Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Dec 22;11(1):6431.
doi: 10.1038/s41467-020-20190-4.

The role of dissociation in ketamine's antidepressant effects

Elizabeth D Ballard  1 , Carlos A Zarate Jr  2
Affiliations
Review

The role of dissociation in ketamine's antidepressant effects

Elizabeth D Ballard et al. Nat Commun. .

Abstract

Ketamine produces immediate antidepressant effects and has inspired research into next-generation treatments. Ketamine also has short term dissociative effects, in which individuals report altered consciousness and perceptions of themselves and their environment. However, whether ketamine's dissociative side effects are necessary for its antidepressant effects remains unclear. This perspective examines the relationship between dissociative effects and acute and longer-lasting antidepressant response to ketamine and other N-methyl-D-aspartate (NMDA) receptor antagonists. Presently, the literature does not support the conclusion that dissociation is necessary for antidepressant response to ketamine. However, further work is needed to explore the relationship between dissociation and antidepressant response at the molecular, biomarker, and psychological levels.

PubMed Disclaimer

Conflict of interest statement

C.A.Z. is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydro and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. E.D.B. has no competing interests.

References

    1. Malhi GS, Morris G, Bell E, Hamilton A. A new paradigm for achieving a rapid antidepressant response. Drugs. 2020;80:755–764. doi: 10.1007/s40265-020-01303-1. - DOI - PubMed
    1. Zarate CA, Jr., et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch. Gen. Psychiatry. 2006;63:856–864. doi: 10.1001/archpsyc.63.8.856. - DOI - PubMed
    1. Domino EF, Chodoff P, Corssen G. Pharmacologic effects of Ci-581, a new dissociative anesthetic, in man. Clin. Pharm. Ther. 1965;6:279–291. doi: 10.1002/cpt196563279. - DOI - PubMed
    1. Berman RM, et al. Antidepressant effects of ketamine in depressed patients. Biol. Psychiatry. 2000;47:351–354. doi: 10.1016/S0006-3223(99)00230-9. - DOI - PubMed
    1. Murrough JW, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am. J. Psychiatry. 2013;170:1134–1142. doi: 10.1176/appi.ajp.2013.13030392. - DOI - PMC - PubMed

Publication types

MeSH terms