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.
Key Words
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Article Info
Publication History
Published online: April 04, 2014
Accepted:
March 19,
2014
Received in revised form:
March 16,
2014
Received:
December 10,
2013
Footnotes
Authors DSC and JWM contributed equally to this work.
Identification
Copyright
© 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.