A pilot case series tested an eight-week program combining nasally administered ketamine (0.5 mg/kg) with trauma-focused psychotherapy for three individuals with chronic, treatment-resistant PTSD. Clinically relevant reductions in PTSD symptoms were observed, with CAPS-5 scores decreasing by an average of 18 points after treatment and 25 points at follow-up. Depressive symptoms also improved, with HAMD scores dropping by an average of 8.3 points after treatment and 9 points at follow-up. Additional benefits included reduced anxiety, fewer dissociations, and better emotion regulation. The ketamine was well tolerated and provided immediate relief from tension, anxiety, and common PTSD symptoms. The authors note that randomized controlled trials are needed to validate these findings.
A systematic review and individual participant data meta-analysis of 12 studies (533 participants) found that higher baseline PTSD severity was the most robust predictor of symptom reduction after combined ketamine and psychotherapy. More psychotherapy sessions, more ketamine sessions, and shorter treatment duration were also associated with greater improvement, but these findings are tentative because most studies were of poor quality. The analysis showed that for each additional psychotherapy session, PTSD symptoms improved by an average of 1.03 points on the PCL-5, and for each additional ketamine session, improvement was 1.15 points. The results require confirmation in well-designed prospective trials.