Ketamine Augmentation of Exposure Response Prevention Therapy for Obsessive-compulsive Disorder

Obsessive-compulsive disorder (OCD) is a disabling disease characterized by intrusive thoughts, with compulsions performed to lessen distress. Many patients with OCD do not respond to first-line intervention, such as serotonin reuptake inhibitors (SRIs) and exposure and response prevention (ERP) therapy. Previous studies have focused on the use of ketamine, a nonselective N-methyl D-aspartate receptor (NMDAR) antagonist, for treatment-resistant OCD. Research has shown that ketamine modulates NMDARs and gamma-aminobutyric acid receptors (GABAR), which are major pathways for contingency-learning, belief updating, and extinction learning. Here, we propose an augmented psychotherapy (AP) protocol combining ERP intervention with administration of ketamine. We describe the theory that NMDAR modulation might directly promote the therapeutic mechanisms involved in exposure and discuss the possibility that ketamine plasticity enhancement might potentiate extinction-based psychotherapy in the treatment of OCD.