In an open-label retrospective analysis of 35 Veterans with co-occurring depression and PTSD, repeated intranasal (S)-ketamine treatments over four weeks were associated with reductions in both depression and PTSD symptoms. Depression scores on the PHQ-9 fell by an average of 5.1 points, from 19.8 to 14.7, with 14% of patients showing a clinically meaningful response. PTSD scores on the PCL-5 dropped by an average of 15.5 points, from 54.8 to 39.3, with 46% showing a clinically meaningful response. Changes in depression and PTSD symptoms were only moderately correlated, and some individuals experienced PTSD improvement without antidepressant response, suggesting distinct mechanisms of action for the two conditions.
MDMA-assisted psychotherapy shows promise for treating PTSD, but the FDA rejected its current form due to concerns about standardization and empirical grounding of the psychotherapy methods. Acceptance and Commitment Therapy (ACT), an evidence-based cognitive behavioral therapy, is proposed as a well-suited alternative to pair with MDMA. The subjective effects of MDMA directly support key ACT processes; ACT methods could prepare patients for MDMA administration, guide therapists during sessions, and help integrate MDMA experiences to improve functioning and quality of life. ACT offers a scalable, structured yet flexible framework for a new PTSD treatment approach.