Prescription Sequence Symmetry Analysis of Glucagon-Like Peptide-1 Receptor Agonists and Neuropsychiatric Conditions.

Alfonso Arvez MJ, Wade S, Goordeen D, Ilomäki J, Cross AJ, Langiu M, Tan GSQ

Clinical pharmacology and therapeutics30 Jul 2026

PMID42533561PMCIDPMC13424737DOI10.1002/cpt.70414PepBankPUB-42533561

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

01HumanNot a test of Semaglutide aloneObservational studyOther
In Australian prescription database analysis, pooled GLP-1RA initiation including semaglutide was inversely associated with antidepressant initiation.
In plain wordsDatabase analysis linked pooled GLP-1RA initiation, including semaglutide, to less subsequent antidepressant initiation relative to the reverse prescription sequence.
Peptide
Semaglutide
Outcome
DecreaseAntidepressant initiation
Study
n: not reported in source
Comparator
reverse prescription sequence
Outcome group
Anxiety and mood · Mental health and mood
Measurements
Adjusted sequence ratio
0.85 aSR
GLP-1RA initiation and antidepressant initiation
95% CI of aSR
0.76 to 0.94 aSR
GLP-1RA initiation and antidepressant initiation
Source sentences
Summary
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).
3 context sentences(design, population, supporting numbers)
Summary · context
A Prescription Sequence Symmetry Analysis was conducted using Australia's Pharmaceutical Benefits Scheme 10% random sample between July 1, 2013 and December 31, 2024.
Summary · context
Individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication were included.
Summary · context
Adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using a one-year exposure window, with sensitivity analyses varying various time windows.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4253356101
02HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyOther
In Australian prescription database analysis, pooled GLP-1RA initiation including dulaglutide was inversely associated with antidepressant initiation.
In plain wordsDatabase analysis linked pooled GLP-1RA initiation, including dulaglutide, to less subsequent antidepressant initiation relative to the reverse prescription sequence.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseAntidepressant initiation
Study
Homo sapiensn: not reported in source
Individuals with incident GLP-1RA and neuropsychiatric medication dispensing in Australia's Pharmaceutical Benefits Scheme
Comparator
reverse prescription sequence
Outcome group
Anxiety and mood · Mental health and mood
Measurements
Adjusted sequence ratio
0.85 ratio
pooled GLP-1RA initiation, antidepressant initiation
aSR 95% CI
0.76 to 0.94 ratio
pooled GLP-1RA initiation, antidepressant initiation
Source sentences
Summary
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).
3 context sentences(design, population, supporting numbers)
Summary · context
A Prescription Sequence Symmetry Analysis was conducted using Australia's Pharmaceutical Benefits Scheme 10% random sample between July 1, 2013 and December 31, 2024.
Summary · context
Individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication were included.
Summary · context
Adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using a one-year exposure window, with sensitivity analyses varying various time windows.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Show in the study text Report a problemFND-4253356102
03HumanNot a test of Semaglutide aloneObservational studyOther
In Australian prescription database analysis, pooled GLP-1RA initiation including semaglutide was inversely associated with substance use disorder medication initiation.
In plain wordsDatabase analysis linked pooled GLP-1RA initiation, including semaglutide, to less subsequent substance use disorder medication initiation relative to the reverse sequence.
Peptide
Semaglutide
Outcome
DecreaseSubstance use disorder medication initiation
Study
n: not reported in source
Comparator
reverse prescription sequence
Outcome group
Anxiety and mood · Mental health and mood
Measurements
Adjusted sequence ratio
0.7 aSR
GLP-1RA initiation and substance use disorder medication initiation
95% CI of aSR
0.51 to 0.88 aSR
GLP-1RA initiation and substance use disorder medication initiation
Source sentences
Summary
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).
3 context sentences(design, population, supporting numbers)
Summary · context
A Prescription Sequence Symmetry Analysis was conducted using Australia's Pharmaceutical Benefits Scheme 10% random sample between July 1, 2013 and December 31, 2024.
Summary · context
Individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication were included.
Summary · context
Adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using a one-year exposure window, with sensitivity analyses varying various time windows.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4253356103
04HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyOther
In Australian prescription database analysis, pooled GLP-1RA initiation including dulaglutide was inversely associated with substance use disorder medication initiation.
In plain wordsDatabase analysis linked pooled GLP-1RA initiation, including dulaglutide, to less subsequent substance use disorder medication initiation relative to the reverse sequence.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseSubstance use disorder medication initiation
Study
Homo sapiensn: not reported in source
Individuals with incident GLP-1RA and neuropsychiatric medication dispensing in Australia's Pharmaceutical Benefits Scheme
Comparator
reverse prescription sequence
Outcome group
Anxiety and mood · Mental health and mood
Measurements
Adjusted sequence ratio
0.7 ratio
pooled GLP-1RA initiation, substance use disorder medication initiation
aSR 95% CI
0.51 to 0.88 ratio
pooled GLP-1RA initiation, substance use disorder medication initiation
Source sentences
Summary
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).
3 context sentences(design, population, supporting numbers)
Summary · context
A Prescription Sequence Symmetry Analysis was conducted using Australia's Pharmaceutical Benefits Scheme 10% random sample between July 1, 2013 and December 31, 2024.
Summary · context
Individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication were included.
Summary · context
Adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using a one-year exposure window, with sensitivity analyses varying various time windows.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Show in the study text Report a problemFND-4253356104
05HumanNot a test of Semaglutide aloneObservational studyOther
In Australian prescription database analysis, pooled GLP-1RA initiation including semaglutide showed no significant associations with other neuropsychiatric medication outcomes.
In plain wordsDatabase analysis found no significant associations for other neuropsychiatric medication outcomes with pooled GLP-1RA initiation, including semaglutide.
Peptide
Semaglutide
Outcome
No significant changeOther neuropsychiatric medication outcomes
Study
n: not reported in source
Comparator
reverse prescription sequence
Outcome group
Anxiety and mood · Mental health and mood
Source sentences
Summary
No significant associations were observed for other neuropsychiatric outcomes.
4 context sentences(design, population, supporting numbers)
Summary · context
Outcomes comprised antidepressants, medication for substance use disorder (SUD), antipsychotics, psychostimulants, antidementia medications, antiparkinsonian medications, antiepileptics, and antimigraine agents.
Summary · context
A Prescription Sequence Symmetry Analysis was conducted using Australia's Pharmaceutical Benefits Scheme 10% random sample between July 1, 2013 and December 31, 2024.
Summary · context
Individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication were included.
Summary · context
Adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using a one-year exposure window, with sensitivity analyses varying various time windows.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4253356105
06HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyOther
In Australian prescription database analysis, pooled GLP-1RA initiation including dulaglutide showed no significant associations with other neuropsychiatric medication outcomes.
In plain wordsDatabase analysis found no significant associations for other neuropsychiatric medication outcomes with pooled GLP-1RA initiation, including dulaglutide.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeOther neuropsychiatric medication outcomes
Study
Homo sapiensn: not reported in source
Individuals with incident GLP-1RA and neuropsychiatric medication dispensing in Australia's Pharmaceutical Benefits Scheme
Comparator
reverse prescription sequence
Outcome group
Anxiety and mood · Mental health and mood
Source sentences
Summary
No significant associations were observed for other neuropsychiatric outcomes.
4 context sentences(design, population, supporting numbers)
Summary · context
Outcomes comprised antidepressants, medication for substance use disorder (SUD), antipsychotics, psychostimulants, antidementia medications, antiparkinsonian medications, antiepileptics, and antimigraine agents.
Summary · context
A Prescription Sequence Symmetry Analysis was conducted using Australia's Pharmaceutical Benefits Scheme 10% random sample between July 1, 2013 and December 31, 2024.
Summary · context
Individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication were included.
Summary · context
Adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using a one-year exposure window, with sensitivity analyses varying various time windows.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Show in the study text Report a problemFND-4253356106

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 3Current
22 Oct 2026, 02:25 UTC
Study results updated
Version 2
21 Oct 2026, 18:59 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Prescription Sequence Symmetry Analysis of Glucagon-Like Peptide-1 Receptor Agonists and Neuropsychiatric Conditions.

Summary

Results from this study6

Studies that did not test the peptide alone6

Version history

Subjects

Publication types

MeSH terms