[Combination of ketamine and esketamine with Exposure and Response Prevention (ERP) therapy for Obsessive-Compulsive Disorder].

Obsessive-Compulsive Disorder (OCD), characterized by the combination of obsession and compulsion, is a clinical and therapeutic challenge. Many patients with OCD do not respond to first-line treatments such as serotonin selective reuptake inhibitors (SSRIs) and exposure and response prevention psychotherapy (ERP). For these resistant patients, some preliminary studies have shown that ketamine, a non-selective glutamatergic NMDA receptors antagonist, could improve the obsessive symptoms. A number of these studies have also suggested that the combination of ketamine with ERP psychotherapy may jointly potentiate the effectiveness of ketamine and ERP. In this paper, we present the existing data on the combined use of ketamine with ERP psychotherapy for OCD. We suggest that modulation of NMDA receptor activity and glutamatergic signaling by ketamine may promote the therapeutic mechanisms involved in ERP such as fear extinction and brain plasticity mechanisms. Finally, we propose a ketamine-augmented ERP psychotherapy (KAP-ERP) protocol in OCD, and we present the limitations associated with its application in clinical practice.