Ketamine provides rapid but short-lived antidepressant effects. In an open-label trial, patients with treatment-resistant depression received a 2-week course of intravenous ketamine alongside a 10-week course of cognitive behavioral therapy (CBT). Of 16 participants, 8 responded to ketamine and 7 achieved remission in the first 2 weeks. Among responders, 25% relapsed by the end of CBT, and the median time to relapse was 12 weeks after ketamine. Among remitters, 2 of 7 maintained remission through 8 weeks after ketamine. Ketamine nonresponders did not benefit from CBT. The combination may help sustain ketamine's effects, but randomized controlled trials are needed.
Ketamine represents a new type of antidepressant that works quickly, helps people whose depression has not responded to other treatments, and reduces the chance of relapse. Its development came from a new understanding of depression's biology, and studying how ketamine works has deepened knowledge of depression and related conditions. Twenty-five years after the first findings on ketamine for depression were presented, this review examines what has been learned and suggests future ways to improve rapid-acting antidepressant therapy.