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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
Open accessAbstract
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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“Thirdly, university students who belong to lower class families tend to have more unstable mental states and are more likely to witness depression than middle or upper-class families (61).”
From Family and Academic Stress and Their Impact on Students' Depression Level and Academic Performance (2022) · cites this paper as [61]
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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
- Published
- 2012-02-01
- Volume
- 37
- Issue
- 6
- Pages
- 1526-1533
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- 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
- bronze
- doi.org
- 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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