Treatment of Autism Spectrum Disorders with a Glutamate Antagonist

目前，还没有一种药物可以有效治疗自闭症的核心症状——社交缺陷、沟通异常和固定兴趣/重复行为。鉴于自闭症谱系障碍（ASD）的重复行为与强迫症（OCD）中的强迫仪式在临床上的相似性，以及ASD和OCD的常见合并症，我们有理由假设对OCD有效的治疗药物也将对ASD和OCD个体有效。认知行为疗法和5 -羟色胺再摄取阻断药物（SSRIs，如氟西汀、氟伏沙明和舍曲林）已被证明对治疗强迫症有效，但许多患者对治疗无效。治疗难治性病例在ASD-OCD共病组中尤为常见。

Currently, there is no medication that is effective in treating the core symptoms of autism -- social deficits, communication abnormalities and fixated interests/repetitive behaviors. Given the clinical similarity between the repetitive behaviors of autism spectrum disorder (ASD) and the compulsive rituals seen in obsessive-compulsive disorder (OCD), and the frequent comorbidity of ASD and OCD, it is reasonable to hypothesize that medications which are effective in the treatment of OCD also will be effective in the treatment of individuals with ASD and OCD. Cognitive-behavioral therapy and serotonin reuptake blocking medications (SSRIs, such as fluoxetine, fluvoxamine and sertraline) have been demonstrated to be efficacious in the treatment of OCD, but many patients fail to respond to therapy. Treatment-refractory cases are particularly common among the comorbid ASD-OCD group. The hypothesized etiology of OCD suggests that glutamate antagonists, such as riluzole, might be beneficial as they impact the system "upstream" from current pharmacotherapies. There has been some preliminary success in the use of riluzole for OCD. For example, an open label trial of riluzole augmentation was conducted in 13 adult patients with treatment-resistant OCD. Concomitant medicines were continued during the trial and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores improved significantly over the course of the investigation. Five subjects were categorized as treatment responders (Y-BOCS less than 16, and 35% or greater reduction in baseline score as well as clinical consensus improvement). An open-label 12 weeks trial of riluzole in pediatric patients with OCD resulted in significant improvements for 4 of the 6 participants; the treatment gains were sustained at one year follow-up. These pilot data provide support for the current trial. The study is a 12-week, placebo-controlled investigation of the safety and efficacy of riluzole for the treatment of obsessive-compulsive symptoms among 30 children and adolescents(ages 7 to 17 years), with autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD). Subjects will receive masked capsules containing riluzole or placebo during the 12 weeks long controlled phase of the trial and will be invited then to continue/take open-label riluzole for three months. Periodic clinic visits continue through next six months with the final evaluation occurring one year after randomization. The study is actively recruiting subjects aged 7 - 17 years. Children and adolescents are eligible for study inclusion if they have moderate-severe obsessions and/or compulsions (repetitive behaviors) and a pervasive developmental disorder (Autism, PDD-NOS or Asperger disorder).