Fernandez Hubert H, Factor Stewart A, Hauser Robert A, Jimenez-Shahed Joohi, Ondo William G, Jarskog L Fredrik, Meltzer Herbert Y, Woods Scott W, Bega Danny, LeDoux Mark S, Shprecher David R, Davis Charles, Davis Mat D, Stamler David, Anderson Karen E
From the Cleveland Clinic (H.H.F.), Center for Neurological Restoration, Cleveland, OH; Emory University (S.A.F.), Atlanta, GA; University of South Florida Parkinson's Disease and Movement Disorders Center (R.A.H.), Tampa, FL; Baylor College of Medicine (J.J.-S.), Houston, TX; Methodist Neurological Institute (W.G.O.), Houston, TX; University of North Carolina School of Medicine (L.F.J.), Chapel Hill, NC; Northwestern University Feinberg School of Medicine (H.Y.M., D.B.), Chicago, IL; Yale School of Medicine (S.W.W.), New Haven, CT; University of Tennessee Health Science Center (M.S.L.), Memphis, TN; University of Utah Health Care (D.R.S.), Salt Lake City, UT; Banner Sun Health Research Institute (D.R.S.), Sun City, AZ; CSD Biostatistics (C.D.), Tucson, AZ; Teva Pharmaceutical Industries (M.D.D.), Frazer, PA; Teva Pharmaceuticals (D.S.), La Jolla, CA; and Georgetown University (K.E.A.), Washington, DC.
Neurology. 2017 May 23;88(21):2003-2010. doi: 10.1212/WNL.0000000000003960. Epub 2017 Apr 26.
To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD).
One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) score of ≥6 assessed by blinded central video rating, stable psychiatric illness, and stable psychoactive medication treatment. Primary endpoint was the change in AIMS score from baseline to week 12. Secondary endpoints included treatment success at week 12 on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change.
For the primary endpoint, deutetrabenazine significantly reduced AIMS scores from baseline to week 12 vs placebo (least-squares mean [standard error] -3.0 [0.45] vs -1.6 [0.46], = 0.019). Treatment success on CGIC (48.2% vs 40.4%) favored deutetrabenazine but was not significant. Deutetrabenazine and placebo groups showed low rates of psychiatric adverse events: anxiety (3.4% vs 6.8%), depressed mood/depression (1.7% vs 1.7%), and suicidal ideation (0% vs 1.7%, respectively). In addition, no worsening in parkinsonism, as measured by the Unified Parkinson's Disease Rating Scale motor subscale, was noted from baseline to week 12 in either group.
In patients with TD, deutetrabenazine was well tolerated and significantly reduced abnormal movements.
This study provides Class I evidence that in patients with TD, deutetrabenazine reduces AIMS scores.
确定氘代丁苯那嗪治疗迟发性运动障碍（TD）的疗效和安全性。
在这项随机、双盲、多中心试验中，117例中重度TD患者接受了氘代丁苯那嗪或安慰剂治疗。入选标准包括由盲态的中央视频评分评估的异常不自主运动量表（AIMS）得分≥6、稳定的精神疾病以及稳定的精神活性药物治疗。主要终点是从基线到第12周AIMS得分的变化。次要终点包括第12周时基于临床总体印象变化量表（CGIC）和患者总体印象变化量表的治疗成功情况。
对于主要终点，与安慰剂相比，氘代丁苯那嗪从基线到第12周显著降低了AIMS得分（最小二乘均值[标准误]-3.0[0.45]对-1.6[0.46]，P=0.019）。CGIC上的治疗成功情况（48.2%对40.4%）有利于氘代丁苯那嗪，但无显著差异。氘代丁苯那嗪组和安慰剂组的精神科不良事件发生率较低：焦虑（3.4%对6.8%）、情绪低落/抑郁（1.7%对1.7%）以及自杀观念（分别为0%对1.7%）。此外，两组从基线到第12周，由统一帕金森病评定量表运动子量表测量的帕金森综合征均未恶化。
在TD患者中，氘代丁苯那嗪耐受性良好，且能显著减少异常运动。
本研究提供了I类证据，表明在TD患者中，氘代丁苯那嗪可降低AIMS得分。
