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
Pages (from-to)124-127
Number of pages4
JournalJournal of Psychopharmacology
Issue number2
StatePublished - Feb 2021


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


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