苯二氮䓬类药物暴露对临床高危精神病个体现实世界临床结局的影响。

Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis.

作者信息

Livingston Nicholas R, De Micheli Andrea, McCutcheon Robert, Butler Emma, Hamdan Marwa, Grace Anthony A, McGuire Philip, Egerton Alice, Fusar-Poli Paolo, Modinos Gemma

机构信息

Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

出版信息

medRxiv. 2023 Aug 16:2023.08.15.23294108. doi: 10.1101/2023.08.15.23294108.

DOI:10.1101/2023.08.15.23294108

PMID:37645948

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10462200/

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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; =0.037), psychiatric hospital admission (HR=1.93; 95%CI:1.13-3.29; =0.017), home visit (HR=1.64; 95%CI:1.18-2.28; =0.004), and A&E attendance (HR=1.88; 95%CI:1.31-2.72; <0.001). However, after controlling for confounding-by-indication through PSM, BDZ exposure did not modulate the risk of any outcomes (all >0.05). In analysis restricted to antipsychotic-naïve individuals, BDZ exposure the risk of transition to psychosis at trend-level (HR=0.59; 95%CI:0.32-1.08; =0.089).

CONCLUSIONS

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.

摘要

背景

动物模型表明，γ-氨基丁酸能功能障碍在精神病的发生发展中起作用，且接触苯二氮䓬（BDZ）可预防与精神病相关的表型出现。然而，BDZ接触是否会影响人类患精神病的风险尚不清楚。

方法

这项观察性队列研究使用了818名临床高危精神病患者（CHR-P）的电子健康记录数据，以调查BDZ接触（包括催眠药，如佐匹克隆）是否能降低患精神病的风险和不良临床结局。在整个未匹配样本和倾向得分匹配（PSM）子样本中均采用了Cox比例风险模型。

结果

数据清理后纳入了567名CHR-P个体（105名接触BDZ，462名未接触BDZ）。306名（54%）个体为男性，平均年龄为22.3岁（标准差4.9）。接触BDZ组和未接触BDZ组在包括精神病症状严重程度在内的几个人口统计学和临床特征方面存在差异。在整个未匹配样本中，BDZ接触与转变为精神病的风险增加相关（风险比[HR]=1.61；95%置信区间[CI]：1.03 - 2.52；P=0.037）、精神病住院（HR=1.93；95%CI：1.13 - 3.29；P=0.017）、家访（HR=1.64；95%CI：1.18 - 2.28；P=0.004）以及急诊就诊（HR=1.88；95%CI：1.31 - 2.72；P<0.001）。然而，通过PSM控制指示性混杂因素后，BDZ接触并未调节任何结局的风险（所有P>0.05）。在仅限于未使用过抗精神病药物个体的分析中，BDZ接触在趋势水平上降低了转变为精神病的风险（HR=0.59；95%CI：0.32 - 1.08；P=0.089）。