Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders

Obsessive-Compulsive Disorder (OCD) is a chronic psychiatric disorder characterized by the
presence of intrusive and unwanted obsessional thoughts and images and of compulsive
behaviors. Its presentation during childhood is similar to that seen in adulthood, except
that children sometimes lack insight into the senselessness of the thoughts and behaviors.
Although many patients benefit from treatment with selective serotonin reuptake inhibitors
(SSRIs), a significant proportion have limited or no response to these medications.
Additionally, these medicines have been associated with a slight but significant increase in
onset of suicidal thoughts among adolescents being treated for depression or OCD. Cognitive
behavioral therapy (CBT) may also be effective for OCD, alone or in combination with SSRIs,
but there is a shortage of qualified therapists, and many patients and families cannot
participate effectively in the therapy. Further, in a recent report on a multi-site study
of childhood OCD, CBT alone at one site fared little better than placebo.

There is a pressing need, then, for the development of alternative, novel treatments for
pediatric OCD. Neuropsychological and neuroimaging data suggest that OCD may arise from
dysfunction of orbitofronto-striato-thalamocortical circuitry. Glutamate plays a crucial
role in the regulation of excitatory activity within this circuit and may be involved in the
etiopathogenesis of OCD. If so, then agents which reduce glutamatergic neurotransmission
may provide unique antiobsessional benefits. Riluzole is a medication that reduces
glutamatergic activity. It is currently being studied in adults with OCD, and this
two-stage study will evaluate the possibility that riluzole will help children with OCD,
Riluzole has been approved by the Food and Drug Administration (FDA) for treatment of
amyotrophic lateral sclerosis (ALS), and is currently under investigation at the NIMH for
treatment of depression.

The first stage of this investigation has been completed. Six children with OCD, ages 7 to
17 years, received riluzole as part of a study that evaluated the drug's safety and
estimated the appropriate dose of riluzole Riluzole was added to the children's current
medication regimen or was used as sole agent. The second stage of the investigation will
enroll up to 60 additional subjects with OCD including some who have both autistic spectrum
disorder (ASD) and OCD. The subjects will participate in a double-blind,
placebo-controlled12-week trial of riluzole as a sole agent or as an augmentation to their
currently inadequate therapy. Following the double-blind portion of the trial, subjects may
receive three months of open-label treatment with riluzole, if it is clinically indicated.
All subjects will be followed at regular intervals until one year from baseline.