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 single-arm retrospective effectiveness trial

Ketamine-Assisted Psychotherapy (KAP) produced large and sustained reductions in depression, anxiety, and PTSD symptoms for up to six months after treatment. In a retrospective trial of 1806 adults with treatment-resistant depression, anxiety, or PTSD, effect sizes at three months ranged from 0.75 to 0.86 and were maintained at six months (0.61 to 0.73). Between 39% and 41% of patients showed case reductions at three months, and 29% to 37% at six months. A minimal clinically important difference was reported by 50% to 75% at three months and 48% to 70% at six months. The treatment involved 4 to 6 guided ketamine sessions with psychotherapy.

Study at a glance

Abstract

Abstract IMPORTANCE Ketamine-Assisted Psychotherapy (KAP) is an emerging treatment option to alleviate treatment resistant affective disorders, but its long term effectiveness remains unclear. OBJECTIVE To examine the treatment effects of KAP on anxiety, depression, and post traumatic stress disorder (PTSD) at 1, 3, and 6 months post treatment. DESIGN, SETTING, AND PARTICIPANTS This retrospective single-arm effectiveness trial included self-reported outcomes from 1806 adults with a history of depression, anxiety, 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. INTERVENTION KAP consisting of 4-6 guided ketamine sessions (administered via intramuscular injection or sublingual lozenge) with psychotherapy-only visits after doses 1 and 2 and then after every 2 subsequent doses. Mean number of doses administered was 4, SD=3, and mean number of psychotherapy sessions was 3, SD=2. MAIN OUTCOMES AND MEASURES Primary outcomes were changes in depression, anxiety, and PTSD at 3 months relative to baseline, assessed respectively using the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder measure (GAD-7), and the 6-item PTSD Checklist (PCL-6). Secondary outcomes were changes at 1 and 6 months relative to baseline. RESULTS Large treatment effects were detected at 3 months (d’s=0.75-0.86) that were sustained at 6 months (d’s=0.61-0.73). Case reductions (identified based on cut-off values) ranged from 39-41% at 3 months and 29-37% at 6 months. 50-75% reported a minimal clinically important difference at 3 months and 48-70% at 6 months. CONCLUSIONS AND RELEVANCE KAP produced sustained reductions in anxiety, depression, and PTSD, with symptom improvement lasting well beyond the duration of dosing sessions. These effects extended to as much as 5 months after the last KAP session. 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 would support the consideration of KAP as a viable alternative. Further prospective clinical research should be undertaken to provide further evidence on the safety and effectiveness of ketamine within a psychotherapeutic context. TRIAL REGISTRATION Clinicaltrials.gov Identifier NCT05604794 Key Points Question What are the lasting effects of Ketamine-Assisted Psychotherapy on psychological distress? Findings In this retrospective single-arm effectiveness trial that included 1806 adults, there were large effect sizes at 3 months on depression, anxiety, and post traumatic stress (d’s=0.75-0.86) that were sustained at 6 months. Meaning These findings suggest that Ketamine-Assisted Psychotherapy is an effective treatment option with substantial clinical benefits detected up to half a year.