Glutamate-modulating drugs as novel pharmacotherapeutic agents
in the treatment of obsessive-compulsive disorder

by
Pittenger C, Krystal JH, Coric V.
Yale University Department of Psychiatry,
New Haven, Connecticut 06508, USA.
NeuroRx. 2006 Jan;3(1):69-81.


ABSTRACT

SUMMARY: Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that produces significant morbidity. The introduction of serotonin reuptake inhibitors in the 1980s represented an important advance in the treatment of OCD. However, few patients show complete remission of their symptoms, and some patients show minimal improvement with existing treatments. We review current treatment strategies and initial data supporting the efficacy of glutamate modulating agents as a novel class of pharmaceuticals for the treatment of OCD. Functional neuroimaging studies repeatedly reported metabolic hyperactivity in the cortico-striato-thalamo-cortical circuitry in patients with OCD. Recent magnetic resonance spectroscopy studies provide evidence of elevated glutamate levels in several brain regions in patients suffering from OCD. These findings raised the possibility that agents that reduce glutamate hyperactivity or its consequences in the CNS might be efficacious as novel therapeutic interventions. Indeed, initial evidence from our group suggests that the antiglutamatergic agent riluzole (Rilutek), which was developed for the treatment of amyotrophic lateral sclerosis, is effective in treatment-resistant OCD. Case reports suggest that other agents that modulate glutamatergic activity may likewise be effective. This new application of glutamate modulating agents holds promise for the treatment of this disabling and often inadequately treated disease.
OCD
Glutamate
Riluzole (Rilutek)
NMDA antagonists
Glutamate and GABA
Schizoaffective disorder
Schizophrenia: new drugs
Glutamate and depression
Schizophrenia: neuroleptics
Serotonin hypothesis of schizophrenia
Dopamine hypothesis of schizophrenia
Glutamate-modulating drugs for mood disorders

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