Wiffen Philip J, Collins Sally, McQuay Henry J, Carroll Dawn, Jadad Alejandro, Moore R Andrew
UK Cochrane Centre, National Institute for Health Research, Summertown Pavilion, Middle Way, Oxford, UK, OX2 7LG.
Cochrane Database Syst Rev. 2010 Jan 20;2010(1):CD001133. doi: 10.1002/14651858.CD001133.pub3.
Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. Readers are referred to reviews of carbamazepine and gabapentin in T he Cochrane Library which replace the information on those drugs in this review. Other drugs remain unchanged at present in this review
To evaluate the analgesic effectiveness and adverse effects of anticonvulsant drugs for pain management in clinical practice . Migraine and headache studies are excluded in this revision.
Randomised trials of anticonvulsants in acute, chronic or cancer pain were identified by MEDLINE (1966-1999), EMBASE (1994-1999), SIGLE (1980 to 1999) and the Cochrane Controlled Trials Register (CENTRAL/CCTR) (The Cochrane Library Issue 3, 1999). In addition, 41 medical journals were hand searched. Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: September 1999.
Randomised trials reporting the analgesic effects of anticonvulsant drugs in patients, with subjective pain assessment as either the primary or a secondary outcome.
Data were extracted by two independent review authors, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal, for individual studies and for pooled data.
Twenty-three trials of six anticonvulsants were considered eligible (1074 patients).The only placebo-controlled study in acute pain found no analgesic effect of sodium valproate.Three placebo-controlled studies of carbamazepine in trigeminal neuralgia had a combined NNT (95% confidence interval (CI)) for effectiveness of 2.5 (CI 2.0 to 3.4). A single placebo-controlled trial of gabapentin in post-herpetic neuralgia had an NNT of 3.2 (CI 2.4 to 5.0). For diabetic neuropathy NNTs for effectiveness were as follows: (one RCT for each drug) carbamazepine 2.3 (CI 1.6 to 3.8), gabapentin 3.8 (CI 2.4 to 8.7) and phenytoin 2.1 (CI 1.5 to 3.6).Numbers-needed-to-harm (NNHs) were calculated where possible by combining studies for each drug entity irrespective of the condition treated. The results were, for minor harm, carbamazepine 3.7 (CI 2.4 to 7.8), gabapentin 2.5 (CI 2.0 to 3.2), phenytoin 3.2 (CI 2.1 to 6.3). NNHs for major harm were not statistically significant for any drug compared with placebo.Phenytoin had no effect in irritable bowel syndrome, and carbamazepine little effect in post-stroke pain. Clonazepam was effective in one study of temporomandibular joint dysfunction.
AUTHORS' CONCLUSIONS: Although anticonvulsants are used widely in chronic pain surprisingly few trials show analgesic effectiveness. Only one study identified considered cancer pain. There is no evidence that anticonvulsants are effective for acute pain. In chronic pain syndromes other than trigeminal neuralgia, anticonvulsants should be withheld until other interventions have been tried. While gabapentin is increasingly being used for neuropathic pain the evidence would suggest that it is not superior to carbamazepine.
自20世纪60年代以来,抗惊厥药物就被用于疼痛管理。临床印象是它们对慢性神经性疼痛有用,尤其是当疼痛呈刺痛或灼痛时。读者可参考《考科蓝图书馆》中关于卡马西平和加巴喷丁的综述,该综述取代了本综述中关于这些药物的信息。目前本综述中其他药物保持不变。
评估抗惊厥药物在临床实践中用于疼痛管理的镇痛效果和不良反应。本次修订排除偏头痛和头痛研究。
通过MEDLINE(1966 - 1999年)、EMBASE(1994 - 1999年)、SIGLE(1980至1999年)和考科蓝对照试验注册库(CENTRAL/CCTR)(《考科蓝图书馆》1999年第3期)确定抗惊厥药物在急性、慢性或癌痛中的随机试验。此外,还手工检索了41种医学期刊。从检索到的论文参考文献列表以及通过联系研究者确定了其他报告。最近一次检索日期:1999年9月。
报告抗惊厥药物对患者镇痛效果的随机试验,以主观疼痛评估作为主要或次要结局。
由两名独立的综述作者提取数据,并对试验进行质量评分。根据二分数据计算治疗所需人数(NNT),用于个体研究和汇总数据的有效性、不良反应及与药物相关的研究撤药情况。
六项抗惊厥药物的23项试验被认为符合条件(1074例患者)。急性疼痛中唯一一项安慰剂对照研究发现丙戊酸钠无镇痛效果。三项卡马西平治疗三叉神经痛的安慰剂对照研究合并后有效性的NNT(95%置信区间(CI))为2.5(CI 2.0至3.4)。加巴喷丁治疗带状疱疹后神经痛的一项安慰剂对照试验NNT为3.2(CI 2.4至5.0)。对于糖尿病性神经病变,有效性的NNT如下:(每种药物一项随机对照试验)卡马西平2.3(CI 1.6至3.8),加巴喷丁3.8(CI 2.4至8.7),苯妥英2.1(CI 1.5至3.6)。尽可能通过合并每种药物实体的研究计算伤害所需人数(NNH),无论治疗的疾病如何。结果显示,对于轻微伤害,卡马西平3.7(CI 2.4至7.8),加巴喷丁2.5(CI 2.0至3.2),苯妥英3.2(CI 2.1至6.3)。与安慰剂相比,任何药物严重伤害的NNH均无统计学意义。苯妥英对肠易激综合征无效,卡马西平对中风后疼痛效果甚微。氯硝西泮在一项颞下颌关节功能障碍研究中有效。
尽管抗惊厥药物在慢性疼痛中广泛使用,但令人惊讶的是很少有试验显示出镇痛效果。仅确定一项研究考虑了癌痛。没有证据表明抗惊厥药物对急性疼痛有效。在三叉神经痛以外的慢性疼痛综合征中,在尝试其他干预措施之前应停用抗惊厥药物。虽然加巴喷丁越来越多地用于神经性疼痛,但证据表明它并不优于卡马西平。