Lee Sheng-Yu, Wang Tzu-Yun, Chen Shiou-Lan, Chang Yun-Hsuan, Chen Po-See, Huang San-Yuan, Tzeng Nian-Sheng, Wang Liang-Jen, Lee I-Hui, Chen Kao-Ching, Yang Yen-Kuang, Hong Jau-Shyong, Lu Ru-Band
Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Department of Psychiatry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Int J Bipolar Disord. 2020 Mar 2;8(1):11. doi: 10.1186/s40345-019-0174-8.
The aim of this study is to determine whether adding combination of agents with anti-inflammatory and neurotrophic effects is more efficacious than mood stabilizer alone in improving clinical symptoms, plasma brain-derived neurotrophic factor (BDNF), cytokine levels, and metabolic profiles in patients with bipolar spectrum disorder.
In a randomized, double-blind, controlled 12-week clinical trial, patients with moderate mood symptoms (HDRS ≥ 18 or YMRS ≥ 14) were recruited. The patients were randomly assigned to a group while still undergoing regular valproate (VPA) treatments: VPA + dextromethorphan (DM) (30 mg/day) + memantine (MM) (5 mg/day) (DM30 + MM5) (n = 66), VPA + DM (30 mg/day) (DM30) (n = 69), VPA + MM (5 mg/day) (MM5) (n = 66), or VPA + Placebo (Placebo) (n = 69). Symptom severity, immunological parameters [plasma tumor necrosis factor (TNF)-α and C-reactive protein (CRP)] and plasma brain-derived neurotrophic factor (BDNF) were regularly examined. Metabolic profiles [cholesterol, triglycerides, glycosylated hemoglobin (HbA1C), fasting serum glucose, body mass index (BMI)] were measured at baseline and at 2, 8, and 12 weeks.
Depression scores were significantly (P = 0.03) decreases and BDNF levels significantly (P = 0.04) increased in the DM30 + MM5 group than in the Placebo group. However, neither depressive scores nor BDNF levels were significantly different between the DM30, MM5, and Placebo groups. Changes in certain plasma cytokine and BDNF levels were significantly correlated with metabolic parameters.
We concluded that add-on DM30 + MM5 was significantly more effective than placebo for clinical symptoms and plasma BDNF levels. Additional studies with larger samples and mechanistic studies are necessary to confirm our findings. Trial registration NCT03039842 (https://register.clinicaltrials.gov/). Trial date was from 1 Jan 2013 to 31 December 2016 in National Cheng Kung University Hospital. Registered 28 February 1 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03039842?term=NCT03039842&rank=1.
本研究旨在确定添加具有抗炎和神经营养作用的药物组合在改善双相谱系障碍患者的临床症状、血浆脑源性神经营养因子（BDNF）、细胞因子水平及代谢谱方面是否比单独使用心境稳定剂更有效。
在一项随机、双盲、对照的12周临床试验中，招募了具有中度情绪症状（汉密尔顿抑郁量表≥18分或杨氏躁狂量表≥14分）的患者。患者在仍接受常规丙戊酸盐（VPA）治疗的同时被随机分组：VPA + 右美沙芬（DM）（30毫克/天）+ 美金刚（MM）（5毫克/天）（DM30 + MM5）（n = 66），VPA + DM（30毫克/天）（DM30）（n = 69），VPA + MM（5毫克/天）（MM5）（n = 66），或VPA + 安慰剂（安慰剂组）（n = 69）。定期检查症状严重程度、免疫参数[血浆肿瘤坏死因子（TNF）-α和C反应蛋白（CRP）]以及血浆脑源性神经营养因子（BDNF）。在基线以及第2、8和12周测量代谢谱[胆固醇、甘油三酯、糖化血红蛋白（HbA1C）、空腹血清葡萄糖、体重指数（BMI）]。
与安慰剂组相比，DM30 + MM5组的抑郁评分显著降低（P = 0.03），BDNF水平显著升高（P = 0.04）。然而，DM30组、MM5组和安慰剂组之间的抑郁评分和BDNF水平均无显著差异。某些血浆细胞因子和BDNF水平的变化与代谢参数显著相关。
我们得出结论，添加DM30 + MM5在改善临床症状和血浆BDNF水平方面显著优于安慰剂。需要更多样本量的进一步研究和机制研究来证实我们的发现。试验注册号NCT03039842（https://register.clinicaltrials.gov/）。试验日期为2013年1月1日至2016年12月31日，在国立成功大学医院进行。于2017年2月1日追溯注册，https://clinicaltrials.gov/ct2/show/NCT03039842?term=NCT03039842&rank=1。
