Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms

Summary

Ketamine, a drug that blocks NMDA receptors in the brain, produces rapid antidepressant effects in people with depression and treatment-resistant depression. This finding has led to new treatments for mood disorders and has advanced understanding of the brain's neurobiology and the synaptic plasticity mechanisms that make ketamine effective. This review covers the clinical aspects of ketamine's rapid antidepressant action, the synaptic and circuit mechanisms behind it, and how these insights can guide future research toward more effective treatments for neuropsychiatric disorders.

Study at a glance

Abstract

Ketamine is an open channel blocker of ionotropic glutamatergic N -Methyl- D -Aspartate (NMDA) receptors. The discovery of its rapid antidepressant effects in patients with depression and treatment-resistant depression fostered novel effective treatments for mood disorders. This discovery not only provided new insight into the neurobiology of mood disorders but also uncovered fundamental synaptic plasticity mechanisms that underlie its treatment. In this review, we discuss key clinical aspects of ketamine’s effect as a rapidly acting antidepressant, synaptic and circuit mechanisms underlying its action, as well as how these novel perspectives in clinical practice and synapse biology form a road map for future studies aimed at more effective treatments for neuropsychiatric disorders.