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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

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


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.

[Available on 2018-12-01]
[Indexed for MEDLINE]

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