lumateperone治疗双相抑郁症的剂量反应疗效和安全性:随机对照试验的初步荟萃分析。

IF 5.5 3区 医学 Q1 CLINICAL NEUROLOGY
Chih-Wei Hsu, Yu-Kang Tu, Kuo-Chuan Hung, Chih-Sung Liang, Ping-Tao Tseng, Yang-Chieh Brian Chen
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引用次数: 0

摘要

背景:治疗双相抑郁症的最佳剂量仍不确定。目的:探讨其疗效和安全性的量效关系。方法:系统检索各大数据库至2025年7月1日。疗效结果包括抑郁严重程度、整体疾病严重程度、生活质量、应答者和缓解者率的变化。安全性结局包括全因退出、因不良事件(AE)而停药、治疗中出现的AE、躁狂、自杀、锥体外系症状、体重、血脂和空腹血糖。一步剂量-反应荟萃分析产生效应大小,报告为标准化平均差异(smd)和95%置信区间(ci)的风险比(rr)。结果:涉及1454例患者的3项随机对照试验显示,每日42毫克剂量的lumateperone可显著改善抑郁症状(SMD = -0.26, 95% CI: -0.51, -0.02)、临床总体印象-双相情感严重程度(CI - bp - s)整体双相情感疾病(SMD = -0.31, 95% CI: -0.45, -0.16)、CI - bp - s双相情感抑郁(SMD = -0.33, 95% CI: -0.48, -0.17)、生活质量(SMD = 0.22, 95% CI: 0.07, 0.36)和应答率(RR = 1.27;95% CI: 1.05, 1.53),但不包括发送者率(1.06;95% CI: 0.81, 1.38)。与安慰剂相比,42 mg剂量组因AE引起的停药显著增加(RR = 3.12; 95% CI: 1.68, 5.80),但28 mg剂量组无此差异(1.58;95% CI: 0.25, 9.89)。此外,退药率(42 mg RR = 1.15; 95% CI: 0.76, 1.73)和其他安全性结局没有表现出剂量-反应趋势。结论:初步证据表明,每天服用42毫克lumateperone可能对双相抑郁症有临床益处,但ae相关的高停药率在实践中值得谨慎。然而,目前的数据仍然有限,需要进一步的研究来确定平衡疗效和安全性的最佳剂量范围。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dose-response efficacy and safety of lumateperone in bipolar depression: A preliminary meta-analysis of randomized controlled trials.

Background: The optimal lumateperone dose for bipolar depression remains uncertain.

Aims: To examine its dose-response relationship for efficacy and safety.

Methods: We systematically searched major databases to 1 July 2025. Efficacy outcomes included change in depression severity, global illness severity, quality of life, responder, and remitter rates. Safety outcomes included all-cause dropout, discontinuations due to adverse event (AE), treatment-emergent AE, mania, suicidality, extrapyramidal symptoms, body weight, lipid profile, and fasting glucose. A one-step dose-response meta-analysis generated effect sizes, reported as standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs).

Results: Three randomized controlled trials involving 1454 patients showed that a 42-mg daily dose of lumateperone significantly improved depressive symptoms (SMD = -0.26; 95% CI: -0.51, -0.02), Clinical Global Impression-Bipolar-Severity (CGI-BP-S) overall bipolar illness (SMD = -0.31; 95% CI: -0.45, -0.16), CGI-BP-S bipolar depression (SMD = -0.33; 95% CI: -0.48, -0.17), quality of life (SMD = 0.22; 95% CI: 0.07, 0.36), and responder rate (RR = 1.27; 95% CI: 1.05, 1.53), but not remitter rate (1.06; 95% CI: 0.81, 1.38). Compared with placebo, discontinuation due to AE significantly increased at the 42 mg dose (RR = 3.12; 95% CI: 1.68, 5.80), but not at 28 mg (1.58; 95% CI: 0.25, 9.89). Moreover, dropout rates (42 mg RR = 1.15; 95% CI: 0.76, 1.73) and other safety outcomes did not exhibit a dose-response trend.

Conclusions: Preliminary evidence suggests that 42 mg daily of lumateperone may provide clinical benefit in bipolar depression, yet the higher rate of AE-related discontinuation warrants caution in practice. However, current data remain limited, requiring further studies to establish the optimal dosing range balancing efficacy and safety.

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来源期刊
Journal of Psychopharmacology
Journal of Psychopharmacology 医学-精神病学
CiteScore
8.60
自引率
4.90%
发文量
126
审稿时长
3-8 weeks
期刊介绍: The Journal of Psychopharmacology is a fully peer-reviewed, international journal that publishes original research and review articles on preclinical and clinical aspects of psychopharmacology. The journal provides an essential forum for researchers and practicing clinicians on the effects of drugs on animal and human behavior, and the mechanisms underlying these effects. The Journal of Psychopharmacology is truly international in scope and readership.
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