{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:06:56Z","timestamp":1768565216204,"version":"3.49.0"},"posted":{"date-parts":[[2023,8,16]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":40,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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 the risk of psychosis in humans is unknown.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This observational-cohort study used electronic health record data from 818 individuals at clinical high-risk for psychosis (CHR-P) to investigate whether BDZ exposure (including hypnotics e.g., 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    567 CHR-P individuals were included after data cleaning (105 BDZ-exposed, 462 BDZ-unexposed). 306 (54%) individuals were male, and the mean age was 22.3 years (SD 4.9). The BDZ-exposed and BDZ-unexposed 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;\n                    <jats:italic>P<\/jats:italic>\n                    =0.037), psychiatric hospital admission (HR=1.93; 95%CI:1.13-3.29;\n                    <jats:italic>P<\/jats:italic>\n                    =0.017), home visit (HR=1.64; 95%CI:1.18-2.28;\n                    <jats:italic>P<\/jats:italic>\n                    =0.004), and A&amp;E attendance (HR=1.88; 95%CI:1.31-2.72;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001). However, after controlling for confounding-by-indication through PSM, BDZ exposure did not modulate the risk of any outcomes (all\n                    <jats:italic>P<\/jats:italic>\n                    &gt;0.05). In analysis restricted to antipsychotic-na\u00efve individuals, BDZ exposure\n                    <jats:italic>reduced<\/jats:italic>\n                    the risk of transition to psychosis at trend-level (HR=0.59; 95%CI:0.32-1.08;\n                    <jats:italic>P<\/jats:italic>\n                    =0.089).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>BDZ exposure in CHR-P individuals was not associated with a reduction in the risk of psychosis transition or other adverse clinical outcomes. Results in the whole-unmatched sample suggest BDZ prescription may be more likely in CHR-P individuals with higher symptom severity.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.08.15.23294108","type":"posted-content","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T01:05:19Z","timestamp":1692234319000},"source":"Crossref","is-referenced-by-count":1,"title":["Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6582-2545","authenticated-orcid":false,"given":"Nicholas R.","family":"Livingston","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"De Micheli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-2566","authenticated-orcid":false,"given":"Robert","family":"McCutcheon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Butler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa","family":"Hamdan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony 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