Moore R Andrew, Wiffen Philip J, Derry Sheena, Lunn Michael P T
Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), University of Oxford, Oxford, UK.
Cochrane Database Syst Rev. 2015 Jan 22;1(1):CD011241. doi: 10.1002/14651858.CD011241.pub2.
Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. The efficacy of zonisamide for the relief of neuropathic pain has not previously been reviewed.
To assess the analgesic efficacy and associated adverse events of zonisamide for chronic neuropathic pain in adults.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (via CRSO), MEDLINE, EMBASE, and two clinical trials databases (ClinicalTrials.gov. and the World Health Organisation Clinical Trials Registry Platform) to 1 August 2014, together with reference lists of retrieved papers and reviews.
We included randomised, double-blind studies of at least two weeks' duration comparing zonisamide with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 and over. We included only full journal publication articles and clinical trial summaries.
Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We considered the evidence using three tiers. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design); second tier evidence derived from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison; and third tier evidence derived from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.We planned to calculate risk ratio (RR) and numbers needed to treat (NNT) and harm (NNH) for one additional event using standard methods expected by The Cochrane Collaboration.
We included a single study treating 25 participants (13 zonisamide, 12 placebo) with painful diabetic neuropathy over 12 weeks. No first or second tier evidence was available for any outcome. The small size of the study and potential major bias due to a high proportion of early study withdrawals with zonisamide precluded any conclusions being drawn. There were two serious adverse events (one death) in zonisamide-treated participants, which were apparently not related to treatment.
AUTHORS' CONCLUSIONS: The review found a lack of evidence suggesting that zonisamide provides pain relief in any neuropathic pain condition. Effective medicines with much greater supportive evidence are available.
自20世纪60年代以来，抗癫痫药物就被用于疼痛管理；一些药物已显示出对不同神经性疼痛病症的治疗效果。此前尚未对唑尼沙胺缓解神经性疼痛的疗效进行过综述。
评估唑尼沙胺对成人慢性神经性疼痛的镇痛效果及相关不良事件。
我们检索了截至2014年8月1日的Cochrane对照试验中央登记库（CENTRAL）（通过CRSO）、MEDLINE、EMBASE以及两个临床试验数据库（ClinicalTrials.gov和世界卫生组织临床试验注册平台），并查阅了检索到的论文和综述的参考文献列表。
我们纳入了至少为期两周的随机、双盲研究，这些研究比较了唑尼沙胺与安慰剂或其他活性治疗药物在慢性神经性疼痛中的效果。参与者为18岁及以上的成年人。我们仅纳入了完整的期刊发表文章和临床试验总结。
两位综述作者独立提取了疗效和不良事件数据，并检查了研究质量问题。我们使用三个层次来考量证据。第一层次证据来自符合当前最佳标准且偏倚风险最小的数据（结果等同于疼痛强度大幅降低，意向性分析不补全失访数据；比较组中至少有200名参与者，为期8至12周，平行设计）；第二层次证据来自未能满足上述一项或多项标准的数据，这些数据被认为存在一定偏倚风险，但比较组中有足够数量的参与者；第三层次证据来自涉及少量参与者的数据，这些数据被认为极有可能存在偏倚，或使用了临床效用有限的结果，或两者皆有。我们计划使用Cochrane协作网期望的标准方法计算风险比（RR）、需治疗人数（NNT）以及额外发生一例不良事件的伤害人数（NNH）。
我们纳入了一项针对25名患有疼痛性糖尿病神经病变参与者（13名服用唑尼沙胺，12名服用安慰剂）的为期12周的研究。对于任何结果均无第一或第二层次证据。该研究规模较小，且由于服用唑尼沙胺的参与者早期退出比例较高可能存在重大偏倚，因此无法得出任何结论。服用唑尼沙胺的参与者中有两例严重不良事件（一例死亡），显然与治疗无关。
该综述发现，缺乏证据表明唑尼沙胺能缓解任何神经性疼痛病症。有支持证据更多的有效药物可供使用。
