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Cited by 309Treatment of Major DepressionElectroconvulsive Therapy StudiesTryptophan and brain disorders

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Course of Improvement in Depressive Symptoms to a Single Intravenous Infusion of Ketamine vs Add-on Riluzole: Results from a 4-Week, Double-Blind, Placebo-Controlled Study

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Ibrahim, Lobna, DiazGranados, Nancy, Franco-Chaves, Jose, Brutsche, Nancy, Henter, Ioline D, Kronstein, Phillip, Moaddel, Ruin, Wainer, Irving, Luckenbaugh, David A, Manji, Husseini K, Zarate, Carlos A·2012·Neuropsychopharmacology
DOI 10.1038/npp.2011.338PMC PMC3327857
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Abstract

The N-methyl-D-aspartate antagonist ketamine has rapid antidepressant effects in patients with treatment-resistant major depression (TRD); these effects have been reported to last for 1 week in some patients. However, the extent and duration of this antidepressant effect over longer periods has not been well characterized under controlled conditions. Riluzole, a glutamatergic modulator with antidepressant and synaptic plasticity-enhancing effects, could conceivably be used to promote the antidepressant effects of ketamine. This study sought to determine the extent and time course of antidepressant improvement to a single-ketamine infusion over 4 weeks, comparing the addition of riluzole vs placebo after the infusion. Forty-two subjects (18-65) with TRD and a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥ 22 received a single intravenous infusion of ketamine (0.5 mg/kg). Four to six hours post-infusion, subjects were randomized to double-blind treatment with either riluzole (100-200 mg/day; n=21) or placebo (n=21) for 4 weeks. Depressive symptoms were rated daily. A significant improvement (P<0.001) in MADRS scores from baseline was found. The effect size of improvement with ketamine was initially large and remained moderate throughout the 28-day trial. Overall, 27% of ketamine responders had not relapsed by 4 weeks following a single ketamine infusion. The average time to relapse was 13.2 days (SE=2.2). However, the difference between the riluzole and placebo treatment groups was not significant, suggesting that the combination of riluzole with ketamine treatment did not significantly alter the course of antidepressant response to ketamine alone.

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  1. Aitken RC (1969). Measurement of feelings using visual analogue scales. Proc R Soc Med 62: 989–993.
  2. First MB, Spitzer RL, Gibbon M, Williams AR (2001). Structured Clinical Interview for DSM-IV TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P). New York State Psychiatric Institute, Biometrics Research: New York.

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Metadata

Authors
Ibrahim, L., DiazGranados, N., Franco-Chaves, J., Brutsche, N., Henter, I. D., Kronstein, P., Moaddel, R., Wainer, I., Luckenbaugh, D. A., Manji, H. K., & Zarate, C. A.
Affiliations
National Institutes of Health (US)
Corresponding author
Zarate, Carlos A
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2012-02-01
Volume
37
Issue
6
Pages
1526-1533
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2011.338
PMC
PMC3327857
OpenAlex
W2006861654
Cited by
309
References
32
Citations by year
2026: 8 · 2025: 8 · 2024: 13 · 2023: 17 · 2022: 19 · 2021: 16 · 2020: 18 · 2019: 19 · 2018: 19 · 2017: 17 · 2016: 38 · 2015: 37 · 2014: 33 · 2013: 30 · 2012: 14
FWCI
26.82
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
ketamine, riluzole, treatment-resistant depression, major depressive disorder, relapse, NMDA receptor antagonists, glutamatergic modulation, combination therapy
MeSH terms
Adolescent, Adult, Aged, Depression, Double-Blind Method, Female, Follow-Up Studies, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Psychiatric Status Rating Scales, Time Factors, Outcome Assessment, Health Care, Excitatory Amino Acid Antagonists, Riluzole, Young Adult

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