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Baseline benzodiazepine exposure is associated with greater risk of transition in clinical high-risk for psychosis (CHR-P): a meta-analysis

Published online by Cambridge University Press:  23 August 2023

Andrea Raballo Open the ORCID record for Andrea Raballo [Opens in a new window] ,
Michele Poletti Open the ORCID record for Michele Poletti [Opens in a new window]  and
Antonio Preti Open the ORCID record for Antonio Preti [Opens in a new window]
Andrea Raballo*
Affiliation:
Chair of Psychiatry, Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland Cantonal Sociopsychiatric Organisation, Mendrisio, Switzerland
Michele Poletti
Affiliation:
Department of Mental Health and Pathological Addiction, Child and Adolescent Neuropsychiatry Service, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
Antonio Preti
Affiliation:
Department of Neuroscience, University of Turin, Turin, Italy
*
Corresponding author: Andrea Raballo; Email: andrea.raballo@usi.ch
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Abstract

Background

Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics and to antidepressants in individuals at clinical high-risk for psychosis (CHR-P) have opposite prognostic effects as regards imminent transition to psychosis, with antipsychotics associated with higher risk and antidepressants associated with a lower risk in comparison to not-exposed individuals. Despite their common use, baseline exposure to benzodiazepines (BDZ) in CHR-P has surprisingly received poor attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap.

Methods

Systematic scrutiny of Medline and Cochrane library, performed up to 31 December 2022, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on BDZ baseline exposure in relation to such outcome.

Results

Of 1893 identified records, five studies were included in the systematic review and meta-analysis. The proportion of participants with exposure to BDZ at baseline ranged from 5.5% (one study) to 46.2%, with an average of 16.8%. At the end of the period of observation, i.e., the follow-up as reported in the study, 28.4% [95% confidence interval (CI) 19.7–39.1%] participants developed psychosis among the BDZ-exposed against 9.3% (7.3 to 11.9%) among the controls. CHR-P participants who were already under BDZ treatment at baseline had more than double chance of transition to psychosis than CHR-P participants who were BDZ-naïve. The risk ratio (RR) was 2.42 (95% CI 1.38–4.23) in the common effects model (z = 3.09; p = 0.002), and 2.40 (1.53 to 3.77) in the random-effects model (z = 5.40; p = 0.006; tau-squared = 0.0). There was no relevant heterogeneity: Cochran's Q = 1.49; df = 4; p = 0.828; I2 = 0.0% (95% CI 0.0–79%). Quality was good in four studies.

Conclusions

Ongoing BDZ exposure at inception in CHR-P is associated with a higher risk of transition to psychosis at follow up. This meta-analytic association, which echoes a similar effect of baseline antipsychotic exposure, plausibly indicates that the clinicians' prescription of pharmacological intervention captures some form of prognostically-relevant information (e.g. an anxiety permeated mental state requiring BDZ prescription) that are not adequately encompassed by current CHR-P categorical criteria.

Keywords

Antipsychoticsbenzodiazepinesclinical high-riskmeta-analysispsychosistransition to psychosis
Type
Review Article
Information
Psychological Medicine , Volume 53 , Issue 14 , October 2023 , pp. 6417 - 6423
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Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

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