Ketamine alone and ketamine combined with psychotherapy both rapidly reduce depression and PTSD symptoms, with no significant difference between the two approaches over 30 or 180 days. Analyzing overlapping samples of 202, 470, and 624 help-seeking individuals (about 60% female, average age 42) who received either ketamine alone or ketamine plus psychotherapy across 4 to 14 sessions, both groups showed substantial improvement with rapid initial decline followed by stabilization. Exploratory patterns suggested younger females may benefit more from combined treatment, while older males may do better with ketamine alone, but these differences were not statistically significant. Ketamine's effects appear robust enough that adding psychotherapy during acute treatment does not enhance outcomes, though longer-term benefits warrant further study.
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.