Beard S, Hunn A, Wight J
School of Health and Related Research (ScHARR), University of Sheffield, UK.
Health Technol Assess. 2003;7(40):iii, ix-x, 1-111. doi: 10.3310/hta7400.
To identify the drug treatments currently available for the management of spasticity and pain in multiple sclerosis (MS), and to evaluate their clinical and cost-effectiveness.
Electronic bibliographic databases, National Research Register, MRC Clinical Trials Register and the US National Institutes of Health Clinical Trials Register.
Systematic searches identified 15 interventions for the treatment of spasticity and 15 interventions for treatment of pain. The quality and outcomes of the studies were evaluated. Reviews of the treatment of spasticity and pain when due to other aetiologies were also sought.
There is limited evidence of the effectiveness of four oral drugs for spasticity: baclofen, dantrolene, diazepam and tizanidine. Tizanidine appears to be no more effective than comparator drugs such as baclofen and has a slightly different side-effects profile. Despite claims that it causes less muscle weakness, there was very little evidence that tizanidine performed any better in this respect than other drugs, although it is more expensive. The findings of this review are consistent with reviews of the same treatments for spasticity derived from other aetiologies. There is good evidence that both botulinum toxin (BT) and intrathecal baclofen are effective in reducing spasticity, and both are associated with functional benefit. However, they are invasive, and substantially more expensive. None of the studies included in the review of pain were designed specifically to evaluate the alleviation of pain in patients with MS and there was no consistency regarding the use of validated outcome measures. It was suggested that, although expensive, the use of intrathecal baclofen may be associated with significant savings in hospitalisation costs in relation to bed-bound patients who are at risk of developing pressure sores, thus enhancing its cost-effectiveness. No studies of cost-effectiveness were identified in the review of pain. There is evidence, albeit limited, of the clinical effectiveness of baclofen, dantrolene, diazepam, tizanidine, intrathecal baclofen and BT and of the potential cost-effectiveness of intrathecal baclofen in the treatment of spasticity in MS.
Many of the interventions identified are not licensed for the alleviation of pain or spasticity in MS and the lack of evidence relating to their effectiveness may also limit their widespread use. Indeed, forthcoming information relating to the use of cannabinoids in MS may result in there being better evidence of the effectiveness of new treatments than of any of the currently used drugs. It may therefore be of value to carry out double-blind randomised controlled trials of interventions used in current practice, where outcomes could include functional benefit and impact on quality of life. Further research into the development and validation of outcomes measures for pain and spasticity may also be useful, as perhaps would cost-utility studies.
确定目前可用于治疗多发性硬化症（MS）痉挛和疼痛的药物治疗方法，并评估其临床效果和成本效益。
电子文献数据库、国家研究注册库、医学研究委员会临床试验注册库和美国国立卫生研究院临床试验注册库。
系统检索确定了15种治疗痉挛的干预措施和15种治疗疼痛的干预措施。对研究的质量和结果进行了评估。还检索了其他病因引起的痉挛和疼痛治疗的综述。
有有限证据表明四种口服药物对痉挛有效：巴氯芬、丹曲林、地西泮和替扎尼定。替扎尼定似乎并不比巴氯芬等对照药物更有效，且副作用略有不同。尽管有人声称它引起的肌肉无力较少，但几乎没有证据表明替扎尼定在这方面比其他药物表现更好，尽管它更昂贵。本综述的结果与其他病因引起的痉挛相同治疗方法的综述一致。有充分证据表明肉毒杆菌毒素（BT）和鞘内注射巴氯芬在减轻痉挛方面有效，且两者都与功能改善相关。然而，它们具有侵入性，且成本高得多。疼痛综述中纳入的研究均未专门设计用于评估MS患者疼痛的缓解情况，且在使用经过验证的结局指标方面也不一致。有人认为，尽管鞘内注射巴氯芬价格昂贵，但对于有发生压疮风险的卧床患者，使用它可能会显著节省住院费用，从而提高其成本效益。疼痛综述中未发现成本效益研究。有证据表明，尽管有限，但巴氯芬、丹曲林、地西泮、替扎尼定、鞘内注射巴氯芬和BT在治疗MS痉挛方面具有临床有效性，且鞘内注射巴氯芬具有潜在的成本效益。
所确定的许多干预措施未获许可用于缓解MS的疼痛或痉挛，且缺乏其有效性的证据也可能限制其广泛使用。事实上，即将出台的有关MS中使用大麻素的信息可能会使新治疗方法有效性的证据比任何目前使用的药物都更好。因此，对当前实践中使用的干预措施进行双盲随机对照试验可能具有价值，试验结果可包括功能改善和对生活质量的影响。对疼痛和痉挛结局指标的开发和验证进行进一步研究可能也有用，成本效用研究可能也是如此。
