Meyer Jonathan M
1Department of Psyshiatry,University of California,San Diego,California,USA.
CNS Spectr. 2016 Dec;21(S1):13-24. doi: 10.1017/S1092852916000730.
The broad use of atypical antipsychotics was expected to dramatically reduce the prevalence and incidence of tardive dyskinesia (TD), but data show that TD remains an important challenge due the persistent nature of its symptoms and resistance to numerous treatment modalities, including antipsychotic discontinuation. Recent insights on genetic risk factors and new concepts surrounding pathophysiology have spurred interest in the possibility of targeted treatment for TD. As will be reviewed in this article, the number of evidence-based strategies for TD treatment is small: only clonazepam, amantadine, ginkgo biloba extract, and the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine have compelling data. Using new insights into the metabolism of tetrabenazine and the properties of its active metabolites, 2 modifications of tetrabenazine have been synthesized to improve the kinetic profile, and are currently involved in double-blind placebo controlled studies aimed at U.S. Food and Drug Administration (FDA) regulatory approval. The possible availability of these new agents, deuterated tetrabenazine and valbenazine, significantly widens the range of treatment choices for patients with TD. For clinicians with patients at risk for TD due to dopamine antagonist exposure, experience has shown that the problem of TD will be an ongoing issue in modern psychiatry, and that an appreciation of new developments in the pathophysiology of, risk factors for, and treatment of TD is crucial to managing this condition.
非典型抗精神病药物的广泛使用原本有望大幅降低迟发性运动障碍（TD）的患病率和发病率，但数据显示，由于其症状的持续性以及对包括停用抗精神病药物在内的多种治疗方式具有抗性，TD仍然是一项重大挑战。近期对遗传风险因素的认识以及围绕病理生理学的新概念激发了人们对TD靶向治疗可能性的兴趣。正如本文将要阐述的，TD治疗的循证策略数量较少：仅有氯硝西泮、金刚烷胺、银杏叶提取物以及囊泡单胺转运体2（VMAT2）抑制剂丁苯那嗪有令人信服的数据。利用对丁苯那嗪代谢及其活性代谢物特性的新认识，已合成了丁苯那嗪的2种改良型以改善动力学特征，目前正参与旨在获得美国食品药品监督管理局（FDA）监管批准的双盲安慰剂对照研究。这些新药物，氘代丁苯那嗪和缬苯那嗪，可能的可用性显著拓宽了TD患者的治疗选择范围。对于因接触多巴胺拮抗剂而使患者有患TD风险的临床医生而言，经验表明，TD问题在现代精神病学中仍将是一个持续存在的问题，了解TD病理生理学、风险因素及治疗方面的新进展对于管理这种病症至关重要。
