A systematic review found no clinical studies directly testing whether ketamine or esketamine can improve neurological rehabilitation in humans through their neuroplastic effects. Preclinical animal models of traumatic brain injury and ischemic stroke show that these drugs reduce neuroinflammation, excitotoxicity, and oxidative stress, and support structural neuroplasticity, correlating with improved sensorimotor and behavioral outcomes. The authors conclude that ketamine and esketamine are promising adjunctive agents for neurological rehabilitation, but insufficient clinical evidence exists to formulate official recommendations. Well-designed randomized controlled trials with long-term follow-up are needed to confirm efficacy and safety.
Combining ketamine with structured psychotherapies such as cognitive-behavioral therapy, behavioral activation, or automated computer training of implicit self-associations may moderately extend the drug's short-lived antidepressant effects in treatment-resistant depression, though the data are mixed. One study found no clear benefit of adding computer training to ketamine alone. The proposed mechanism relies on a ketamine-induced window of heightened neuroplasticity that could help consolidate new cognitive-emotional and behavioral patterns. Current evidence is insufficient to establish standardized protocols, and larger randomized controlled trials are needed to confirm how much psychotherapy contributes to prolonging ketamine's antidepressant efficacy.