Cross‐sectional, case‐control and longitudinal associations between exposure to glucagon‐like peptide‐1 receptor agonists and the dispensing of antidepressants

Abstract Aim To determine if the dispensing of glucagon‐like peptide (GLP)‐1 receptor agonists is associated with increased dispensing of antidepressants. Materials and Methods We used cross‐sectional, case‐control and retrospective cohort study designs to examine the association between dispensed GLP‐1 receptor agonists and antidepressants between 2012 and 2022 in the 10% random sample of the Australian Pharmaceutical Benefits Scheme (PBS) data. PBS‐listed GLP‐1 receptor agonists, exenatide, dulaglutide and semaglutide were the exposures. Outcomes were the odds ratio [ORs; 99% confidence interval (CI)] and hazard ratio (99% CI) of being dispensed any antidepressant. Analyses were adjusted for demographic measures and the dispensing of medicines to manage cardiovascular diseases or anxiety/insomnia. Statistical tests were two‐sided at the 1% level of significance. Results In total, 358 075 of 1 746 391 individuals were dispensed antidepressants, and 8495 of the 24 783 dispensed a GLP‐1 receptor agonist were also dispensed an antidepressant in 2022 (OR 1.44; 99% CI 1.38‐1.50); 24 103 of the 1 746 391 participants had been dispensed a GLP‐1 receptor agonist between 2012 and 2021, and of these 8083 were dispensed antidepressants in 2022 (OR 1.52; 99% CI 1.46‐1.59). The 2012 cohort included 1 213 316 individuals who had not been dispensed antidepressants that year. The hazard ratio of being dispensed an antidepressant between 2013 and 2022 following the dispensing of a GLP‐1 receptor agonist was 1.19 (99% CI 1.12‐1.27). Additional analyses restricting the time of exposure confirmed these associations for all PBS‐listed GLP‐1 receptor agonists. Conclusions Individuals exposed to GLP‐1 receptor agonists are at greater risk of being dispensed antidepressants. The possible impact of GLP‐1 receptor agonists on the mood of consumers requires ongoing vigilance and further research.