Exploring Glutamate Augmentation as a Novel OCD Treatment: A Comparison Between Risperidone and Memantine as SSRI Adjunctive Therapies

Obsessive Compulsive Disorder (OCD) is a chronic neuropsychiatric disorder characterized by the presence of either obsessions, compulsions, or both. The current FDA-approved treatments for OCD primarily target the serotonergic system and only yield therapeutic effects for ~70% of OCD patients. Thus, augmentation treatments are used to enhance the effects of serotonergic monotherapy or to target additional neurotransmitters, particularly in treatment-resistant patients. Notably, emerging research on glutamate's role in OCD pathology shows promising results for the use of glutamate-modulating medications as SSRI augmentation treatments. This study compares the efficacy of two augmentation treatments: a common treatment using the serotonin and dopamine-modulating medication Risperidone, and a novel treatment using the glutamate-modulating medication Memantine. A PICOS analysis including ten double-blind, randomized, placebo-controlled studies was conducted to compare the efficacy of both medications on OCD symptoms. There were no significant differences between Risperidone and Memantine treatments, though there was a trend towards significance favouring the effectiveness of Memantine. These results indicate that Memantine and Risperidone produce similar effects in the reduction of OCD symptoms, supporting the potential use of Memantine as an augmentation therapy for SSRI-resistant and antipsychotic-augmentation-resistant OCD patients. Further research must be conducted to characterize the potential of novel glutamate-modulating medications for OCD treatment.