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Neuropsychopharmacology. 2017 Dec;42(13):2482-2492. doi: 10.1038/npp.2017.94. Epub 2017 May 11.

Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression.

Su TP1,2,3,4, Chen MH2,4, Li CT1,2,4, Lin WC2,4, Hong CJ1,2,4, Gueorguieva R5,6, Tu PC1,2,3, Bai YM1,2, Cheng CM2, Krystal JH6,7,8,9.

Author information

1
Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
2
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
3
Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
4
Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
5
Department of Biostatistics, School of Public Health, Yale University, New Haven, CT, USA.
6
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
7
Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
8
Yale-New Haven Hospital, New Haven, CT, USA.
9
VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA.

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.

PMID:
28492279
PMCID:
PMC5686503
[Available on 2018-12-01]
DOI:
10.1038/npp.2017.94
[Indexed for MEDLINE]

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