Department of Child & Adolescent Psychiatry and Institute of Psychiatry, Psychology & Neuroscience and Maudsley Biomedical Research Centre for Mental Health, King's College London, London, United Kingdom.
Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology & Neuroscience and Maudsley Biomedical Research Centre for Mental Health, King's College London, London, United Kingdom.
J Child Adolesc Psychopharmacol. 2022 May;32(4):233-241. doi: 10.1089/cap.2021.0137. Epub 2022 May 2.
Anxiety disorders are among the most common co-occurring conditions in autism spectrum disorder (ASD). Despite their prevalence and impact, there are no randomized controlled trials (RCTs) aimed at evaluating the efficacy of selective serotonin reuptake inhibitors (SSRIs) for anxiolysis in this population, who may have a different biological basis for anxiety. Secondary analyses of the STAART double-blind, placebo-controlled RCT of citalopram in children with ASD examined whether citalopram reduced anxiety measured on the parent-reported Child and Adolescent Symptom Inventory-4 (CASI-4) as the primary outcome. An intention-to-treat analysis involving all 149 participants used multiple imputations for missing data and included baseline stratification factors of age group and site, among others. We prespecified as clinically significant a 33% reduction in anxiety in citalopram versus placebo, coinciding with 80% power. We tested whether communicative ability on the Vineland Communication score moderated treatment effect and explored whether initial anxiety was associated with greater adverse events, which could impact on dose titration and achieving optimal dose. Both groups showed substantial reduction in anxiety. Citalopram was associated with a nonsignificant 16.5% greater reduction (observed coefficient = -0.181, bootstrap standard error = 0.126, = 0.151, confidence interval = -0.428 to 0.066). Anxiety reports were significantly lower in children with reduced communicative ability, but communicative ability did not moderate the treatment effect (interaction = 0.294). Initial anxiety levels were not associated with increased adverse effects (interaction s 0.162-0.954). Citalopram did not statistically significantly improve anxiety in children with ASD. Clinicians should be cautious in their use of SSRIs for this indication. There remains a need for well-powered clinical trials testing the efficacy of SSRIs among autistic children with anxiety disorders.
焦虑障碍是自闭症谱系障碍（ASD）中最常见的共病之一。尽管它们很普遍，而且对患者有影响，但目前还没有随机对照试验（RCT）旨在评估选择性 5-羟色胺再摄取抑制剂（SSRIs）对该人群焦虑症的疗效，因为他们的焦虑症可能有不同的生物学基础。对 STAART 双盲、安慰剂对照的西酞普兰治疗 ASD 儿童的 RCT 的二次分析检查了西酞普兰是否能降低作为主要结果的父母报告的儿童和青少年症状清单-4（CASI-4）上测量的焦虑。涉及所有 149 名参与者的意向治疗分析使用多重插补法处理缺失数据，并包括年龄组和地点等基线分层因素。我们预先指定了西酞普兰与安慰剂相比焦虑减少 33%作为临床显著标准，这与 80%的功效相对应。我们测试了 Vineland 沟通评分上的沟通能力是否调节了治疗效果，并探讨了初始焦虑是否与更多不良事件相关，这可能会影响剂量滴定和达到最佳剂量。两组患者的焦虑均有明显减轻。西酞普兰与非显著的 16.5%更大的缓解相关（观察系数 = -0.181，引导标准误差 = 0.126， = 0.151，置信区间 = -0.428 至 0.066）。沟通能力降低的儿童焦虑报告明显较低，但沟通能力并未调节治疗效果（交互作用 = 0.294）。初始焦虑水平与不良反应增加无关（交互作用 s 0.162-0.954）。西酞普兰并未显著改善 ASD 儿童的焦虑。临床医生在为该适应症使用 SSRIs 时应谨慎。仍需要进行功效更强的临床试验，以测试 SSRIs 在患有焦虑症的自闭症儿童中的疗效。
