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Effects of benzodiazepine exposure on real-world clinical outcomes in individuals at clinical high risk for psychosis

Abstract:

Background and Hypothesis

Animal models indicate GABAergic dysfunction in the development of psychosis, and that benzodiazepine (BDZ) exposure can prevent the emergence of psychosis-relevant phenotypes. However, whether BDZ exposure influences real-world clinical outcomes in individuals at clinical high risk for psychosis (CHR-P) is unknown.

Study Design

This observational cohort study used electronic health record data from CHR-P individuals to investigate whether BDZ exposure (including hypnotics, eg, zopiclone) reduces the risk of developing psychosis and adverse clinical outcomes. Cox proportional-hazards models were employed in both the whole-unmatched sample, and a propensity score matched (PSM) subsample.

Study Results

567 CHR-P individuals (306 male, mean[±SD] age = 22.3[±4.9] years) were included after data cleaning. The BDZ-exposed (n = 105) and BDZ-unexposed (n = 462) groups differed on several demographic and clinical characteristics, including psychotic symptom severity. In the whole-unmatched sample, BDZ exposure was associated with increased risk of transition to psychosis (HR = 1.61; 95% CI: 1.03–2.52; P = .037), psychiatric hospital admission (HR = 1.93; 95% CI: 1.13–3.29; P = .017), home visit (HR = 1.64; 95% CI: 1.18–2.28; P = .004), and Accident and Emergency department attendance (HR = 1.88; 95% CI: 1.31–2.72; P < .001). However, after controlling for confounding-by-indication through PSM, BDZ exposure did not modulate the risk of any outcomes (all P > .05). In an analysis restricted to antipsychotic-naïve individuals, BDZ exposure reduced the risk of transition to psychosis numerically, although this was not statistically significant (HR = 0.59; 95% CI: 0.32–1.08; P = .089).

Conclusions

BDZ exposure in CHR-P individuals was not associated with a reduction in the risk of psychosis transition or adverse clinical outcomes. Results in the whole-unmatched sample suggest BDZ prescription may be more likely in CHR-P individuals with higher symptom severity.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1093/schbul/sbae036

Authors


More by this author
Role:
Author
ORCID:
0000-0002-6582-2545
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Psychiatry
Role:
Author
ORCID:
0000-0003-1102-2566
More by this author
Role:
Author
ORCID:
0000-0003-4366-3835


More from this funder
Funder identifier:
https://ror.org/029chgv08
Funding agency for:
McCutcheon, RA
Grant:
224625/Z/21/Z


Publisher:
Oxford University Press
Journal:
Schizophrenia Bulletin More from this journal
Volume:
51
Issue:
2
Pages:
446-457
Place of publication:
United States
Publication date:
2024-04-03
Acceptance date:
2024-03-27
DOI:
EISSN:
1745-1701
ISSN:
0586-7614
Pmid:
38567823


Language:
English
Keywords:
Pubs id:
1987732
Local pid:
pubs:1987732
Deposit date:
2024-04-07

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