Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Beitou district, Taipei, 112, Taiwan.
Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Eur Arch Psychiatry Clin Neurosci. 2021 Oct;271(7):1267-1274. doi: 10.1007/s00406-021-01264-w. Epub 2021 May 7.
Evidence suggests that levels of treatment refractoriness and brain-derived neurotrophic factor (BDNF) rs6265 polymorphism are related to the antidepressant effects of conventional antidepressants and repetitive transcranial magnetic stimulation. However, whether these factors are associated with the antidepressant effects of low-dose ketamine remains unclear. In total, 71 patients with treatment-resistant depression (TRD) were randomized to 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline control infusion groups. They were further divided into three treatment refractoriness groups according to the Maudsley staging method and were genotyped for Val66Met BDNF polymorphism. Participants' Hamilton Depression Rating Scale (HDRS) scores were assessed preinfusion, at 40, 80, 120, and 240 min postinfusion, and sequentially on days 2-7 and 14 after infusion. Patients with any Val allele exhibited an antidepressant response (p = 0.029) to 0.5 mg/kg ketamine vs. 0.2 mg/kg ketamine vs. saline control infusions. However, the trajectory of HDRS scores did not differ (p = 0.236) between the treatment groups among Met/Met carriers. In the low treatment refractoriness group, the 0.2 mg/kg ketamine infusion exhibited the optimal antidepressant effect (p = 0.002); in the moderate treatment refractoriness group, the 0.5 mg/kg ketamine infusion achieved the strongest antidepressant effect (p = 0.006); however, in the high treatment refractoriness group, the trajectory of depressive symptoms did not differ between treatments (p = 0.325). In future clinical practice, ketamine dose may be adjusted according to the level of treatment refractoriness and BDNF rs6265 polymorphism to achieve the optimal antidepressant effect for patients with TRD.
有证据表明，治疗抵抗水平和脑源性神经营养因子（BDNF）rs6265 多态性与传统抗抑郁药和重复经颅磁刺激的抗抑郁作用有关。然而，这些因素是否与低剂量氯胺酮的抗抑郁作用有关尚不清楚。共有 71 例治疗抵抗性抑郁症（TRD）患者被随机分为 0.5mg/kg 氯胺酮、0.2mg/kg 氯胺酮和生理盐水对照组。根据莫兹利分期法，他们进一步分为三组治疗抵抗组，并对 Val66Met BDNF 多态性进行基因分型。参与者的汉密尔顿抑郁评定量表（HDRS）评分在输注前、输注后 40、80、120 和 240 分钟以及输注后第 2-7 天和第 14 天进行评估。任何 Val 等位基因的患者对 0.5mg/kg 氯胺酮（p=0.029）比 0.2mg/kg 氯胺酮（p=0.029）比生理盐水对照组的抗抑郁反应。然而，在 Val/Met 携带者中，各组间 HDRS 评分的轨迹没有差异（p=0.236）。在低治疗抵抗组中，0.2mg/kg 氯胺酮输注显示出最佳的抗抑郁作用（p=0.002）；在中度治疗抵抗组中，0.5mg/kg 氯胺酮输注显示出最强的抗抑郁作用（p=0.006）；然而，在高治疗抵抗组中，治疗之间的抑郁症状轨迹没有差异（p=0.325）。在未来的临床实践中，根据治疗抵抗水平和 BDNF rs6265 多态性调整氯胺酮剂量，可能会为 TRD 患者实现最佳的抗抑郁效果。
