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迟发性运动障碍的临床诊治进展

王喜喜 万新华

王喜喜, 万新华. 迟发性运动障碍的临床诊治进展[J]. 协和医学杂志, 2022, 13(4): 644-651. doi: 10.12290/xhyxzz.2021-0717
引用本文: 王喜喜, 万新华. 迟发性运动障碍的临床诊治进展[J]. 协和医学杂志, 2022, 13(4): 644-651. doi: 10.12290/xhyxzz.2021-0717
WANG Xixi, WAN Xinhua. Clinical Diagnosis and Treatment of Tardive Dyskinesia[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(4): 644-651. doi: 10.12290/xhyxzz.2021-0717
Citation: WANG Xixi, WAN Xinhua. Clinical Diagnosis and Treatment of Tardive Dyskinesia[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(4): 644-651. doi: 10.12290/xhyxzz.2021-0717

迟发性运动障碍的临床诊治进展

doi: 10.12290/xhyxzz.2021-0717
基金项目: 

国家自然科学基金 81971074

详细信息
    通讯作者:

    万新华, E-mail: wxhpumch@163.com

  • 中图分类号: R746; R741.02

Clinical Diagnosis and Treatment of Tardive Dyskinesia

Funds: 

National Natural Science Foundation of China 81971074

More Information
  • 摘要: 迟发性运动障碍(tardive dyskinesia,TD)是与长期服用多巴胺受体阻滞剂相关的一种异常不自主运动,可累及面颈部,引起伸舌、咀嚼、噘嘴、歪颌或转颈,也可累及四肢和躯干,表现为舞蹈样动作。临床上最常见的病因为抗精神病药物(antipsychotic drug,APD)的使用。与TD相关的危险因素包括APD的种类、用药剂量和时间、年龄和性别,遗传因素也发挥一定作用。目前研究较多的TD相关基因为CYP2D6、DRD2、DRD3、HTR2A、HTR2C、VMAT2、MnSOD、HSPG2。TD的发病机制尚不明确,主要有多巴胺受体超敏学说、氧化应激学说和突触可塑性失调学说。临床上治疗TD较为困难,预防至关重要。本文就TD的临床诊治进展进行综述,以进一步加深医务人员对该疾病的认识。
    作者贡献:王喜喜负责查阅文献、撰写论文;万新华负责修订、审校论文。
    利益冲突:所有作者均声明不存在利益冲突
  • 表  1  CYP2D6基因与TD相关的变异[23]

    基因 核苷酸突变 蛋白质变异 功能
    rs16947 2851C>T R296C 正常(野生型)
    rs1135840 4181G>C S486T 正常
    rs5030656 2616delAAG K281缺失 下降
    rs1065852 100C>T P34S 下降
    rs28371706 1022C>T T107I 下降
    rs28371725 2851C>T R296C 下降
    rs35742686 2550delA 259移码
    rs3892097 1847G>A 剪接/169移码
    rs5030655 1708delT 152移码
    TD: 迟发性运动障碍
    下载: 导出CSV

    表  2  编码多巴胺受体的候选基因作为TD风险预测因子的相关研究[24]

    基因 编码蛋白 位置 变异 是否与TD风险相关 样本来源
    DRD1 多巴胺D1受体 5q35.2 rs4532(A/G) 亚洲
    DRD2 多巴胺D2受体 11q23.2 rs6277(C/T) 荷兰和比利时
    rs6275(C/T) 荷兰和比利时
    -
    rs1800497(C/T) TaqIA多态性(是) 美国
    -
    rs1079597(A/G) TaqIB多态性(是) 美国
    rs1799732(141CIns/Del) 日本
    荷兰和比利时
    rs1800498(T/C) -
    rs1801028(C/G) -
    rs1045280(C/T) 中国
    DRD3 多巴胺D3受体 3q13.31 rs6280(C/T) 中国
    rs905568(C/G) 美国
    rs9817063(T/C) -
    rs2134655(G/A) - -
    rs963468(G/A) - -
    rs324035(C/A) - -
    rs3773678(C/T) - -
    rs167771(A/G) - -
    rs11721264(G/A) - -
    rs167770(A/G) - -
    rs9633291(T/G) - -
    rs1800828(G/C) - -
    DRD4 多巴胺D4受体 11p15.5 rs3758653(T/C) - -
    rs1800955(T/C) - -
    TD: 同表 1;-:缺少相关数据
    下载: 导出CSV

    表  3  关于TD患者的全基因组关联分析研究[24]

    年份(年) 基因 样本来源
    2008 SLC6A11,GABRB2,GABRG3 日本
    2010 ZNF202 美国
    2011 HSPG2 日本
    2021 FOXP1 俄罗斯
    2021 TNFRSF1B,EPB41L2,CALCOCO1 东亚、欧洲和非洲裔美国人
    TD: 同表 1
    下载: 导出CSV

    表  4  三种VMAT2抑制剂比较[49-50]

    VMAT2抑制剂 起始剂量(mg) 最大剂量(mg) 半衰期(h) 给药频率 不良反应
    丁苯那嗪(TBZ) 12.5 150 5~7 3次/d 直立性低血压、胃肠运动障碍、鼻塞、抑郁、锥体外系不良反应
    氘丁苯那嗪(DBZ) 12 48 9~10 2次/d 头痛、嗜睡、帕金森病
    缬苯那嗪(VBZ) 40 80 15~22 1次/d 头痛、嗜睡、静坐不能、口干
    VMAT2:囊泡单胺转运体2
    下载: 导出CSV

    表  5  TD治疗方案推荐[47, 59-60]

    治疗方法(最大日剂量) 作用机制 不良反应 证据级别
    典型APD转为非典型APD 低D2受体亲和力 - -
    氯硝西泮(4.5 mg) GABA能(GABAA受体) 镇静、共济失调、跌倒风险 B级
    金刚烷胺(400 mg) NMDA受体拮抗剂 失眠、便秘、头晕、认知损害 C级
    银杏叶提取物(240 mg) 抗氧化剂 - B级
    维生素E(1600 IU)
    维生素B6(1200 mg)
    TBZ(150 mg) VMAT2抑制剂 直立性低血压、胃肠运动障碍、鼻塞、抑郁 B级
    DBZ(48 mg) 头痛、嗜睡、帕金森病 A级
    VBZ(80 mg) 头痛、嗜睡、静坐不能、口干 A级
    BTX 阻断神经肌肉接头乙酰胆碱释放 注射部位肌无力 -
    GPi-DBS 刺激苍白球深部 平衡障碍 C级
    TD:同表 1;APD:抗精神病药物;TBZ:丁苯那嗪;DBZ:氘丁苯那嗪;VBZ:缬苯那嗪;BTX:肉毒毒素;GPi-DBS:苍白球内深部脑刺激;-:同表 2;VMAT2:同表 4
    下载: 导出CSV
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出版历程
  • 收稿日期:  2021-10-29
  • 录用日期:  2021-11-22
  • 网络出版日期:  2022-01-30
  • 刊出日期:  2022-07-30

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