Holland Bloorview Kids Rehabilitation Hospital.
Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
Curr Opin Neurol. 2018 Apr;31(2):119-125. doi: 10.1097/WCO.0000000000000542.
The purpose of this manuscript is to review the evidence generated by clinical trials of pharmaceuticals in autism spectrum disorder (ASD), describe challenges in the conduct of such trials, and discuss future directions RECENT FINDINGS: Clinical trials in ASD have produced several compounds to adequately support the pharmacological treatment of associated symptom domains: attention deficit hyperactivity disorder (methylphenidate, atomoxetine, and alpha agonists), irritability/aggression (risperidone and aripiprazole), sleep (melatonin), and weight gain associated with atypical antipsychotic use (metformin). However, there is no evidence yet to support the routine use of pharmaceuticals for the treatment of core symptom domains. Challenges in the field include biological heterogeneity within ASD, lack of biomarkers that clarify biological heterogeneity or predict response to treatment, lack of data across the lifespan, and suboptimal outcome measures.
Several compounds have evidence for the treatment of co-occurring symptoms in children and youth with ASD, although pharmacological interventions for core symptoms are still lacking. Identifying the various biologies underling ASD and developing biomarkers that stratify biologically homogeneous populations are both necessary to realize the promise of precision medicine in ASD.
本文旨在综述自闭症谱系障碍（ASD）药物临床试验所产生的证据，描述此类试验开展过程中的挑战，并讨论未来方向。
ASD 的临床试验产生了几种化合物，足以充分支持相关症状领域的药物治疗：注意缺陷多动障碍（哌甲酯、托莫西汀和α 受体激动剂）、易激惹/攻击行为（利培酮和阿立哌唑）、睡眠（褪黑素）以及与非典型抗精神病药物使用相关的体重增加（二甲双胍）。然而，目前尚无证据支持将药物常规用于治疗核心症状领域。该领域的挑战包括 ASD 内的生物学异质性、缺乏阐明生物学异质性或预测治疗反应的生物标志物、缺乏整个生命周期的数据以及不适当的结果测量。
尽管针对核心症状的药物干预仍有待进一步研究，但已有几种化合物被证明可用于治疗 ASD 儿童和青少年的共患病症状。为了实现 ASD 精准医学的承诺，有必要确定 ASD 背后的各种生物学机制，并开发能够对生物学同质人群进行分层的生物标志物。
