Ketamine and esketamine show potential for treating treatment-resistant depression and improving certain cognitive functions, though effects depend on dose and duration. Randomized controlled trials indicate that a 0.5 mg/kg ketamine infusion improves visual memory, processing speed, working memory, and attention in patients who respond. However, long-term ketamine use may harm spatial working memory. Esketamine, an NMDA receptor antagonist, provides rapid antidepressant effects and stabilizes or improves cognition, but high doses may be neurotoxic and impair cognition. Both drugs require more research on long-term safety.
Many individuals with major depressive disorder do not respond adequately to standard antidepressants, which also have a delay of weeks before therapeutic effects emerge. Recent studies show that a subanesthetic dose of ketamine is efficacious and safe for treating depression, though its antidepressant effects are short-lived. Psychotomimetic properties may limit ketamine's use in depressive patients. Future research should focus on identifying predictors of response, investigating different doses and routes of administration, and maintaining the antidepressant effect.