TY - JOUR
T1 - Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis
AU - Livingston, Nicholas R.
AU - De Micheli, Andrea
AU - McCutcheon, Robert
AU - Butler, Emma
AU - Hamdan, Marwa
AU - Grace, Anthony A.
AU - McGuire, Philip
AU - Egerton, Alice
AU - Fusar-Poli, Paolo
AU - Modinos, Gemma
N1 - This work was supported by the Wellcome Trust & The Royal Society [Sir Henry Dale Fellowship 202397/Z/16/Z to G.M.], and represents independent research partly funded by the National Institute of Health Research (NIHR) Maudsley Biomedical Researh Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. R.A.M.’s work is funded by a Wellcome Trust Clinical Research Career Development (224625/Z/21/Z). A.A.G.’s work is funded by a United States Public Health Service Grant (National Institute of Mental Health MH57440). N.R.L. is supported by a PhD studentship from the Medical Research Council Doctoral Training Partnership. For the purpose of open access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
PY - 2024/4/3
Y1 - 2024/4/3
N2 - Background and HypothesisAnimal 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 DesignThis 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 Results567 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).ConclusionsBDZ 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.
AB - Background and HypothesisAnimal 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 DesignThis 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 Results567 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).ConclusionsBDZ 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.
U2 - 10.1093/schbul/sbae036
DO - 10.1093/schbul/sbae036
M3 - Article
SN - 0586-7614
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
M1 - sbae036
ER -