Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy
Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy
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DOI：
10.1016/s0304-3959(02)00047-7
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发表时间：
2002-07-01
期刊：
影响因子：
7.4
通讯作者：
Johnson, JA
中科院分区：
文献类型：
--
作者：
Hammack, JE;Michalak, JC;Johnson, JA
据报道，三环类抗抑郁药可以缓解与许多病因的周围神经病相关的感觉异常。我们设计了一项随机、双盲、安慰剂对照、交叉试验，以确定去甲替林治疗顺式二氯二氨铂 (CDDP) 引起的感觉异常的疗效。该研究纳入了 51 名患有 CDDP 引起的周围神经病变和疼痛性感觉异常的可评估患者。该研究由两个为期 4 周的阶段组成，中间间隔 1 周的“清除”期，在此期间，患者接受递增剂量的安慰剂或去甲替林。去甲替林的目标最大剂量为 100 毫克/天。每个患者都填写了随机分组前和每周一次的调查问卷，评估 9 周研究中的感觉异常严重程度、睡眠时间、生活质量和不良反应。在第一个治疗期间，去甲替林和安慰剂之间没有观察到感觉异常的显着差异（0-100 分制的平均值分别为 49 和 55，P = 0.78）。尽管在第二个治疗期间观察到了一些有利于去甲替林的适度效果的证据（大约五分之一的患者因药物而使疼痛减轻了 10 点，高于安慰剂效果），但这种情况发生在存在强烈的残留效应的情况下。线性模型分析和贝叶斯方法证实，去甲替林对感觉异常的影响至多是适度的。去甲替林阶段睡眠时间增加（P = 0.02）。去甲替林和安慰剂之间的生活质量测量和感觉异常对患者日常活动的影响没有显着差异。去甲替林没有相关的重大毒性，但去甲替林更常见口干、头晕和便秘。总之，去甲替林未能证明对感觉异常或疼痛有任何作用的有力证据。由于观察到的残留效应，交叉设计第二阶段出现的潜在效应是否存在值得怀疑。结果的交叉验证敏感性分析支持这样的结论：在化疗相关神经病变方面，去甲替林最多比安慰剂提供适度的改善。 (C) 2002 年国际疼痛研究协会。由 Elsevier Science B.V. 出版。保留所有权利。
Tricyclic antidepressants have been reported to relieve the paresthesiae associated with peripheral neuropathies of many etiologies. We designed a randomized, double-blind, placebo-controlled, crossover trial to establish the efficacy of nortriptyline in the treatment of cis-diamminedichloroplatinum (CDDP)-induced paresthesiae. The study included 51 evaluable patients with CDDP-induced peripheral neuropathy and painful paresthesiae. The study consisted of two 4 week phases, separated by a 1 week 'wash-out' period, in which patients received escalating dosages of either placebo or nortriptyline. The target maximum dose of nortriptyline was 100 mg/day. Each patient filled out pre-randomization and then weekly questionnaires assessing paresthesiae severity, hours of sleep, quality of life, and adverse effects over the 9 week study. No significant differences in paresthesia were observed in the first treatment period between nortriptyline and placebo (means of 49 and 55 respectively on a 0-100 point scale, P = 0.78). Although some evidence of a modest effect in favor of nortriptyline was observed during the second treatment period (about one patient in five got a 10-point reduction in pain from drug above placebo effect), this occurred in the presence of a strong carryover effect. Linear models analysis and Bayes methods confirmed that the effect of nortriptyline on paresthesia was modest at best. Hours of sleep increased in the nortriptyline phase (P = 0.02). There was no significant difference in measures of quality of life and the effect of paresthesiae on patients' daily activities between nortriptyline and placebo. There was no major toxicity associated with nortriptyline, but dry mouth, dizziness, and constipation were more common with nortriptyline. In summary, nortriptyline failed to demonstrate strong evidence of any effect on paresthesia or pain. The presence of a potential effect which appeared in the second period of the crossover design is questionable due to the observed carryover effect. Cross-validation sensitivity analysis of results support the conclusion that nortriptyline provides modest improvement at best over placebo in terms of chemotherapy-related neuropathy. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.