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.
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Acknowledgements
We thank Jennifer Vessicchio for her assistance with the preparation of this manuscript. We express our gratitude to all patients who kindly participated in this study. We thank all research assistants, physicians, pharmacists, and nursing staffs at D020 Unit of Taipei Veterans General Hospital for their assistance during the study process, without whom this work could not have been possible. We also very much appreciate Dr Guang Cheng for providing excellent opinions on our work. The study was sponsored by grants from the Ministry of Science and Technology, Taiwan (101-2314-B-010-060, 102-2314-B-010-060) and the Kun-Po Soo Medical Foundation. The participation of Dr Krystal was supported by the US Department of Veterans Affairs via its support for the VA National Center for PTSD, the US National Institute on Alcohol Abuse and Alcoholism (P50AA12870, M01RR00125), and the US National Center for Advancing Translational Science (UL1 RR024139). None of the aforementioned funding organizations had any role in the study design, data collection, analysis, interpretation of result, writing of the report, and the ultimate decision to submit the paper for publication.
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Su, TP., Chen, MH., Li, CT. et al. Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacol. 42, 2482–2492 (2017). https://doi.org/10.1038/npp.2017.94
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DOI: https://doi.org/10.1038/npp.2017.94
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