Amitriptyline in Neuropathic Cancer Pain in Patients on Morphine Therapy: A Randomized Placebo-controlled, Double-blind Crossover Study
Amitriptyline in Neuropathic Cancer Pain in Patients on Morphine Therapy: A Randomized Placebo-controlled, Double-blind Crossover Study
复制标题
阿米替林治疗吗啡治疗患者的神经性癌痛：一项随机安慰剂对照、双盲交叉研究
作者：
S. Mercadante;E. Arcuri;W. Tirelli;P. Villari;A. Casuccio
目的和背景阿米替林是最常见的镇痛辅助用于癌症患者的神经性疼痛，即使没有具体的研究已经证明了一个好处。一项随机安慰剂对照、双盲交叉研究旨在证明阿米替林对神经性癌痛患者的作用。方法选择16例晚期癌症患者，均为神经病理性疼痛，接受全身吗啡治疗，不再接受肿瘤治疗，过去1周内出现中度疼痛（疼痛程度≥ 4，但小于7，评分范围0-10），过去2天内给予稳定剂量的吗啡。在研究的第一周期间，患者在夜间给予25 mg阿米替林或等效的安慰剂滴剂，持续3天，并在随后的4天给予50 mg。65岁以上患者的剂量为15 mg（前3天）和30 mg（后3天）。一周后，第二周进行交叉，另一种治疗顺序相反。记录研究开始前、研究开始后第一周和研究开始后第二周的阿片类药物消耗、疼痛强度、症状和不良反应、情绪、睡眠、患者偏好、生活质量。结果阿米替林与安慰剂相比，在治疗前一周的整体疼痛强度、最小疼痛强度或治疗一周后的疼痛评估中，在访视时没有发现镇痛的显著益处。两组最严重疼痛程度差异有统计学意义（P < 0.035）。阿米替林组的嗜睡、意识模糊和口干症状明显比安慰剂组严重（分别为P < 0.036、0.003和0.034）。两种治疗在Spitzer生活质量评分和每个项目上没有实质性差异。阿米替林的镇痛作用轻微，且伴有不良反应。结论根据本研究的结果，该药在癌痛中的广泛应用值得商榷。
Aims and Background Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain, even though no specific studies have demonstrated a benefit. A randomized placebo-controlled, double-blind crossover study was designed to evidence the effects of amitriptyline in patients with neuropathic cancer pain. Methods Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy, no longer receiving oncologic treatment, presenting moderate pain (about 4 or more, but less than 7, on a numerical scale of 0-10) in the last week, and given a stable morphine dose in the last 2 days were admitted to the study. During the first week of study, patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days. Doses for patients aged more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a week, a crossover took place for the second week, with the other treatment at an inverse sequence. Opioid consumption, pain intensity, symptoms and adverse effects, mood, sleep, patient's preference, quality of life before starting the study, the first week after and the second week after were recorded. Results No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment, the least pain intensity or the pain evaluated just after a week of treatment, at the moment of the visit, when amitriptyline was compared with placebo. A significant difference was evidenced for the worst pain (P < 0.035). No differences in opioid doses during the period of study were found. Drowsiness, confusion and dry mouth were significantly more intense with amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively). There were no substantial differences between the two treatments in Spitzer's quality of life score and for each item. No differences in patients' preference for the two treatment periods were found. The analgesic effects of amitriptyline were slight and associated with adverse effects. Conclusions In light of the results obtained in the study, the extensive use of the drug for cancer pain should be questioned.