significantly higher rate of the positive control outcome of gastrointestinal symptoms than the lifestyle interventions (6.9 vs 5.4%, HR=1.41) but significantly fewer reports of acute pancreatitis (0.3 vs 0.7%). There was no significant difference in the rate of the negative control outcome of upper respiratory tract infection (10.3 vs 10.9%).
Subgroup analyses based on sex, race, ethnicity, type of GLP-1 receptor agonist, and diabetes diagnosis did not show a relationship between GLP-1 receptor agonist use and risk for suicidal ideation or attempt over up to 3 years of follow-up, Kerem and Stokar emphasize.
“The observational retrospective nature of our study design precludes drawing causal inferences,” the authors explain.
However, they believe that “the detected reduction in HRs for suicidal ideation among adolescents with obesity prescribed [GLP-1 receptor agonists] suggests potential avenues for future research.”
The researchers suggest that this relationship may be linked to a reduction in obesity leading to an improvement in quality of life and a reduced risk for psychiatric disorders, or a direct impact of GLP-1 receptor agonists on “depression-related neuropathology.”
They add: “Preclinical research indicates that [GLP-1 receptor agonists] may reduce the consumption of alcohol and other substances of abuse by modulating dopaminergic reward pathways and central γ-aminobutyric acid neurotransmission. Therefore, it is plausible that [GLP-1 receptor agonists] could mitigate suicidal ideation by affecting neurocircuitry associated with food addiction.”
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