GLP-1 receptor agonists use linked to increased antidepressant use: Study

The researchers revealed that individuals exposed to GLP-1 receptor agonists face a greater risk of being dispensed antidepressants. The possible impact of GLP-1 receptor agonists on the mood of consumers requires further research and ongoing vigilance. The study was published online in Diabetes, Obesity and Metabolism on April 23, 2024.

Glucagon-like peptide-1 receptor agonists, commonly prescribed for managing type 2 diabetes mellitus (T2DM), have garnered attention for their potential benefits beyond glycemic control. These agents have been associated with cardiovascular risk reduction, weight loss, and even neuroprotective effects, prompting investigations into their broader therapeutic implications.

Osvaldo P. Almeida from the Institute for Health Research in the University of Notre Dame, Fremantle, Western Australia, Australia, and colleagues aimed to determine if the dispensing of GLP-1 receptor agonists is associated with increased dispensing of antidepressants.

For this purpose, the researchers used case-control, cross-sectional, and retrospective cohort study designs to investigate the association between dispensed GLP-1 receptor agonists and antidepressants between 2012 and 2022 in the 10% random Australian Pharmaceutical Benefits Scheme (PBS) data sample.

PBS-listed GLP-1 receptor agonists, dulaglutide, exenatide, and semaglutide were the exposures. Outcomes were the odds ratio and hazard ratio of being dispensed any antidepressant. Analyses were adjusted for demographic measures and medicines dispensing to manage cardiovascular diseases or insomnia/anxiety.

The study led to the following findings:

• 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); 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).
• 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.
• Additional analyses restricting the exposure time confirmed these associations for all PBS-listed GLP-1 receptor agonists.

Analysis of the 10% PBS database revealed that individuals dispensed GLP-1 RAs would probably be dispensed antidepressants. The strength of the association between GLP-1 RAs and antidepressants was like that of insulin, weaker associations were also noticed for sulphonylureas, biguanides, and dipeptidyl peptidase 4 inhibitors.

The researchers found the association between GLP-1 RAs and antidepressants to be consistent, largely independent of the class of antidepressant dispensed and study design, however, the results could have been affected by the detection and prescription biases and confounding factors.

"The study findings reinforce the need for ongoing vigilance and further research about the possible mental health consequences of exposure to GLP-1 RAs," they concluded.

Reference:

Almeida OP, Fong Z, Hill Almeida LM, Sanfilippo FM, Page A, Etherton-Beer C. Cross-sectional, case-control and longitudinal associations between exposure to glucagon-like peptide-1 receptor agonists and the dispensing of antidepressants. Diabetes Obes Metab. 2024 Apr 23. doi: 10.1111/dom.15616. Epub ahead of print. PMID: 38650544.