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.
Nitrous oxide (N2O) has been used since the 1700s and today is a significant greenhouse gas and ozone-depleting substance, though medical use contributes little to these effects. Its analgesic and anesthetic properties make it common in dentistry and surgery, and new research suggests antidepressant actions through NMDA antagonism and opioid effects. Larger clinical trials are needed to confirm its use as a rapid-acting antidepressant, and optimal dosing and duration remain unclear. Non-medical use has increased, with risks including asphyxia from acute use and vitamin B12 deficiency from chronic use, leading to conditions like megaloblastic anemia, venous thrombosis, myeloneuropathy, and skin pigmentation. Treatment requires stopping N2O use and administering parenteral vitamin B12; homocysteine and methylmalonic acid are helpful diagnostic tests.