Therapeutic Protocols Using Ketamine and Esketamine for Depressive Disorders: A Systematic Review

Depression is one of the most prevalent mental health disorders globally, causing severe emotional suffering, reducing life expectancy and increasing the risk of suicide. Recently, the use of dissociative psychedelic substances such as ketamine and esketamine for depressive disorders has expanded treatment options. We sought to analyze, through a systematic review, the existing protocols for the treatment of depression with ketamine and esketamine. The search adopted PRISMA criteria and was performed using PubMed and Web of Science databases. Procedures in each study were compared, focusing on the sample recruited, therapeutic approaches, including the clinical team and professionals engaged in treatment, medical procedures, description of the setting (including music) and factors such as specific medication (ketamine or esketamine), route of administration and dosage employed. Results indicated the predominance of a medical approach, with a limited number of studies on ketamine assisted psychotherapy (KAP) and other modalities of psychedelic assisted therapy. Additionally, there is limited information on psychosocial elements such as preparation, psychological support during session and integration of experience. Altogether these findings suggest that treatment of depression with ketamine or esketamine diverges in relation to the practices employed with psychedelic substances. This is discussed considering future research directions in the field.