How do ketamine and esketamine help depression, and how durable are the benefits?

Ketamine and esketamine act on the brain’s glutamate system, including NMDA receptors, rather than working primarily by blocking serotonin reuptake. The precise chain producing antidepressant benefit is not fully established. Ketamine contains two mirror-image forms of the molecule; esketamine is one of them. They can produce rapid improvement in some patients, but the treatments are not interchangeable by route or formulation. In the United States, supervised intranasal esketamine has specific depression indications, while ketamine’s use for depression is off-label. An at-home compounded product is not the same intervention as an approved esketamine program.[1][2]

A rapid response is not necessarily a lasting remission after one session. In a randomized relapse-prevention trial, patients who had already responded to esketamine plus an oral antidepressant were less likely to relapse if they continued esketamine than if it was replaced with placebo spray. Because these were selected responders, the finding does not describe everyone starting treatment. Maintenance planning and follow-up matter. Sedation, dissociation, increased blood pressure, respiratory effects and misuse potential are reasons for clinical screening and monitoring, rather than viewing these drugs as general mood or productivity enhancers.[1][3]