Salazar de Pablo Gonzalo, Pastor Jordá Carolina, Vaquerizo-Serrano Julio, Moreno Carmen, Cabras Anna, Arango Celso, Hernández Patricia, Veenstra-VanderWeele Jeremy, Simonoff Emily, Fusar-Poli Paolo, Santosh Paramala, Cortese Samuele, Parellada Mara
Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, United Kingdom; Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, United Kingdom.
University of Pittsburgh Medical Center, Pittsburgh, the Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, and Hospital Universitario 12 de Octubre, Madrid, Spain.
J Am Acad Child Adolesc Psychiatry. 2023 Feb;62(2):151-168. doi: 10.1016/j.jaac.2022.03.033. Epub 2022 Apr 22.
Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a broad range of pharmacological interventions for emotional dysregulation and irritability in ASD and predictors of response.
Following a preregistered protocol (PROSPERO: CRD42021235779), we systematically searched multiple databases until January 1, 2021. We included placebo-controlled randomized controlled trials (RCTs) and evaluated the efficacy of pharmacological interventions and predictors of response for emotional dysregulation and irritability. We assessed heterogeneity using Q statistics and publication bias. We conducted subanalyses and meta-regressions to identify predictors of response. The primary effect size was the standardized mean difference. Quality of studies was assessed using the Cochrane Risk of Bias Tool (RoB2).
A total of 2,856 individuals with ASD in 45 studies were included, among which 26.7% of RCTs had a high risk of bias. Compared to placebo, antipsychotics (standardized mean difference = 1.028, 95% CI = 0.824-1.232) and medications used to treat attention-deficit/hyperactivity disorder (ADHD) (0.471, 0.061-0.881) were significantly better than placebo in improving emotional dysregulation and irritability, whereas evidence of efficacy was not found for other drug classes (p > .05). Within individual medications, evidence of efficacy was found for aripiprazole (1.179, 0.838-1.520) and risperidone (1.074, 0.818-1.331). Increased rates of comorbid epilepsy (β = -0.049, p = .026) were associated with a lower efficacy.
Some pharmacological interventions (particularly risperidone and aripiprazole) have proved efficacy for short-term treatment of emotional dysregulation and irritability in ASD and should be considered within a multimodal treatment plan, taking into account also the tolerability profile and families' preferences.
情绪调节障碍和易怒在自闭症谱系障碍（ASD）患者中很常见。我们进行了首次荟萃分析，评估了一系列药物干预对ASD患者情绪调节障碍和易怒的疗效及反应预测因素。
按照预先注册的方案（PROSPERO：CRD42021235779），我们系统检索了多个数据库直至2021年1月1日。我们纳入了安慰剂对照的随机对照试验（RCT），并评估了药物干预对情绪调节障碍和易怒的疗效及反应预测因素。我们使用Q统计量和发表偏倚评估异质性。我们进行了亚组分析和荟萃回归以确定反应预测因素。主要效应量为标准化均值差。使用Cochrane偏倚风险工具（RoB2）评估研究质量。
共纳入45项研究中的2856名ASD患者，其中26.7%的RCT存在高偏倚风险。与安慰剂相比，抗精神病药物（标准化均值差 = 1.028，95%置信区间 = 0.824 - 1.232）和用于治疗注意力缺陷多动障碍（ADHD）的药物（0.471，0.061 - 0.881）在改善情绪调节障碍和易怒方面显著优于安慰剂，而其他药物类别未发现疗效证据（p > 0.05）。在个别药物中，阿立哌唑（1.179，0.838 - 1.520）和利培酮（1.074，0.818 - 1.331）有疗效证据。共患癫痫的发生率增加（β = -0.049，p = 0.026）与疗效较低相关。
一些药物干预（特别是利培酮和阿立哌唑）已被证明对ASD患者情绪调节障碍和易怒的短期治疗有效，应在多模式治疗计划中予以考虑，同时也要考虑耐受性和家庭偏好。
