Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L
UCSF Pain Clinical Research Center, University of California, San Francisco 94115, USA.
JAMA. 1998 Dec 2;280(21):1837-42. doi: 10.1001/jama.280.21.1837.
Postherpetic neuralgia (PHN) is a syndrome of often intractable neuropathic pain following herpes zoster (shingles) that eludes effective treatment in many patients.
To determine the efficacy and safety of the anticonvulsant drug gabapentin in reducing PHN pain.
Multicenter, randomized, double-blind, placebo-controlled, parallel design, 8-week trial conducted from August 1996 through July 1997.
Sixteen US outpatient clinical centers.
A total of 229 subjects were randomized.
A 4-week titration period to a maximum dosage of 3600 mg/d of gabapentin or matching placebo. Treatment was maintained for another 4 weeks at the maximum tolerated dose. Concomitant tricyclic antidepressants and/or narcotics were continued if therapy was stabilized prior to study entry and remained constant throughout the study.
The primary efficacy measure was change in the average daily pain score based on an 11-point Likert scale (0, no pain; 10, worst possible pain) from baseline week to the final week of therapy. Secondary measures included average daily sleep scores, Short-Form McGill Pain Questionnaire (SF-MPQ), Subject Global Impression of Change and investigator-rated Clinical Global Impression of Change, Short Form-36 (SF-36) Quality of Life Questionnaire, and Profile of Mood States (POMS). Safety measures included the frequency and severity of adverse events.
One hundred thirteen patients received gabapentin, and 89 (78.8%) completed the study; 116 received placebo, and 95 (81.9%) completed the study. By intent-to-treat analysis, subjects receiving gabapentin had a statistically significant reduction in average daily pain score from 6.3 to 4.2 points compared with a change from 6.5 to 6.0 points in subjects randomized to receive placebo (P<.001). Secondary measures of pain as well as changes in pain and sleep interference showed improvement with gabapentin (P<.001). Many measures within the SF-36 and POMS also significantly favored gabapentin (P< or =.01). Somnolence, dizziness, ataxia, peripheral edema, and infection were all more frequent in the gabapentin group, but withdrawals were comparable in the 2 groups (15 [13.3%] in the gabapentin group vs 11 [9.5%] in the placebo group).
Gabapentin is effective in the treatment of pain and sleep interference associated with PHN. Mood and quality of life also improve with gabapentin therapy.
带状疱疹后神经痛（PHN）是一种带状疱疹（缠腰龙）后常难以治愈的神经性疼痛综合征，许多患者难以得到有效治疗。
确定抗惊厥药物加巴喷丁减轻PHN疼痛的疗效和安全性。
多中心、随机、双盲、安慰剂对照、平行设计，于1996年8月至1997年7月进行的为期8周的试验。
美国16个门诊临床中心。
共229名受试者被随机分组。
为期4周的滴定期，加巴喷丁最大剂量为3600mg/d或匹配的安慰剂。以最大耐受剂量维持治疗4周。如果在研究开始前三环类抗抑郁药和/或麻醉药治疗稳定且在整个研究过程中保持不变，则继续使用。
主要疗效指标是从基线周到治疗最后一周基于11点李克特量表（0，无疼痛；10，可能的最严重疼痛）的平均每日疼痛评分变化。次要指标包括平均每日睡眠评分、简化麦吉尔疼痛问卷（SF-MPQ）、受试者整体变化印象和研究者评定的临床整体变化印象、健康调查简表36（SF-36）生活质量问卷以及情绪状态剖面图（POMS）。安全指标包括不良事件的发生频率和严重程度。
113名患者接受加巴喷丁治疗，其中89名（78.8%）完成研究；116名接受安慰剂治疗，其中95名（81.9%）完成研究。通过意向性分析，接受加巴喷丁治疗的受试者平均每日疼痛评分从6.3分显著降至4.2分，而随机接受安慰剂治疗的受试者从6.5分降至6.0分（P<0.001）。加巴喷丁治疗后，疼痛的次要指标以及疼痛和睡眠干扰的变化均有改善（P<0.001）。SF-36和POMS中的许多指标也显著有利于加巴喷丁（P≤0.01）。加巴喷丁组嗜睡、头晕、共济失调、外周水肿和感染的发生率均更高，但两组的退出率相当（加巴喷丁组为15名[13.3%]，安慰剂组为11名[9.5%]）。
加巴喷丁对治疗与PHN相关的疼痛和睡眠干扰有效。加巴喷丁治疗还可改善情绪和生活质量。
