A scoping review: ketamine or esketamine when used to assist psychotherapy or in combination with psychotherapy for the management of depression in adults

This scoping review maps literature for use of ketamine or esketamine with psychotherapy for depression or depressive symptoms. Forty-seven studies were identified including 4/47 (9%) randomized controlled trials, 4/47 (9%) open label trials, 27/47 (57%) observational or retrospective studies, and 12/47 (26%) individual case reports. Studies were categorized as Ketamine/Esketamine Combined with Psychotherapy (KCP/ES-CP), where an altered state is not necessary for psychotherapy, or Ketamine/Esketamine Assisted Psychotherapy (KAP/ES-AP), where an altered state and/or integration of the experience is central to the psychotherapy. The 47 included 23/47(49%) KAP, 1/47 (2%) ES-AP, 7/47 (15%) KCP, 3/47 (6%) ES-CP, 8/47 (17%) dual KAP/KCP and 1/47 (2%) dual ES-KAP/ES-CP. Four studies could not be categorized. Separation into these categories was useful to more clearly report current state of the literature. Though previous reviews have suggested KAP is of benefit for depression, KAP studies were limited by lack of RCTs, lack of comparison groups without psychotherapy, and a large number of individual case reports. To date, fewer studies, but higher quality data support a KCP model, with 3 studies suggesting benefit to combining ketamine with cognitive behavioral therapy (CBT). Further, high quality research including accurate reporting and description of psychotherapy model is required.