Trial of a Glutamate Antagonist in the Treatment of OCD and Autistic Disorders

血清素再摄取阻断药物（SSRIs，如氟西汀、氟伏沙明和舍曲林）已被证明对治疗强迫症（OCD）有效，但许多患者对治疗无效。治疗难治性病例在ASD-OCD合并症组中尤为常见，这表明仅调节血清素不足以缓解该队列的症状。儿童期发病强迫症的假设病因表明，谷氨酸拮抗剂，如利鲁唑，可能会降低强迫和强迫的严重程度，因为这种药物在当前药物治疗的“上游”起作用。在成人和儿童中使用利鲁唑治疗强迫症已经取得了一些初步的成功。一项开放标签试验利鲁唑增强在13名成人治疗难治性强迫症患者中进行。在试验期间继续服用伴随药物，耶鲁-布朗强迫症量表（Y-BOCS）得分在调查过程中显著提高。5名受试者被归类为治疗应答者（Y-BOCS小于16，基线评分降低35%或更高，临床共识改善）。6名患有强迫症的儿童受试者中有4名在服用利鲁唑12周后表现出显著改善；治疗效果持续一年随访，无严重不良事件报告。强迫行为，包括简单的、重复的行为，和更复杂的仪式一样得到改善，这表明利鲁唑可能对自闭症的刻板行为，以及强迫症和强迫行为有好处。

The serotonin reuptake blocking medications (SSRIs, such as fluoxetine, fluvoxamine and sertraline) have been demonstrated to be efficacious in the treatment of obsessive-compulsive disorder (OCD), but many patients fail to respond to therapy. Treatment-refractory cases are particularly common among the comorbid ASD-OCD group, suggesting that modulation of serotonin alone is not sufficient for symptom relief in this cohort. The hypothesized etiology of childhood-onset OCD suggests that glutamate antagonists, such as riluzole, might reduce the severity of obsessions and compulsions because the drug works "upstream" from current pharmacotherapies. There has been some preliminary success in the use of riluzole for OCD among both adults and children. 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). Four of six pediatric subjects with OCD showed significant improvements after 12 weeks of open-label administration of riluzole; the treatment gains were sustained at one year follow-up with no serious adverse events reported. Compulsions, including simple, repetitive behaviors were improved as much as more complex rituals, suggesting that riluzole might be of benefit for the stereotyped behaviors of autism, as well as for the obsessions and compulsions. Autism spectrum disorders (ASD) are reported to affect as many as 1 in 150 children, with lifelong disabilities affecting social, communication and psychological functioning. With millions of children affected, ASD represents a tremendous public health problem. Compound the ASD symptoms with medical and psychiatric comorbidity, as frequently occurs, and the costs (in both dollars and suffering) are immense. Currently, there are no medications with demonstrated benefits for any of the three core symptoms of autism (social deficits, communication abnormalities and fixated interests/repetitive behaviors). Although some behavioral strategies are reported to be useful for the social and communication spheres, no behavioral interventions have shown consistent benefits for the fixated interests and repetitive behaviors of ASD. However, given the close similarity between these symptoms and the obsessive-compulsive behaviors seen in childhood-onset obsessive-compulsive disorder (OCD), and the frequency with which OCD is present as a comorbidity in ASD, we postulated that medications which reduce OCD symptoms might also improve the repetitive behaviors and fixated interests of ASD. IRB restrictions limited study participants to children and adolescents who had failed to respond to previous therapy with cognitive-behavioral interventions (specifically, exposure with response prevention) and an SSRI. Most participants were taking psychotropic medications at the time of study entry and continued the drugs throughout study participation. Therefore, the trial was limited in its ability to assess safety and efficacy of riluzole for the treatment of obsessive-compulsive symptoms. 60 children and adolescents(ages 7 to 17 years)with OCD completed the 12-weeks double-blind trial. Overall, there were no significant differences between placebo and riluzole for measures of change in OCD or overall symptom severity. Side-effects of riluzole administration were observed, including elevations of liver transaminases. Long-term (1 year) follow-up evaluations revealed that all subjects were improved from baseline, and many had stopped other psychotropic medications in favor of riluzole therapy. However, the lack of between-group differences significantly limits enthusiasm for further investigations of riluzole for childhood-onset OCD.