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. During the study period, data collection was completed for a 12-weeks long, placebo-controlled investigation assessing safety and efficacy of riluzole for the treatment of obsessive-compulsive symptoms among 60 children and adolescents(ages 7 to 17 years)with OCD, up to 30 of whom also had ASD. Data analysis is currently underway and it is expected that we will find riluzole to be superior to placebo in reducing obsessive-compulsive symptom severity, and possibly the frequency and intensity of ASD-related stereotyped behaviors and fixated interests. Overall behavior is also expected to improve. A study of the neurochemical effects of riluzole treatment is underway, utilizing magnetic resonance spectroscopy (MRS). Children and adolescents who participate in the investigation will undergo an MRS scan (similar to an MRI scan) before starting treatment with riluzole and during treatment. Changes in brain concentrations of glutamate and related chemicals will be assessed and compared with symptom severity and degree of treatment response. The MRS study is currently recruiting subjects and further information about the investigation can be found at ClinicalTrials.gov with study identifier: NCT01019967

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2011
Total Cost
$352,969
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
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State
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