Ketamine-Assisted Psychotherapy Provides Lasting and Effective Results in the Treatment of Depression, Anxiety, and Post-Traumatic Stress Disorder at 3 and 6 Months: Findings from a Large Retrospective Effectiveness Study.

Ketamine-assisted psychotherapy (KAP) produces sustained reductions in anxiety, depression, and PTSD symptoms lasting up to 5 months after the last session. In a retrospective study of adults with treatment-resistant major depressive disorder, generalized anxiety disorder, or PTSD who received KAP across 11 North American clinics, large treatment effects were detected at 3 months (Cohen's d = 0.75-0.86) and sustained at 6 months (d = 0.61-0.73). Case reductions ranged from 39% to 41% at 3 months and 29% to 37% at 6 months. However, high attrition rates (82% at 3 months, 95% at 6 months) may limit validity of the results.

Study at a glance

Abstract

Ketamine-assisted psychotherapy (KAP) is an emerging treatment option to alleviate treatment-resistant affective disorders, but its long-term effectiveness remains unclear. To examine the treatment effects of KAP on anxiety, depression, and post-traumatic stress disorder (PTSD) at 1, 3, and 6 months post-treatment. This retrospective effectiveness study included self-reported outcomes from adults with a history of major depressive disorder, generalized anxiety disorder (GAD), or PTSD who had not responded to prior treatment interventions and received KAP administered across 11 Field Trip Health clinics in North America between March 13, 2020, and June 16, 2022. The evaluable sample sizes were 346 and 94 participants at 3 and 6 months, respectively, representing loss to follow-up rates of 82% and 95%. KAP consists of 4-6 guided ketamine sessions (administered through intramuscular injection or sublingual lozenge) with psychotherapy-only integration visits after doses 1 and 2 and then after every 2 subsequent doses. Mean number of doses administered was 4, standard deviation (SD) = 3, and mean number of integration sessions was 3, SD = 2. Primary outcomes were changes in symptoms of depression, anxiety, and PTSD at 3 months relative to baseline, assessed, respectively, using the 9-item Patient Health Questionnaire, the 7-item GAD measure, and the 6-item PTSD checklist. Secondary outcomes were changes at 1 and 6 months relative to baseline. Large treatment effects were detected at 3 months (d's = 0.75-0.86) and were sustained at 6 months (d's = 0.61-0.73). Case reductions (identified based on cutoff values) ranged from 39% to 41% at 3 months and 29% to 37% at 6 months. In total, 50-75% reported a minimal clinically important difference at 3 months and 48-70% at 6 months. KAP produced sustained reductions in anxiety, depression, and PTSD, with symptom improvement lasting well beyond the duration of dosing and integration sessions. These effects extended to as much as 5 months after the last KAP session. However, the high rates of attrition may limit validity of the results. Given the growing mental health care crises and the need for effective therapies and models of care, especially for intractable psychiatric mood-related disorders, these data support the use of KAP as a viable alternative. Further prospective clinical research should be undertaken to provide evidence on the safety and effectiveness of ketamine within a psychotherapeutic context.