Comparative efficacy and tolerability of antidopaminergic and muscarinic antipsychotics for acute schizophrenia: a network meta-analysis of randomised controlled trials indexed in international English and Chinese databases.

In 2024, a new-in-class muscarinic receptor agonist (xanomeline-trospium) was licenced, acting upstream of antidopaminergic agents, and providing hope to decrease the adverse effects burden of antipsychotics.

2024年，一种新型的毒蕈碱受体激动剂（xanomeline-trospium）获得批准，其作用于抗多巴胺药物上游，有望减轻抗精神病药物的不良反应负担。

We aimed to compare the efficacy and tolerability of antipsychotics by performing network meta-analysisof randomised controlled trials (RCTs).

我们的目标是通过执行随机对照试验（RCTs）的网络荟萃分析，比较抗精神病药物的疗效和耐受性。

Methods

This systematic review(PROSPERO, CRD42022380708) included blinded and open RCTs investigating antipsychotic drugs in participants of any age with acute psychotic symptoms of schizophrenia over 3 weeks to 3 months.

这项系统评价（PROSPERO, CRD42022380708）包括了对任何年龄的参与者进行的盲法和开放标签的随机对照试验，这些试验研究了在3周至3个月期间患有精神分裂症急性精神病症状的抗精神病药物。

Included antipsychotics comprised 23 primarily dopamine-receptor blocking medications and the muscarinic receptor agonist xanomeline-trospium in different applications.

纳入的抗精神病药物包括23种主要的多巴胺受体拮抗剂和胆碱能受体激动剂xanomeline-trospium，它们在不同的应用中使用。

We searched Cochrane Schizophrenia group's register, previous reviews, and five Chinese databases for trials published from database inception until July 26, 2024 and contacted authors to assess trials' methodological quality; only trials with appropriate randomisation indicated were included.

我们搜索了Cochrane精神分裂症小组的注册库、以往的综述以及五个中文数据库，以获取从数据库开始到2024年7月26日发表的试验，并联系了作者以评估试验的方法学质量；只有那些表明有适当随机化的试验才被纳入。

The primary outcome was rating scale-measured overall symptoms of schizophrenia (efficacy) analysed with random-effects frequentist network meta-analysis.

主要结果是使用随机效应频率网络荟萃分析评估的精神分裂症总体症状（疗效）的评分量表测量结果。

Secondary outcomes comprised 32 further efficacy and tolerability outcomes.

次要结果包括32项进一步的疗效和耐受性结果。

The confidence in the estimates was assessed using the Confidence in Network Meta-Analysisapproach.

使用网络荟萃分析方法评估了估计的可信度。

Results

After screening 18 859 references and contacting authors of 5428 trials, we included 438 RCTs.

在筛选了18,859篇参考文献并联系了5428项试验的作者后，我们纳入了438项随机对照试验。

Of those, 388 RCTs with 78 193 participants (28 448 women and 49 745 men) provided usable data for at least one outcome. 5117 Chinese trials were identified but most were excluded because authors did not reply or reported serious methodological concerns. 256 double-blindstudies with 58 948 participants provided usable data for the primary outcome.

在这些研究中，388项随机对照试验（RCTs）涉及78,193名参与者（28,448名女性和49,745名男性），至少为一个结果提供了可用数据。共识别出5,117项中国试验，但大多数因作者未回复或报告了严重的的方法学问题而被排除。256项双盲研究涉及58,948名参与者，为主要结果提供了可用数据。

All antipsychotics reduced symptoms more than placebo with standardised mean differences ranging from -0·90 (95% CI -1·03 to -0·77) to -0·23 (-0·39 to -0·06).

所有抗精神病药物均比安慰剂更能减轻症状，标准化平均差异范围从-0·90（95% 置信区间 -1·03至-0·77）到-0·23（-0·39至-0·06）。

Particularly clozapine, as well as amisulpride, olanzapine, and risperidone were more efficacious than at least three other antipsychotics (confidence in estimates were low-to-moderate).

特别是氯氮平，以及阿立哌唑、奥氮平和利培酮，比至少三种其他抗精神病药物更有效（估计的信心水平为低至中等）。

Adverse effects varied across medications.

药物的不良反应在不同药物间存在差异。

interpretation

This network meta-analysisprovides evidence for small-to-medium clinically relevant differences between antipsychotics in efficacy; this finding warrants stronger and more specific emphasis in clinical guidelines.

这项网络荟萃分析提供了抗精神病药物在疗效上小到中等程度的临床相关差异的证据；这一发现需要在临床指南中得到更强和更具体的强调。

Nonetheless, important differences in tolerability need to be considered for individualised drug choice, with partial dopamine agonists having overall better tolerability and xanomeline-trospium lacking adverse effects of dopamine-blocking agents but resulting in cholinergic and anticholinergic adverse events.

然而，为了个体化药物选择，需要考虑耐受性的重大差异，部分多巴胺激动剂总体上具有更好的耐受性，而xanomeline-trospium缺乏多巴胺阻断剂的不良反应，但会引起胆碱能和抗胆碱能不良事件。

Future research should directly compare xanomeline-trospium with other antipsychotics to confirm its efficacy; modern trials using clozapine early in schizophrenia are needed to establish whether it improves outcomes and prevents chronification.

未来的研究应直接比较xanomeline-trospium与其他抗精神病药物，以确认其疗效；需要进行现代试验，早期使用氯氮平治疗精神分裂症，以确定是否能改善结果并预防慢性化。

funding

German Research Foundation, German Ministry of Research, Technology and Space, and National Natural Science Foundation of China.

德国研究基金会、德国研究、技术和空间部以及中国国家自然科学基金。