Zolpidem引起之複雜性睡眠行為盛行率之統合分析

Abstract

背景：Zolpidem為目前全球使用量最大的安眠藥之一，雖因藥效快速、半衰期短且副作用相對較少而廣受臨床採用，但上市後一直有複雜性睡眠行為的相關案例，嚴重者甚至造成傷亡。藥廠仿單標示的發生率多為不常見（< 1%），然而現有文獻均僅止於文獻回顧，尚無統合分析研究整合各研究之盛行率數據。 目的：本研究旨在透過統合分析方法，估計成年zolpidem使用者的複雜性睡眠行為盛行率，並探討可能影響盛行率的相關因素，以提升臨床用藥安全。 方法：搜尋PubMed、Embase、Cochrane Library等多個中英文資料庫及預印本平台，搜尋截止時間為2026年3月。蒐集以夢遊或睡眠相關進食障礙為結果、且有數值可計算比值的臨床試驗及觀察性研究。統計分析採廣義線性混合模型，估計統合盛行率及95%信賴區間；並以敏感性分析以及次群體分析探討可能的異質性來源。 結果：共納入15篇研究，包含10篇zolpidem使用者研究（共4027人）及5篇身心科患者研究（共384651人）。Zolpidem使用者的複雜性睡眠行為盛行率為10.52%（95% CI：3.67–26.62%），顯著高於藥廠仿單的1%（p = 0.0008）。排除可能為離群值的單一研究後，盛行率提升至12.15%（95% CI：4.77–27.63%），且與身心科患者基線盛行率（3.85%）達到統計顯著差異（p = 0.037）。次群體分析顯示，排除離群研究後，有排除苯二氮平類藥物併用者的研究盛行率為3.58%（95% CI：1.97–6.41%），顯著低於未排除者的24.17%（95% CI：20.05–28.82%，p < 0.0001），顯示苯二氮平類藥物的併用可能是複雜性睡眠行為的相關因子。 結論：Zolpidem引起複雜性睡眠行為的盛行率可能高於仿單所標示的數字，而與苯二氮平類藥物的併用可能進一步提高發生風險。醫療人員面對多重用藥患者時，應積極評估並告知相關風險，以保障病患安全。

Background: Zolpidem, a non-benzodiazepine hypnotic (Z-drug), has become one of the most widely prescribed sedative-hypnotics worldwide due to its rapid onset, short half-life, and relatively favorable side-effect profile. However, cases of complex sleep behaviors (CSB), including sleepwalking and sleep-related eating disorders, have been reported since its introduction. Despite serious safety concerns—including injuries and deaths—the prevalence reported in manufacturer prescribing information remain below 1%, and no meta-analysis has yet synthesized available prevalence data. Objectives: This study aimed to estimate the prevalence of zolpidem-induced complex sleep behaviors in adult users through meta-analysis, and to identify factors potentially associated with their occurrence. Methods: Multiple databases—including PubMed, Embase, and Cochrane Library—as well as preprint servers were searched through March 2026. Eligible studies were clinical trials or observational studies reporting the number of sleepwalking or sleep-related eating disorder events in adult zolpidem users or psychiatric outpatients, with sufficient data for proportion calculation. A generalized linear mixed model (GLMM) was used to estimate pooled prevalence with 95% confidence intervals. Sensitivity analysis was conducted using leave-one-out approach and other indicators, also subgroup analyses were performed to explore sources of heterogeneity. Results: Fifteen studies were included: 10 involving zolpidem users (n = 4027) and 5 involving general psychiatric patients (n = 384651). The pooled CSB prevalence in zolpidem users was 10.52% (95% CI: 3.67–26.62%), significantly exceeding the 1% threshold stated in prescribing information (p = 0.0008). After excluding a potential outlier study, the prevalence increased to 14.81% (95% CI: 6.85–29.13%), which was significantly higher than the baseline prevalence in psychiatric patients (3.85%; p = 0.037). Subgroup analysis revealed that studies excluding concomitant use of other benzodiazepine hypnotics had a substantially lower prevalence of 3.58% (95% CI: 1.97–6.41%) compared to 24.17% (95% CI: 20.05–28.82%) in studies that did not exclude such co-use (p < 0.0001), suggesting concomitant benzodiazepine use may be a contributing factor to CSB occurrence. Conclusions: This meta-analysis indicates that the prevalence of zolpidem-induced complex sleep behaviors may be substantially higher than manufacturer-reported estimates, and that concomitant use of benzodiazepines may further increase the risk. Clinicians should proactively assess polypharmacy risks and counsel patients accordingly to enhance medication safety.