Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges’ g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges’ g − 0.857, 95% CI − 1.263 to − 0.451, certainty of evidence: high) and aripiprazole (Hedges’ g − 0.559, 95% CI − 0.767 to − 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges’ g − 0.893, 95% CI − 1.184 to − 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.

中文翻译：

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针对自闭症谱系障碍易激惹的药物和非药物干预措施：使用 GRADE 评估进行系统评价和荟萃分析

人们已经对多种针对自闭症谱系障碍 (ASD) 烦躁的干预措施进行了研究。我们的目的是评估药物和非药物干预措施对自闭症谱系障碍（ASD）易激惹的影响程度，且对合格干预措施没有任何限制。我们系统地检索了 PubMed/MEDLINE、Scopus 和 Web of Science，直至 2023 年 4 月 15 日。我们纳入了采用平行设计的随机对照试验 (RCT)，该试验检查了干预措施治疗任何年龄的 ASD 患者易激惹的效果，而无需进行任何干预。对合格干预措施的任何限制。我们通过将效应大小合并为 Hedges g 来进行随机效应荟萃分析。我们将评估的干预措施分类如下：药物单一疗法、利培酮加辅助治疗与利培酮单一疗法、非药物干预和饮食干预。我们利用 Cochrane 工具评估每项研究的偏倚风险，并利用 GRADE 方法评估每项荟萃分析干预措施证据的确定性。在 5640 篇参考文献中，我们确定了 60 篇符合条件的文章，涉及 45 种不同的干预措施，包括 3531 名参与者，其中 80.9% 是男性（平均年龄 [SD] = 8.79 [3.85]）。对于药物单一疗法，利培酮（Hedges' g − 0.857，95% CI − 1.263 至 − 0.451，证据质量：高）和阿立哌唑（Hedges' g − 0.559，95% CI − 0.767 至 − 0.351，证据质量：高） ）优于安慰剂。在非药物干预措施中，家长培训（Hedges g − 0.893，95% CI − 1.184 至 − 0.602，证据质量：中等）显示出显着效果。荟萃分析的干预措施在利培酮+辅助治疗和膳食补充剂中均未产生显着效果。然而，几种新分子增强利培酮的效果优于利培酮单一疗法，但均来自一项随机对照试验。首先，已经使用各种工具来测量自闭症谱系障碍的烦躁性，这可能导致结果的异质性。其次，每种干预措施的荟萃分析仅包括少量研究和参与者。对于自闭症谱系障碍 (ASD) 的烦躁症状，药物干预措施中仅推荐利培酮、阿立哌唑，非药物干预措施中仅推荐家长培训。作为利培酮的增强剂，几种新疗法显示出有希望的效果，但需要进一步的随机对照试验来复制研究结果。试用注册PROSPERO，CRD42021243965。