Movement Disorders Clinic,Schools of Medicine and Pharmacy, Loma Linda University, 11262 Campus Street, Loma Linda, CA 92350, USA.
Clin Ther. 2012 Jul;34(7):1487-504. doi: 10.1016/j.clinthera.2012.06.010. Epub 2012 Jun 28.
Tetrabenazine (TBZ) is a monoamine storage inhibitor that was first introduced in the 1970s for the management of hyperkinetic movement disorders. Despite acceptance and usage worldwide, TBZ was only recently approved in the United States for the treatment of Huntington chorea. This review focuses on the use of TBZ in various hyperkinetic movement disorders, which are considered "rare" or "orphan" diseases, to help practitioners better understand its clinical role and use.
This review describes the clinical efficacy and tolerability of TBZ in the management of dystonia, Huntington chorea, tardive dyskinesia (TDk), and tic disorders.
A Cochrane Library, EMBASE, MedlinePlus, PubMed, and clinical trials database search (up to May 2012) was conducted to identify articles and studies using the subject terms tetrabenazine, Huntington disease, dystonia, tardive dyskinesia, Tourette, tics, and hyperkinetic movement. Only English-language articles were reviewed.
TBZ variably undergoes extensive first-pass metabolism to active metabolites, some of which are metabolized by the cytochrome P450 2D6 isozyme. Pharmacology studies demonstrate that TBZ reversibly inhibits the activity of vesicular monoamine transporter 2, resulting in depletion of central dopamine. For management of dystonias, 1 of 3 small prospective blinded studies and 4 of 5 retrospective studies reported clinical benefit with TBZ use in pediatrics and adults. For Huntington chorea, 2 randomized, double-blind, placebo-controlled studies along with open-label studies demonstrate the effectiveness of TBZ in adults. For TDk, 9 of 11 studies (prospective controlled and retrospective) reported positive benefit. For Gilles de la Tourette syndrome, 9 of 11 studies (prospective controlled and retrospective) reported positive benefit on motor and phonic tics in pediatric and adult patients. Overall, adverse effects are dose and age related and include depression, fatigue, parkinsonism, and somnolence.
TBZ is an effective oral therapy for chorea of Huntington disease and may be considered as an alternative agent for the management of dystonia, TDk, and tic disorders (these latter 3 conditions are off-label uses in the United States). The drug possesses an acceptable tolerability profile and has been used in pediatric and adult populations.
四苯丁嗪（TBZ）是一种单胺储存抑制剂，于 20 世纪 70 年代首次用于治疗多动性运动障碍。尽管在全球范围内得到认可和应用，但 TBZ 直到最近才被美国批准用于亨廷顿舞蹈症的治疗。本综述重点介绍了 TBZ 在各种多动性运动障碍中的应用，这些障碍被认为是“罕见”或“孤儿”疾病，以帮助从业者更好地了解其临床作用和用途。
本综述描述了 TBZ 在治疗肌张力障碍、亨廷顿舞蹈症、迟发性运动障碍（TDk）和抽动障碍中的临床疗效和耐受性。
对 Cochrane 图书馆、EMBASE、MedlinePlus、PubMed 和临床试验数据库（截至 2012 年 5 月）进行了检索，以确定使用主题词四苯丁嗪、亨廷顿病、肌张力障碍、迟发性运动障碍、图雷特综合征、抽动和多动性运动的文章和研究。仅对英语文章进行了综述。
TBZ 广泛经历首过代谢转化为活性代谢物，其中一些代谢物由细胞色素 P450 2D6 同工酶代谢。药理学研究表明，TBZ 可逆地抑制囊泡单胺转运体 2 的活性，导致中枢多巴胺耗竭。对于肌张力障碍的治疗，3 项小型前瞻性盲法研究中的 1 项和 5 项回顾性研究中的 4 项报告了 TBZ 治疗儿科和成人患者的临床获益。对于亨廷顿舞蹈症，2 项随机、双盲、安慰剂对照研究以及开放标签研究表明 TBZ 对成人有效。对于迟发性运动障碍，11 项研究中的 9 项（前瞻性对照和回顾性）报告了阳性获益。对于 Gilles de la Tourette 综合征，11 项研究中的 9 项（前瞻性对照和回顾性）报告了儿科和成年患者运动性和发音性抽动的阳性获益。总体而言，不良反应与剂量和年龄有关，包括抑郁、疲劳、帕金森病和嗜睡。
TBZ 是亨廷顿舞蹈症舞蹈症的有效口服治疗药物，可考虑作为肌张力障碍、TDk 和抽动障碍（这些疾病在美国是超适应证使用）管理的替代药物。该药物具有可接受的耐受性，已在儿科和成人人群中使用。
