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

Abstract Background Antidepressant effects of ketamine and esketamine are short lived, often lasting only weeks after multiple treatments. With that in mind, it has been considered addition of psychotherapy may enhance outcomes. One approach, knows as Ketamine Assisted Psychotherapy (KAP) focuses on "integration " of the dissociative experience induced by ketamine, and suggests this may produce better effects and/or more lasting changes. Alternatively, existing psychotherapies such as cognitive behavioral therapy (CBT), conducted in ordinary, unmedicated states may extend ketamine’s response if done in parallel to ketamine administration. These approaches differ significantly, but have both been reported in the literature as KAP, which may conflate the existing evidence base. Members of our group have previously highlighted these differences and have strongly suggested the use of different terms for each model to support clarity. More specifically, psychotherapies where ketamine’s dissociative or psychedelic effects are considered central to a therapy process could be considered KAP. On the other hand, psychotherapy modalities, such as CBT, that do not require ketamine’s dissociative experience could more accurately be described as Ketamine Combined with Psychotherapy (KCP). As it has been previously established that combining psychotherapy with pharmacotherapy improves outcomes in depression, it is important to separate these treatment approaches to accurately evaluate and discuss KAP treatment approaches. Aims & Objectives This scoping review comprehensively maps the existing evidence combining use of ketamine/esketamine and psychotherapy for depressive disorders or depressive symptoms, and categorizes treatment models as KAP and KCP as per proposed definitions. Methodological and conceptual gaps are identified.

Method: A scoping review was conducted on studies including on adult patients with depressive disorders or depressive symptoms, as long as if the treatment intervention included ketamine or esketamine and psychotherapy. All doses and modes of drug administration were included, and all forms of psychotherapy were included. All empirical study types were included; including randomized controlled trials, observational studies, cohort studies, case-control studies, retrospective case series, and individual case reports. Case series and case reports were included to capture early experiential evidence and emerging clinical practices. Studies are categorized as KCP or KAP.

Results: KAP studies are limited to one open label trial, 11 observational/retrospective reports, and 8 individual case reports. KCP studies included 3 randomized controlled trials(RCTs), 1 open label trial, 4 observational/retrospective reports, and 1 individual case report. Three observational studies used both KAP/KCP, and 4 studies could not be categorized. There was much heterogeneity in reporting. Discussion & Conclusions At this time, limited data support efficacy of KCP for depression. Current data do not support the rising popularity of KAP to treat depression. Positive outcomes of KAP studies could not be separated from the pharmacologic antidepressant effects of ketamine or esketamine. Future studies should include comparison groups with and without psychotherapy. When KAP data is reported, it should include the type and timing of psychotherapy, and a description of the intended dissociative effects and their role in therapy,