氯丙咪林治疗精神分裂症的疗效、耐受性和安全性：一项系统综述和荟萃分析。

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology Pub Date : 2024-12-25 DOI:10.1016/j.euroneuro.2024.11.013

Nicholas Fabiano , Stanley Wong , Carl Zhou , Christoph U. Correll , Mikkel Højlund , Marco Solmi

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引用次数: 0

摘要

美国食品和药物管理局于2024年9月26日批准了xanomelin -trospium联合治疗精神分裂症。我们对xanomeline-trospium在精神分裂症患者随机对照试验中的有效性和安全性进行了一项符合PRISMA 2020标准的系统评价和随机效应荟萃分析（MEDLINE， EMBASE, Cochrane, PsycINFO, October-01-2024）。共同主要结局为阳性和阴性综合征量表（PANSS）总分（标准化平均差=SMD）和全因停药（风险比=RR）。采用Cochrane’s Risk of Bias （RoB）工具2和GRADE。Xanomeline-trospium （k = 3，精神分裂症急性加重，RoB=低，基线N = 690，男性= 75.5%，年龄=44.3 + 11.0，持续时间=5周）在PANSS总分（SMD=-0.56, 95%可信区间/CI=-0.72/-0.40）、阳性（SMD=-0.59, 95% CI=-0.75/-0.43）、阴性（SMD=-0.33, 95% CI=-0.49/-0.17）和Marder Factor阴性症状评分（SMD=-0.36, 95% CI=-0.60/-0.13）、临床总体印象-严重程度（SMD=-0.54, 95% CI=-0.71/-0.37）（GRADE=中度）上优于安慰剂。和反应（较基线降低≥30%:RR=2.13, 95% CI=1.66-2.75）。体重增加≥7% （RR=0.46, 95% CI=0.25-0.87， NNT=19）、低密度脂蛋白-胆固醇和高密度脂蛋白-胆固醇水平的风险降低，而呕吐、高血压、恶心、口干、消化不良、便秘（RR=7.60, 95% CI=1.50-38.57至RR=2.72, 95% CI=1.63-4.55）、任何不良事件（RR=1.33, 95% CI=1.18-1.51， NNT=6）、甘油三酯水平和仰卧心率（GRADE=中高）的风险增加。相反，任何其他严重或严重不良事件或全因停药的风险均未增加。在事后分析中，从第2周开始，xanomeline-trospium在缓解（≥20%和≥30%阈值）、有明显阴性症状的患者出现阴性症状以及低于一般人群标准≥1个标准差的患者出现认知症状方面优于安慰剂。此外，亲/抗胆碱能的副作用是轻度至中度的，而且大多是短暂的。Xanomeline-trospium是一种治疗精神分裂症的有效药物，具有独特的耐受性，可能解决未满足的需求。

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Efficacy, tolerability, and safety of xanomeline-trospium chloride for schizophrenia: A systematic review and meta-analysis

The United States Food and Drug Administration approved xanomeline-trospium combination for schizophrenia on September-26–2024. We conducted a PRISMA 2020-compliant systematic review with random-effects meta-analysis on the efficacy and safety of xanomeline-trospium in randomized controlled trials in patients with schizophrenia (MEDLINE, EMBASE, Cochrane, PsycINFO, October-01–2024). Co-primary outcomes were Positive And Negative Syndrome Scale (PANSS) total score (standardized mean difference=SMD), and all-cause discontinuation (risk ratio=RR). Cochrane's Risk of Bias (RoB) Tool 2 and GRADE were used. Xanomeline-trospium (k = 3, schizophrenia acute exacerbation, RoB=low, baseline N = 690, males=75.5 %, age=44.3 + 11.0, duration=5 weeks) outperformed placebo on PANSS total (SMD=-0.56, 95 % confidence interval/CI=-0.72/-0.40), positive (SMD=-0.59, 95 %CI=-0.75/-0.43), negative (SMD=-0.33, 95 %CI=-0.49/-0.17), and Marder Factor negative symptom score (SMD=-0.36, 95 %CI=-0.60/-0.13), Clinical Global Impression-Severity (SMD=-0.54, 95 %CI=-0.71/-0.37) (GRADE=moderate), and response (≥30 % reduction from baseline: RR=2.13, 95 %CI=1.66–2.75). Risk of ≥7 % weight gain (RR=0.46, 95 %CI=0.25–0.87, NNT=19), low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol levels were reduced, while risk was increased for vomiting, hypertension, nausea, dry mouth, dyspepsia, constipation (RR=7.60, 95 %CI=1.50–38.57 to RR=2.72, 95 %CI=1.63–4.55), any adverse event (RR=1.33, 95 %CI=1.18–1.51, NNT=6), triglyceride levels and supine heart rate (GRADE=moderate to high). Conversely, the risk was not increased for any other, serious, or severe adverse events or all-cause discontinuation. In post-hoc analyses, xanomeline-trospium outperformed placebo regarding response (≥20 % and ≥30 % threshold) starting at week 2, negative symptoms in patients with prominent negative symptoms, and cognitive symptoms in patients ≥1 standard deviation below the general population norm. Further, pro-/anti-cholinergic side effects were mild-moderate and mostly transient. Xanomeline-trospium is an effective treatment for schizophrenia with a unique tolerability profile, potentially addressing unmet needs.

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来源期刊

European Neuropsychopharmacology 医学-精神病学

CiteScore

10.30

自引率

5.40%

发文量

730

审稿时长

41 days

期刊介绍： European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.