Ketamine, a glutamate-based antidepressant, can rapidly alleviate depression within hours of treatment. Replicated evidence shows its rapid and potent effects in treatment-resistant depression. Preclinical and biomarker studies have begun to explain the mechanism behind these rapid effects, offering new insights into depression's biology and identifying potential treatment targets. This article discusses ketamine's efficacy, safety, and tolerability, summarizes depression's neurobiology, reviews the mechanisms of ketamine's rapid antidepressant effects, and considers prospects for next-generation rapid-acting antidepressants.
Ketamine produces rapid and sustained antidepressant effects in patients with major depressive disorder that has not responded to conventional monoamine-based drugs. Recent preclinical studies have begun to clarify the mechanisms underlying these effects. This review compares clinical and preclinical findings to provide a broad perspective on how ketamine works as an antidepressant.
Depressive disorders impose a heavy global public health burden, with a gap between how common they are and the availability of fast, effective treatments that lead to remission. Brexanolone and zuranolone, the first FDA-approved drugs for postpartum depression, mark a critical advance for a vulnerable patient group. Psilocybin shows promise for treatment-resistant depression and for people who have not found relief with existing options. This review discusses these transformative therapies as major steps forward for postpartum depression, major depressive disorder, and treatment-resistant depression.