Role of nitric oxide signaling in the antidepressant mechanism of action of ketamine: A randomized controlled trial

Laura Bevilacqua, Alex Charney, Charlotte R. Pierce, Samantha M. Richards, Manish K. Jha, Andrew Glasgow, Jess Brallier, Katherine Kirkwood, Emilia Bagiella, Dennis S. Charney, James W. Murrough

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Ketamine is an N-methyl-D-aspartate receptor antagonist with rapid antidepressant effects. Studies suggest that inhibition of nitric oxide synthesis plays a role in the mechanism of action of ketamine. This randomized, placebo-controlled study investigated whether co-administration of sodium nitroprusside, a nitric oxide donor, compared to placebo, would attenuate the antidepressant and dissociative effects of ketamine. Sixteen ketamine responders were randomized to a double-blind infusion of ketamine co-administered with placebo or sodium nitroprusside. Our findings show no difference between the two conditions suggesting that the nitric oxide pathway may not play a primary role in ketamine’s antidepressant or dissociative effects. The study is registered at clinicaltrials.gov (NCT03102736).

Original languageEnglish (US)
Pages (from-to)124-127
Number of pages4
JournalJournal of Psychopharmacology
Volume35
Issue number2
DOIs
StatePublished - Feb 2021
Externally publishedYes

Keywords

  • Depression
  • N-methyl-D-aspartate receptor
  • antidepressant
  • dissociation
  • glutamate
  • ketamine
  • nitric oxide
  • sodium nitroprusside

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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