The Efficacy of Ketamine Augmentation on Treatment-Refractory Obsessive-Compulsive Disorder: A Double-Blind Placebo-Controlled Clinical Trial

Introduction: Abnormalities occurring in the glutamatergic system during obsessive-compulsive disorder, as a debilitating mental health condition, have been thus far illustrated. However, open-label and clinical trials of ketamine augmentation in limited subjects with treatment-refractory Obsessive- Compulsive Disorder (OCD) have not documented very persistent anti-OCD effects. Therefore, this controlled trial was conducted on patients with treatment-refractory OCD to evaluate the therapeutic efficacy of ketamine augmentation, as a non- competitive N-methyl-D-aspartate receptor antagonist.Method: In this prospective, double-blind, placebo-controlled clinical trial, a total number of 30 subjects with treatment-refractory OCD were randomly assigned to either the group with the intravenous infusion of ketamine 0.5 mg/kg or the one receiving a dose of midazolam 0.045 mg/kg as an active placebo over 40 min. The OCD Visual Analog Scale (OCD- VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were also performed at mid-infusion, 1 h later, and on the 1st, 3rd, 5th, 7th, 14th, 21st, and 28th days following it. Results: The mean OCD-VAS score in the group taking ketamine was lower than the value in the group receiving midazolam during the treatment. Even though these differences were not significant, the trend of changes in each study group was considerable (P=0.001). Response to treatment in the ketamine group was significantly higher than the midazolam group on the third day of treatment (P=0.042).Conclusion: According to the findings of the present study, it can be stated that the adjuvant therapy with ketamine could bring significant positive effects on the third day of the treatment.