Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
Neuropsychopharmacology. 2017 Dec;42(13):2482-2492. doi: 10.1038/npp.2017.94. Epub 2017 May 11.
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.
氯胺酮的抗抑郁作用被认为取决于脑源性神经营养因子（BDNF）基因型和剂量。本研究的目的是描述在中国人群中，以具有较低活性 BDNF 基因型（Val/Met、Met/Met）为主的难治性抑郁症患者中，氯胺酮剂量相关的抗抑郁作用。我们进行了一项双盲、随机、平行组、安慰剂对照试验，单次氯胺酮输注（生理盐水、0.2mg/kg、0.5mg/kg）。患者（N=71；BDNF 基因型：Val/Val（N=12，17%）、Val/Met（N=40，56.3%）和 Met/Met（N=19，26.8%））在输注前、输注后和随后的 14 天内进行情绪评分。评估血浆氯胺酮水平和 BDNF 基因型。本研究发现，氯胺酮剂量与汉密尔顿抑郁评定量表（HAMD）评分之间存在显著的剂量相关效应。应答分析（在第 2 天至第 5 天之间至少 2 天内 HAMD 较基线减少≥50%）也显示出显著的剂量相关效应（生理盐水：12.5%；0.2mg/kg：39.1%；0.5mg/kg：45.8%）。这是我们所知的首次报道氯胺酮对难治性抑郁症的剂量相关疗效，也是首次对中国人群进行的基因分型研究，其中大多数（83%）患者至少携带一个较低功能的 BDNF 基因 Met 等位基因。
