Hammack Julie E, Michalak John C, Loprinzi Charles L, Sloan Jeff A, Novotny Paul J, Soori Gamini S, Tirona Maria Tria, Rowland Kendrith M, Stella Philip J, Johnson Joanne A
Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Pain. 2002 Jul;98(1-2):195-203. doi: 10.1016/s0304-3959(02)00047-7.
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.
据报道，三环类抗抑郁药可缓解多种病因所致周围神经病变相关的感觉异常。我们设计了一项随机、双盲、安慰剂对照的交叉试验，以确定去甲替林治疗顺铂（CDDP）所致感觉异常的疗效。该研究纳入了51例可评估的CDDP诱导的周围神经病变和疼痛性感觉异常患者。该研究包括两个为期4周的阶段，中间间隔1周的“洗脱期”，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100mg/天。每位患者在随机分组前以及在为期9周的研究中每周填写问卷，评估感觉异常的严重程度、睡眠时间、生活质量和不良反应。在第一个治疗期，去甲替林和安慰剂之间在感觉异常方面未观察到显著差异（在0-100分的量表上，平均分分别为49分和55分，P=0.78）。虽然在第二个治疗期观察到一些有利于去甲替林的适度效果的证据（约五分之一的患者因药物作用疼痛较安慰剂组减轻10分），但这是在存在强烈的残留效应的情况下发生的。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充其量是适度的。去甲替林治疗阶段睡眠时间增加（P=0.02）。去甲替林和安慰剂在生活质量测量以及感觉异常对患者日常活动的影响方面没有显著差异。去甲替林没有相关的重大毒性，但口干、头晕和便秘在去甲替林组更常见。总之，去甲替林未能证明对感觉异常或疼痛有任何显著效果。由于观察到的残留效应，交叉设计第二个阶段出现的潜在效果值得怀疑。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，去甲替林相比安慰剂充其量只提供了适度的改善。
