Lee Sheng-Yu, Chen Shiou-Lan, Chang Yun-Hsuan, Chen Po See, Huang San-Yuan, Tzeng Nian-Sheng, Wang Yu-Shan, Wang Liang-Jen, Lee I Hui, Wang Tzu-Yun, Yeh Tzung Lieh, Yang Yen Kuang, Hong Jau-Shyong, Lu Ru-Band
From the *Department of Psychiatry, †Institute of Behavioral Medicine, and ‡Institute of Allied Health Sciences, College of Medicine and Hospital, National Cheng Kung University, Tainan; §Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei; ∥Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung; ¶Department of Psychiatry, Tainan Hospital, Department of Health, Executive Yuan, Tainan; #Addiction Research Center, National Cheng Kung University, Tainan, Taiwan; and **Laboratory of Toxicology and Pharmacology, NIH/NIEHS, Research Triangle Park, NC.
J Clin Psychopharmacol. 2014 Jun;34(3):337-43. doi: 10.1097/JCP.0000000000000109.
Memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist with a mood-stabilizing effect, and an association between bipolar disorder and proinflammatory cytokine levels have been reported. Whether adding-on memantine would reduce cytokine levels and is more effective than valproic acid (VPA) alone in bipolar II disorder was investigated. A randomized, double-blind, controlled, 12-week study was conducted. Patients undergoing regular VPA treatments were randomly assigned to a group: VPA + memantine (5 mg/d) (n = 106) or VPA + placebo (n = 108). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response. Symptom severity, plasma tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-8, and IL-1 levels were examined during weeks 0, 1, 2, 4, 8, and 12. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Tumor necrosis factor α levels were significantly lower in the VPA + memantine group than in the VPA + placebo group (P = 0.013). Posttreatment HDRS and YMRS scores decreased significantly in both groups, but not significant, nor was the other between-group cytokine level difference pretreatment and posttreatment. The HDRS score changes were significantly associated with IL-6 (P = 0.012) and IL-1 (P = 0.005) level changes and changes in YMRS score changes with TNF-α (P = 0.005) level changes. Treating bipolar II depression with VPA + memantine may improve the plasma TNF-α level. However, adding-on memantine may not improve clinical symptoms or cytokine levels other than TNF-α. Clinical symptoms may be correlated with certain cytokines.
美金刚是一种具有心境稳定作用的非竞争性N-甲基-D-天冬氨酸受体拮抗剂，且已有报道称双相情感障碍与促炎细胞因子水平之间存在关联。本研究旨在探讨在双相II型障碍中添加美金刚是否会降低细胞因子水平，以及是否比单独使用丙戊酸（VPA）更有效。进行了一项为期12周的随机、双盲、对照研究。接受常规VPA治疗的患者被随机分为两组：VPA + 美金刚（5毫克/天）（n = 106）或VPA + 安慰剂（n = 108）。使用汉密尔顿抑郁量表（HDRS）和杨氏躁狂量表（YMRS）评估临床反应。在第0、1、2、4、8和12周时检查症状严重程度、血浆肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-8和IL-1水平。为了调整重复评估中的受试者内依赖性，使用广义估计方程方法的多元线性回归来检查治疗效果。VPA + 美金刚组的肿瘤坏死因子α水平显著低于VPA + 安慰剂组（P = 0.013）。两组治疗后的HDRS和YMRS评分均显著降低，但无显著性差异，且两组间细胞因子水平在治疗前和治疗后的差异也无显著性。HDRS评分变化与IL-6（P = 0.012）和IL-1（P = 0.005）水平变化显著相关，YMRS评分变化与TNF-α（P = 0.005）水平变化显著相关。用VPA + 美金刚治疗双相II型抑郁症可能会改善血浆TNF-α水平。然而，添加美金刚可能不会改善除TNF-α以外的临床症状或细胞因子水平。临床症状可能与某些细胞因子相关。
