Abstract

The US FDA issued a black-box warning against co-prescription of antipsychotic (AP) agents and opioids due to the risk of respiratory depression, but evidence on the comparative safety of sedating vs nonsedating APs is lacking. We classified APs as sedating (eg, quetiapine, olanzapine, and chlorpromazine) and nonsedating (eg, aripiprazole, haloperidol, and risperidone) based on their affinity to the histamine-1 neuroreceptor (K_i < or ≥20, respectively) and sought to compare the rate of overdose between patients using sedating vs nonsedating APs plus opioids. We constructed a population-based cohort nested in the IBM MarketScan database (2004–2017). Patients with concomitant use of sedating APs and prescription opioids (“exposed”) were 1:1 matched to patients with concomitant use of nonsedating APs and prescription opioids (“referent”) based on the propensity score (PS). The primary outcome was any hospitalization or emergency department visit due to an overdose within 30 days. The final cohort comprised 62 604 exposed and an equal number of PS-matched reference patients. Characteristics of matched exposed and reference patients were similar. There were 178 overdose events among the exposed (35.3 events per 1000 person-years [PY]) vs 133 among the reference group (26.4 events per 1000 PY), for an adjusted hazard ratio of 1.34 (95% CI: 1.07-1.68). This finding was consistent across sensitivity and subgroup analyses. Among patients receiving prescription opioids, concomitant use of sedating APs was associated with an increased risk of overdose compared with nonsedating APs. Caution is required when co-prescribing opioids and APs. If co-prescription is needed, choosing a nonsedating agent should be preferred whenever possible given the clinical context.

中文翻译：

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与抗精神病药和阿片类药物共同处方相关的过量风险：一项基于人群的队列研究

摘要

由于存在呼吸抑制的风险，美国 FDA 发布了针对抗精神病 (AP) 剂和阿片类药物联合处方的黑框警告，但缺乏镇静剂与非镇静剂 AP 的比较安全性的证据。我们根据 AP 对组胺 1 神经受体的亲和力（K _i<或≥20，分别）并试图比较使用镇静剂与非镇静剂加阿片类药物的患者之间的过量率。我们构建了一个嵌套在 IBM MarketScan 数据库 (2004-2017) 中的基于人群的队列。根据倾向评分 (PS)，同时使用镇静 AP 和处方阿片类药物（“暴露”）的患者与同时使用非镇静 AP 和处方阿片类药物（“参照”）的患者 1:1 匹配。主要结果是在 30 天内因服药过量而住院或急诊就诊。最终队列包括 62 604 名暴露患者和同等数量的 PS 匹配参考患者。匹配的暴露患者和参考患者的特征相似。暴露组中有 178 起过量事件（每 1000 人年 [PY] 35.3 起事件），而参考组中有 133 起（26. 每 1000 年 4 次事件），调整后的风险比为 1.34（95% CI：1.07-1.68）。这一发现在敏感性和亚组分析中是一致的。在接受处方阿片类药物的患者中，与非镇静 AP 相比，同时使用镇静 AP 与过量风险增加相关。共同处方阿片类药物和 AP 时需要谨慎。如果需要共同处方，考虑到临床情况，应尽可能选择非镇静剂。