目的:睡眠问题和失眠很常见,具有挑战性的治疗,超越特定的诊断。虽然曲唑酮是一个受欢迎的选择,缺乏可靠的元分析证据。本系统评价和荟萃分析研究曲唑酮治疗睡眠障碍的有效性和安全性。反映失眠诊断和治疗的最新进展。
方法:我们搜索了Medline,Embase,APAPsycINFO,Cochrane中央控制试验登记册(CENTRAL),ClinicalTrials.gov,以及截至2024年5月1日的世界卫生组织(WHO)国际临床试验注册平台(ICTRP),用于比较曲唑酮与安慰剂并报告睡眠相关结局的随机对照试验(RCT).最短药物治疗时间为5天。包括所有RCT,无论致盲(开放标签或单盲或双盲),而准随机研究被排除.随机试验的Cochrane偏倚风险工具评估偏倚。分析在意向治疗(ITT)基础上使用随机效应模型。风险比(RR)用于二分结果,加权平均差(WMD)用于连续结果。当使用不同的单位或刻度时,计算Hedge调整后的g标准化平均差(SMD)。亚组和预先计划的敏感性分析探讨了异质性,并评估了研究结果的强度和一致性。
结果:总计,纳入44项RCT,3935名参与者。曲唑酮对主观总睡眠时间(TST)没有显着影响[WMD=0.73分钟,95%置信区间(CI)-24.62;26.07,p=0.96],但改善了睡眠质量(SQ)(SMD=-0.58,95%CI-0.87;-0.28,p<0.01)和次要结局。这些包括夜间觉醒的次数(SMD=-0.57,95%CI-0.85;-0.30],p<0.01),睡眠开始后的夜间清醒时间(WMD=-13.47分钟,95%CI-23.09;-3.86],p<0.01),通过多导睡眠图(WMD=27.98分钟,95%CI4.02;51.95,p=0.02),和睡眠效率(WMD=3.32,95%CI0.53;1.57,p=0.02)。耐受性问题包括由于不良反应导致更多的辍学(RR=2.30,95%CI1.45;3.64,p<0.01),任何与睡眠相关的不良反应(RR=3.67,95%CI1.07;12.47,p=0.04),一般不良反应较多(RR=1.18,95%CI1.03;1.33,p=0.02),睡眠相关不良反应较多(RR=4.31,95%CI2.29;8.13,p<0.01)。
结论:曲唑酮延长了总睡眠时间,但不影响感知的睡眠时间。它可以改善睡眠质量和连续性,但对睡眠潜伏期影响较小,效率,和白天的障碍。曲唑酮与不良反应有关,需要进行仔细的风险收益评估。有限的数据限制了普适性,强调需要更多的研究。
背景:PROSPERO注册号,CRD42022333121。
OBJECTIVE: Sleep problems and insomnia are common, challenging to treat, and transcend specific diagnoses. Although
trazodone is a popular choice, robust meta-analytic evidence is lacking. This systematic review and meta-analysis investigates the efficacy and safety of
trazodone for sleep disturbances, reflecting recent updates in insomnia diagnosis and treatment.
METHODS: We searched Medline, Embase, APA PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 1 May 2024, for Randomized Controlled Trials (RCTs) comparing trazodone with placebo and reporting sleep-related outcomes. The minimum pharmacotherapy duration was 5 days. Included were all RCTs regardless of blinding (open-label or single- or double-blind), while quasi-randomized studies were excluded. The Cochrane Risk of Bias Tool for Randomized Trials assessed bias. Analyses used a random-effects model on an intention-to-treat (ITT) basis. Risk ratio (RR) was used for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes. When different units or scales were used, Hedge\'s adjusted g standardized mean difference (SMD) was calculated. Subgroup and preplanned sensitivity analyses explored heterogeneity and evaluated findings\' strength and consistency.
RESULTS: In total, 44 RCTs with 3935 participants were included.
Trazodone did not significantly impact subjective total sleep time (TST) [WMD = 0.73 min, 95% confidence interval (CI) - 24.62; 26.07, p = 0.96] but improved sleep quality (SQ) (SMD = - 0.58, 95% CI - 0.87; - 0.28, p < 0.01) and secondary outcomes. These included the number of nocturnal awakenings (SMD = - 0.57, 95% CI - 0.85; - 0.30], p < 0.01), nocturnal time awake after sleep onset (WMD = - 13.47 min, 95% CI - 23.09; - 3.86], p < 0.01), objective TST by polysomnography (WMD = 27.98 min, 95% CI 4.02; 51.95, p = 0.02), and sleep efficiency (WMD = 3.32, 95% CI 0.53; 1.57, p = 0.02). Tolerability issues included more dropouts owing to adverse effects (RR = 2.30, 95% CI 1.45; 3.64, p < 0.01), any sleep-related adverse effects (RR = 3.67, 95% CI 1.07; 12.47, p = 0.04), more adverse effects in general (RR = 1.18, 95% CI 1.03; 1.33, p = 0.02), and more sleep-related adverse effects (RR = 4.31, 95% CI 2.29; 8.13, p < 0.01).
CONCLUSIONS: Trazodone extends total sleep time but does not affect perceived sleep duration. It may improve sleep quality and continuity but has minor effects on sleep latency, efficiency, and daytime impairment.
Trazodone is associated with adverse effects, necessitating a careful risk-benefit assessment. Limited data restrict generalizability, underscoring the need for more research.
BACKGROUND: PROSPERO registration number,CRD42022383121.