Ketamine given intravenously rapidly reduces depressive symptoms, with effects lasting at least a week. In an analysis of 17 randomized controlled trials with 809 participants, the benefit over placebo was larger for patients who had already failed two or more prior antidepressant trials. However, no patient-level clinical or demographic characteristics—such as age, sex, or diagnosis—could predict who would respond best, limiting the ability to personalize ketamine prescriptions. The findings confirm ketamine's broad effectiveness for depression but show that precision medicine approaches cannot yet guide treatment decisions.
Combining six ketamine infusions with a brief exposure-based psychotherapy, written exposure therapy (WET), produced large and durable reductions in PTSD symptoms for patients with chronic, severe PTSD. In an open-label trial, 13 of 14 patients completed treatment. PTSD symptom severity, measured by the CAPS-5, dropped from an average of 41.6 before treatment to 20.8 at 12 weeks, a large-magnitude improvement. Nine patients (69%) were treatment responders, and eight (61.5%) maintained improvement up to six months. The authors suggest the combined treatment may be effective but call for larger randomized controlled trials to confirm efficacy and synergy.