Breuer Brenda, Pappagallo Marco, Knotkova Helena, Guleyupoglu Nilufer, Wallenstein Sylvan, Portenoy Russell K
Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, New York 1003, USA.
Clin Ther. 2007 Sep;29(9):2022-30. doi: 10.1016/j.clinthera.2007.09.023.
Approximately 30% of patients with multiple sclerosis (MS) have central pain (CP). The anticonvulsant lamotrigine has been shown to be efficacious in some types of CP, but its efficacy in MS-related CP has not been confirmed.
The aim of this pilot trial was to provide preliminary data for a planned larger trial.
A randomized, double-blind, placebo-controlled, 2-period, crossover pilot study was conducted in a sample of patients aged > or =18 years with CP due to MS. The 2 treatment periods began with an 8-week, double-blind titration period, during which the number of pills of study drug was increased until either total pain relief was achieved, 1 or more unmanageable adverse events were reported, or a maximum of 16 pills (400 mg of lamotrigine) were used daily. A 3-week maintenance period at the final prescribed amount was followed by a 2-week tapering period; there was a 2-week washout between the 2 treatment periods, after which patients were administered the alternate drug. Outcomes before, during, and after each study period were assessed using validated measures of pain and quality of life (the Brief Pain Inventory [BH], the Neuropathic Pain Scale [NPS], and the 54-item MS Quality of Life [MSQOL-54] questionnaire). Throughout the trial, patients completed a daily diary consisting of questions from the BPI-Short Form, as well as questions about the use of other analgesic drugs, changes in health, and the occurrence of adverse events. The BPI and NPS were completed weekly during telephone calls with the research coordinator, and the MSQOL-54 was administered during clinic visits (ie, visits at screening, baseline, end of period 1, and termination). The primary outcome measure was the mean pain intensity score during the final maintenance week of each of the 2 study periods.
A total of 12 patients were enrolled and completed at least the first period of the study. Ten patients were women. The mean (SD) age was 49.3 (11.7) years, and the mean (SD) weight was 76.5 (19.9) kg. The analysis revealed no significant differences between the lamotrigine and placebo periods in any of the study outcomes related to pain or quality of life. Regarding adverse events, 1 patient developed a moderate rash during the study, but the physician attributed this lesion to herpes zoster; this patient completed the study. While other adverse events were mild, 2 patients were withdrawn from the study after experiencing adverse events during the first study period; 1 had been receiving lamotrigine and the other placebo.
The results from this pilot trial did not support either the use of lamotrigine in patients with MS-related CP or the need for a larger trial.
约30%的多发性硬化症（MS）患者患有中枢性疼痛（CP）。抗惊厥药物拉莫三嗪已被证明对某些类型的CP有效，但其对MS相关性CP的疗效尚未得到证实。
本试点试验的目的是为计划中的更大规模试验提供初步数据。
对年龄≥18岁的MS相关性CP患者样本进行了一项随机、双盲、安慰剂对照、两阶段交叉试点研究。两个治疗阶段始于为期8周的双盲滴定期，在此期间，研究药物的药丸数量逐渐增加，直至实现完全疼痛缓解、报告1种或更多难以处理的不良事件，或每日最多使用16粒药丸（400mg拉莫三嗪）。在最终规定剂量下进行3周的维持期，随后是2周的减量期；两个治疗阶段之间有2周的洗脱期，之后患者服用另一种药物。使用经过验证的疼痛和生活质量测量方法（简明疼痛量表[BPI]、神经病理性疼痛量表[NPS]和54项MS生活质量[MSQOL-54]问卷）评估每个研究阶段之前、期间和之后的结果。在整个试验过程中，患者完成一份每日日记，其中包括BPI简表中的问题，以及关于其他镇痛药使用情况、健康变化和不良事件发生情况的问题。在与研究协调员的电话通话中，每周完成BPI和NPS，在门诊就诊时（即筛查、基线、第1阶段结束和终止时的就诊）进行MSQOL-54评估。主要结局指标是两个研究阶段各自最后维持周期间的平均疼痛强度评分。
共有12名患者入组并至少完成了研究的第一阶段。10名患者为女性。平均（标准差）年龄为49.3（11.7）岁，平均（标准差）体重为76.5（19.9）kg。分析显示，在任何与疼痛或生活质量相关的研究结局方面，拉莫三嗪期和安慰剂期之间均无显著差异。关于不良事件，1名患者在研究期间出现中度皮疹，但医生将此病变归因于带状疱疹；该患者完成了研究。虽然其他不良事件为轻度，但2名患者在第一个研究阶段出现不良事件后退出研究；1名接受拉莫三嗪治疗，另1名接受安慰剂治疗。
该试点试验的结果不支持在MS相关性CP患者中使用拉莫三嗪，也不支持进行更大规模试验的必要性。
