Glutamatergic agents for OCD and related disorders

Pharmacotherapy remains inadequate for many patients with obsessive-compulsive disorder (OCD); there is an urgent need for alternative pharmacological strategies. Convergent evidence suggests imbalance in glutamate, the brain’s primary excitatory neurotransmitter, in some patients. This has motivated interest in glutamate modulators in patients who are unresponsive to standard pharmacotherapeutic approaches. While no glutamate modulator can be considered proven as an efficacious treatment of OCD, promising suggestions of benefit have been reported for memantine and riluzole. The evidence is thinner for N-acetylcysteine, but this agent’s low cost and benign side effect profile make it a reasonable consideration in certain patients. Intriguing research on d-cycloserine and ketamine suggest potential benefit as well. It is notable that these agents all work by different, and in some cases opposite, mechanisms; this suggests that we have much to learn about the role of glutamate dysregulation in the etiology of OCD and of glutamate modulators in its treatment.