The Use of Glutamate Modulating Drugs in Obsessive Compulsive Disorder

Abstract

Obsessive-compulsive disorder (OCD) is a chronic, severe and debilitating disorder, affecting over 3 million people in the United States. People afflicted with OCD have obsessions and compulsions that impair their functioning in life. According to the World Health Organization, OCD is among the ten most disabling medical conditions worldwide. The National Comorbidity Survey Replication, when examining anxiety disorders, found that OCD had the highest percentage of serious cases (50.6%) (Kessler et al., 2005). Lifetime prevalence estimates of OCD in pediatric and adult populations range from 1% to 3% (Kessler et al., 2005). The clinical presentation of OCD in childhood and adulthood is similar, making findings applicable across the age span. The mean age of onset for OCD in children is between 9 to 11 years in males and 11 to 13 years in females (Hanna, 1995). A more negative outcome is associated with an early age of onset. Furthermore, pediatric OCD was found to be chronic and unremitting in up to 87% of cases that failed to receive effective treatment (Stewart et al., 2004). Finally, an early diagnosis of OCD is associated with a higher risk for developing other psychiatric disorders into adulthood. THE CASE FOR NOVEL TREATMENTS OF OCD Serotonin reuptake inhibitors (SRI) are the only FDA approved medications for OCD. While considered effective in the clinical trial literature, treatment of OCD with SRI’s has proven limited in clinical practice. SRIs are only effective in 40 to 60% of patients (Jenike, 2004). Obviously, this leaves a considerable number still ill. Additionally, studies often define treatment response as a 20 to 40% reduction in symptoms. Hence, many subjects who are classed as “responders” still have marked symptoms after treatment (Jenike, 2004). OCD symptom severity scores, as calculated by the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), normally range from 15 to 20 post-treatment. A score in this range is still indicative of significant impairment. In addition to SRIs, cognitive behavioral therapy (CBT), alone or in combination with SRI, is also considered effective for treating OCD (POTS, 2004). Nonetheless, one-third of pediatric patients remain markedly ill even after receiving the combination of CBT and medication (POTS, 2004). What is more, data indicates that an earlier onset of OCD may be associated with the illness being more treatment refractory (POTS, 2004). Indeed, OCD is one of the few remaining psychiatric disorders for which there is a neurosurgical treatment indication. The persistence of symptoms and the limited nature of treatment response indicates that the serotonin paradigm of understanding OCD cannot fully account for the underlying neurobiology of the illness. Therefore, novel, evidence based approaches are needed to advance treatment of OCD. The glutamate hypothesis of OCD, first developed over a decade ago (Rosenberg & Keshavan, 1998), and resulting biological evidence has recently translated to the application of glutamate modulating agents for the treatment of pediatric OCD.