Antidepressant effects of ketamine in depressed patients
This double-blinded, randomised, placebo-controlled, within-subjects study (n=7) investigated the antidepressant efficacy of a single dose of ketamine (35mg/70kg) in patients with depression and found significant improvements in depressive symptoms within 72 hours after infusion.
Authors
- John Krystal
- Dennis Charney
Published
Abstract
Background
A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-aspartate (NMDA) receptor antagonist in patients with depression.
Methods
Seven subjects with major depression completed 2 test days that involved intravenous treatment with ketamine hydrochloride (.5 mg/kg) or saline solutions under randomized, double-blind conditions.
Results
Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion (i.e., mean 25-item Hamilton Depression Rating Scale scores decreased by 14 6 SD 10 points vs. 0 6 12 points, respectively during active and sham treatment).
Conclusions
These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression.
Research Summary of 'Antidepressant effects of ketamine in depressed patients'
Introduction
A growing body of preclinical research implicates NMDA-class glutamate receptors in the pathophysiology of major depression and in the mechanism of action of antidepressant treatments. Animal studies have shown that NMDA receptor antagonists can produce antidepressant-like effects in many, but not all, paradigms, while chronic administration of conventional antidepressants produces changes in NMDA receptor function and subunit mRNA expression. Early clinical work with agents that modulate NMDA-related sites (for example, amantadine and D-cycloserine) provided some support for this hypothesis but was limited by design and drug-specific issues; overall clinical data on selective NMDA antagonists remain sparse. Berman and colleagues conducted the present study to test whether ketamine hydrochloride, a potent NMDA receptor antagonist, produces antidepressant effects in patients with major depressive episodes. The study aimed to compare a single low-dose intravenous ketamine infusion with saline in a randomised, double-blind, crossover design and to assess mood, depressive symptoms, perceptual effects and safety over the subsequent 72 hours.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 47(4), 351-354. https://doi.org/10.1016/S0006-3223(99)00230-9
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