Prescription Sequence Symmetry Analysis of Glucagon-Like Peptide-1 Receptor Agonists and Neuropsychiatric Conditions.
GLP-1RA initiation may be associated with a lower likelihood of starting antidepressants and medications for substance use disorder, but further research is needed to clarify these associations.
Where it sits
this study against the rest of the exenatide corpusSummary and findings
This study examined associations between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and neuropsychiatric medication initiation using real-world prescription data. The analysis included 2,033 individuals and focused on various neuropsychiatric medications. GLP-1RA initiation was inversely associated with initiation of antidepressants and medications for substance use disorder.
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 of 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 the importance of understanding the relationship between GLP-1RA use and neuropsychiatric medication initiation. This study aims to provide insights into these associations using real-world prescription data.
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. Primary outcomes included initiation of antidepressants and medications for substance use disorder, with adjusted sequence ratios calculated over a one-year exposure window.
Results
Among 2,033 individuals, GLP-1RA initiation was inversely associated with 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 observed for other neuropsychiatric outcomes. The findings suggest a potential inverse relationship between GLP-1RA use and the initiation of specific neuropsychiatric medications.
Interpretation
The findings indicate that GLP-1RA use may be associated with a lower likelihood of initiating antidepressants and medications for substance use disorder, which contrasts with some prior literature suggesting potential neuropsychiatric risks. However, the effect sizes are relatively small and should be interpreted with caution. Limitations such as reliance on prescription data and the need for further studies to confirm these associations may affect the conclusions drawn from this analysis.
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
- semaglutide was the most common GLP-1RA (50.6%)
- exenatide accounted for 27.5% of GLP-1RA use
- dulaglutide represented 21.9% of GLP-1RA use
Limitations
- study relies on prescription data, which may not capture all relevant neuropsychiatric outcomes
- further studies are needed to clarify the nature and magnitude of associations
- observational study design limits causal inferences
- no significant associations for other neuropsychiatric medications reported