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Intranasal Esketamine Appears Effective and Relatively Safe for MDD

Key clinical point: In patients with major depressive disorder (MDD), adjunctive intranasal esketamine appears to have an ultra-rapid antidepressant effect at least lasting for 28 days.

Major finding: After a treatment duration of 8-28 days, adjunctive intranasal esketamine was superior to placebo in terms of antidepressant response (risk ratio [RR], 1.39; P less than .0001) and remission (RR, 1.42; P = .0004). Intranasal esketamine vs. placebo had a higher discontinuation rate due to intolerability (RR, 3.50; P = .008); discontinuation rate due to any reason and inefficacy were similar between both groups.

Study details: Meta-analysis of 4 randomized controlled trials with 7 active arms included 708 patients with MDD receiving intranasal esketamine (n=419) or placebo (n=289).

Disclosures: This study was supported by the University of Macau, the Affiliated Brain Hospital of Guangzhou Medical University, and Science and Technology Department of Guangdong Province major science and technology. The authors declared no conflict of interest.


“Intravenous and intranasal esketamine are new rapidly acting treatments for refractory depression. The antidepressant mechanism is unknown but may relate to affinity to multiple receptors: opiate, glutamate (NMDA & AMPA), and/or to boosting neurotrophic factors. Esketamine (S-ketamine), an enantiomer of ketamine, has greater NMDA antagonism than ketamine, a racemic mixture.

This meta-analysis is a useful synthesis of randomized clinical trials so far. Intranasal esketamine appears to be an effective antidepressant over 8 – 28 days. Studies are needed regarding the long-term effectiveness of intravenous and intranasal esketamine given theoretical concerns about the risk of excitotoxic neuronal injury with long term use.”

A Gita Ramamurthy, MD

Director, Psychiatry Consultation-Liaison Service


Zheng W et al. J Affect Disord. 2020 Jan 3. doi: 10.1016/j.jad.2020.01.002.