Ketamine in depression and electroconvulsive therapy

A rapid antidepressant effect of low-dose ketamine and its enantiomer esketamine has been proven conclusively. A single intravenous infusion of 0.5 mg/kg of ketamine or a single intranasal dose of esketamine produces antidepressant and antisuicidal effects within hours, lasting up to a week. Repeated nasal esketamine is considered to prevent relapse, though longitudinal studies are insufficient. The antidepressant mechanism is thought to be mediated by improved neuroplasticity in cortico-limbic brain areas. This research has led to a neurotrophic concept of depression. Further studies are needed on safety and efficacy of repeated administration.

Study at a glance

Abstract

Purpose of review The antidepressant effect of subanesthetic doses of ketamine was recognized 20 years ago. This review briefly summarizes the current understanding of the antidepressant mechanisms and the available clinical research on the use of racemic ketamine and enantiomer esketamine for depression. Recent findings The antidepressant effect of subanesthetic doses of ketamine is currently considered to be predominantly mediated by improved neuroplasticity in cortico-limbic areas in the brain. Single dose of 0.5 mg/kg of ketamine infused intravenously over 40 min, or single intranasal dose of esketamine cause rapid antidepressant and antisuicidal effects within hours of administration, and the antidepressant effect may last up to a week. Repeated administration of nasal spray esketamine is considered to prevent relapse of depression. Longitudinal studies are currently insufficient. When used in various doses for anesthetic induction for electroconvulsive therapy, ketamine improves seizure quality and may possibly diminish posttherapy cognitive impairment. Summary A rapid onset antidepressive effect of ketamine and esketamine has been proven conclusively. The results of extensive basic science research of the mechanism of action of low-dose ketamine doses has led to an alternative hypothesis of the pathophysiology of depression and the development of a novel neurotrophic concept of depression. Further longitudinal studies are warranted to determine the safety and efficacy of repeated administration of ketamine and its analogs to prevent relapse and recurrence of depression.