Prescription Sequence Symmetry Analysis of Glucagon-Like Peptide-1 Receptor Agonists and Neuropsychiatric Conditions.
GLP-1RA use may be linked to a lower chance of starting antidepressants and medications for substance use disorder, but further research is needed to understand these associations better.
Where it sits
this study against the rest of the dulaglutide corpusSummary and findings
This study examined associations between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and neuropsychiatric medication initiation in a real-world setting. Among 2,033 individuals, dulaglutide was used by 21.9%. The study found that GLP-1RA initiation was inversely associated with the initiation of antidepressants and medications for substance use disorder (SUD).
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and weight management. However, conflicting evidence from preclinical, clinical, and pharmacovigilance studies suggests potential neuropsychiatric effects. This study examined associations between GLP-1RA use and initiation of a range of neuropsychiatric medications using real-world prescription data. A Prescription Sequence Symmetry Analysis was conducted using Australia's Pharmaceutical Benefits Scheme 10% random sample between July 1, 2013 and December 31, 2024. Individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication were included. Outcomes comprised antidepressants, medication for substance use disorder (SUD), antipsychotics, psychostimulants, antidementia medications, antiparkinsonian medications, antiepileptics, and antimigraine agents. Adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using a one-year exposure window, with sensitivity analyses varying various time windows. Among 2,033 individuals, semaglutide was the most common GLP-1RA (50.6%), followed by exenatide (27.5%) and dulaglutide (21.9%). GLP-1RA initiation was inversely associated with initiation of antidepressants (aSR: 0.85; 95% CI: 0.76-0.94) and medications for SUD (aSR: 0.70; 95% CI: 0.51-0.88). No significant associations were observed for other neuropsychiatric outcomes. GLP-1RA use was inversely associated with subsequent initiation of antidepressants and medications for SUD, while no associations were identified for other neuropsychiatric marker medications. These findings highlight the need for further studies to clarify the nature and magnitude of these potential neuropsychiatric associations with GLP-1RAs.
Background
This paper addresses the potential neuropsychiatric effects associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs), which are commonly prescribed for type 2 diabetes and weight management. Previous studies have reported conflicting evidence regarding these effects, highlighting a gap in understanding the relationship between GLP-1RA use and neuropsychiatric medication initiation. This study is significant as it utilizes real-world prescription data to explore these associations.
Methods
A Prescription Sequence Symmetry Analysis was conducted using a 10% random sample from Australia's Pharmaceutical Benefits Scheme between July 1, 2013, and December 31, 2024. The study included individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication, with outcomes including various classes of neuropsychiatric medications. Adjusted sequence ratios (aSRs) were calculated using a one-year exposure window.
Results
Among 2,033 individuals, GLP-1RA initiation was inversely associated with the initiation of antidepressants (aSR: 0.85; 95% CI: 0.76-0.94) and medications for substance use disorder (aSR: 0.70; 95% CI: 0.51-0.88). No significant associations were found for other neuropsychiatric outcomes. The most common GLP-1RA was semaglutide at 50.6%.
Interpretation
The findings suggest that GLP-1RA use may be associated with a lower likelihood of initiating antidepressants and medications for substance use disorder. However, the effect sizes, while statistically significant, may not be clinically meaningful. Limitations such as reliance on prescription data and the need for further studies to confirm these associations should be considered when interpreting the results.
Key findings
- aSR: 0.85; 95% CI: 0.76-0.94 for antidepressants initiation.
- aSR: 0.70; 95% CI: 0.51-0.88 for medications for substance use disorder initiation.
- semaglutide was the most common GLP-1RA at 50.6%, followed by exenatide at 27.5% and dulaglutide at 21.9%.
- No significant associations were observed for other neuropsychiatric outcomes.
Limitations
- Not reported in abstract.
- Relies on prescription data, which may not capture all neuropsychiatric conditions.
- Further studies needed to clarify associations.