A randomized controlled trial of intranasal ketamine in major depressive disorder

Kyle A.B. Lapidus, Cara F. Levitch, Andrew M. Perez, Jess W. Brallier, Michael K. Parides, Laili Soleimani, Adriana Feder, Dan V. Iosifescu, Dennis S. Charney, James W. Murrough

Research output: Contribution to journalArticle

219 Scopus citations

Abstract

Background The N-methyl-D-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial.

Methods In a randomized, double-blind, crossover study, 20 patients with major depression were randomly assigned, and 18 completed 2 treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution. The primary efficacy outcome measure was change in depression severity 24 hours after ketamine or placebo, measured using the Montgomery-Åsberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured.

Results Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo (t = 4.39, p <.001; estimated mean Montgomery-Åsberg Depression Rating Scale score difference of 7.6 ± 3.7; 95% confidence interval, 3.9-11.3). Response criteria were met by 8 of 18 patients (44%) 24 hours after ketamine administration compared with 1 of 18 (6%) after placebo (p =.033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters.

Conclusions This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression.

Original languageEnglish (US)
Pages (from-to)970-976
Number of pages7
JournalBiological Psychiatry
Volume76
Issue number12
DOIs
StatePublished - Dec 15 2014
Externally publishedYes

Keywords

  • Antidepressant
  • depression
  • glutamate
  • intranasal
  • ketamine
  • treatment resistant

ASJC Scopus subject areas

  • Biological Psychiatry

Fingerprint Dive into the research topics of 'A randomized controlled trial of intranasal ketamine in major depressive disorder'. Together they form a unique fingerprint.

  • Cite this

    Lapidus, K. A. B., Levitch, C. F., Perez, A. M., Brallier, J. W., Parides, M. K., Soleimani, L., Feder, A., Iosifescu, D. V., Charney, D. S., & Murrough, J. W. (2014). A randomized controlled trial of intranasal ketamine in major depressive disorder. Biological Psychiatry, 76(12), 970-976. https://doi.org/10.1016/j.biopsych.2014.03.026