Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression
This double-blind, randomised, parallel-group, placebo-controlled trial study (n=71) examines adjunctive ketamine's dose-related effects in Taiwanese patients with treatment-resistant depression (TRD). This first such report showing the dose-related efficacy of ketamine for TRD, and characterized ketamine effects in a genotyped Chinese group in which 83% of patients had at least one copy of the BDNF gene's lower functioning Met allele.
Authors
- John Krystal
- Tung-Ping Su
- Mu-Hong Chen
Published
Abstract
The antidepressant effects of ketamine are thought to depend on brain-derived neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to characterize the dose-related antidepressant effects of ketamine in patients with treatment-resistant depression drawn from a Chinese population predominately possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a double-blind, randomized, parallel-group, placebo-controlled trial of a single ketamine infusion (saline, 0.2 mg/kg, 0.5 mg/kg). Patients (N=71; BDNF genotype: Val/Val (N=12, 17%), Val/Met (N=40, 56.3%), and Met/Met (N=19, 26.8%)) received mood ratings before infusion, after infusion, and for the subsequent 14 days. Plasma ketamine levels and BDNF genotypes were assessed. This study found a significant dose-related ketamine effect on scores on the Hamilton Depression Rating Scale (HAMD). The responder analysis (>50% reduction from baseline HAMD on at least 2 days between days 2 and 5) also revealed a significant dose-related effect (saline: 12.5%, 0.2 mg/kg: 39.1%; 0.5 mg/kg: 45.8%). This is the first report to our knowledge to demonstrate the dose-related efficacy of R/S-ketamine for treatment-resistant depression and the first to characterize ketamine effects in a genotyped Chinese population in which most (83%) patients possessed at least one copy of the lower functioning Met allele of the BDNF gene.
Research Summary of 'Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression'
Introduction
Ketamine has been shown in prior research to produce rapid antidepressant effects in patients with treatment-resistant depression, in contrast to the slow onset and modest remission rates associated with standard antidepressants. Despite replicated signals of efficacy, important practical questions remain unresolved, notably the dose–response relationship for R/S-ketamine when used as a 40 minute intravenous infusion and the generalisability of findings across racial and ethnic groups. There is particular interest in Han Chinese and Taiwanese populations because of a high prevalence of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene, in which the Met allele has been suggested by some preclinical and small clinical studies to attenuate ketamine’s antidepressant response. Su and colleagues therefore set out to characterise the dose-related antidepressant effects of adjunctive R/S-ketamine in Taiwanese patients with treatment-resistant major depressive disorder who were genotyped for the BDNF Val66Met polymorphism. The trial tested single infusions of saline (placebo), 0.2 mg/kg, and 0.5 mg/kg R/S-ketamine, with serial mood ratings and plasma pharmacokinetics, to determine whether antidepressant effects vary by dose, baseline depression severity, and BDNF genotype.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Su, T., Chen, M., Li, C., Lin, W., Hong, C., Gueorguieva, R., Tu, P., Bai, Y., Cheng, C., & Krystal, J. H. (2017). Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacology, 42(13), 2482-2492. https://doi.org/10.1038/npp.2017.94
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Zhang, J. C., Yao, W., Hashimoto, K. · Neuropharmacology (2022)
Price, R., Kissel, N., Baumeister, A. et al. · Molecular Psychiatry (2022)
Medeiros, G. C., Gould, T. D., Prueitt, W. L. et al. · Molecular Psychiatry (2022)
Gallagher, B., Foley, M., Slattery, C. M. et al. · HRB Open Research (2022)
Abdallah, C. G., Roache, J. D., Gueorguieva, R. et al. · Neuropsychopharmacology (2022)
Meshkat, S., Rodrigues, N. B., Vincenzo, J. D. D. et al. · Journal of Psychiatric Research (2022)
de Mendoça Lima, T., Visacri, M. B., Aguiar, P. M. · European Journal of Clinical Pharmacology (2021)
Conley, A. A., Norwood, A. E. Q., Hatvany, T. C. et al. · Psychopharmacology (2021)
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Shiroma, P. R., Thuras, P., Wels, J. et al. · Translational Psychiatry (2020)
Hashimoto, K. · Psychiatry and Clinical Neurosciences (2019)
Abdallah, C. G., Charney, D. S., Duman, R. S. et al. · Neuron (2019)
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