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

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.

Disrupted sleep and risk of depression in later life: A prospective cohort study with extended follow up and a systematic review and meta-analysis.

BACKGROUND: Sleep difficulties increase the risk of current and future depression, but it is unclear if this relationship is causal. METHODS: Prospective cohort study of a community sample of men aged 70-89 years followed for up to 17 years. Initial assessments occurred between 2001 and 2004. Participants were followed until death or 31 December 2018. Patient Health Questionnaire (PHQ-9) ≥ 10 at subsequent waves of assessments (every 2-3 years) or the recorded diagnosis of a depressive disorder in the Western Australian Data Linkage System marked the onset of depression during follow up. We excluded from follow up men with prevalent depression. The systematic review of longitudinal studies examining the association between disrupted sleep and depression in later life followed PRISMA guidelines. RESULTS: 3441 of 5547 older men reported sleep difficulties at study entry. Current or past depression affected 437 of 5547 participants. Of the 4561 older men free of depression, 2693 reported sleep difficulties. The hazard ratio (HR) of incident depression among participants with sleep problems was 1.67 (95%CI = 1.39-2.00). Statistical adjustments for age, place of birth, education, smoking and physical frailty did not change the effect-size of this association. The systematic review identified another 14 studies, and the meta-analysis yielded an overall risk ratio of depression of 1.82 (95%CI = 1.69-1.97), although the overall quality of available evidence was sub-optimal. CONCLUSIONS: Disrupted sleep increases the risk of depression in later life and this seems unlikely to be due to reverse causality. Older adults with sleep difficulties are legitimate targets of interventions to prevent depression.