Linde Mattias, Mulleners Wim M, Chronicle Edward P, McCrory Douglas C
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
Cochrane Database Syst Rev. 2013 Jun 24;2013(6):CD010609. doi: 10.1002/14651858.CD010609.
Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs in the central nervous system. The present review is part of an update of a Cochrane review first published in 2004, and previously updated (conclusions not changed) in 2007.
To describe and assess the evidence from controlled trials on the efficacy and tolerability of gabapentin/gabapentin enacarbil or pregabalin for preventing migraine attacks in adult patients with episodic migraine.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2012, Issue 12), PubMed/MEDLINE (1966 to 15 January 2013), MEDLINE In-Process (current week, 15 January 2013), and EMBASE (1974 to 15 January 2013) and handsearched Headache and Cephalalgia through January 2013.
Studies were required to be prospective, controlled trials of gabapentin/gabapentin enacarbil or pregabalin taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both.
Two review authors independently selected studies and extracted data. For headache frequency data, we calculated mean differences (MDs) between gabapentin and comparator (placebo, active control, or gabapentin in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with ≥ 50% reduction in headache frequency), we calculated odds ratios (ORs) and numbers needed to treat (NNTs). We also summarised data on adverse events from all single dosage studies and calculated risk differences (RDs) and numbers needed to harm (NNHs).
Five trials on gabapentin and one trial on its prodrug gabapentin enacarbil met the inclusion criteria; no reports on pregabalin were identified. In total, data from 1009 patients were considered. One trial each of gabapentin 900 mg (53 patients), and gabapentin titrated to 1200 mg (63 patients) and 1800 mg (122 patients) failed to show a statistically significant reduction in headache frequency in the active treatment group as compared to the placebo group, whereas one trial of gabapentin titrated to 1800 to 2400 mg (113 patients) demonstrated a small but statistically significant superiority of active treatment for this outcome (MD -0.80; 95% confidence interval (CI) -1.55 to -0.05). The pooled results of these four studies (MD -0.44; 95% CI -1.43 to 0.56; 351 patients) do not demonstrate a significant difference between gabapentin and placebo. One trial of gabapentin titrated to 1800 mg (122 patients) failed to demonstrate a significant difference between active treatment and placebo in the proportion of responders (OR 0.97; 95% CI 0.45 to 2.11), whereas one trial of gabapentin titrated to 1800 to 2400 mg (113 patients) demonstrated a small but statistically significant superiority of active treatment for this outcome (OR 2.79; 95% CI 1.09 to 7.17). The pooled results of these two studies (OR 1.59; 95% CI 0.57 to 4.46; 235 patients) do not demonstrate a significant difference between gabapentin and placebo. Comparisons from one study (135 patients) suggest that gabapentin 2000 mg is no more effective than gabapentin 1200 mg. One trial of gabapentin enacarbil (523 participants) failed to demonstrate a significant difference versus placebo or between doses for gabapentin enacarbil titrated to between 1200 mg and 3000 mg with regard to proportion of responders; there was also no evidence of a dose-response trend. Adverse events, most notably dizziness and somnolence, were common with gabapentin.
AUTHORS' CONCLUSIONS: The pooled evidence derived from trials of gabapentin suggests that it is not efficacious for the prophylaxis of episodic migraine in adults. Since adverse events were common among the gabapentin-treated patients, it is advocated that gabapentin should not be used in routine clinical practice. Gabapentin enacarbil is not efficacious for the prophylaxis of episodic migraine in adults. There is no published evidence from controlled trials of pregabalin for the prophylaxis of episodic migraine in adults.
在临床实践中，某些抗癫痫药物对偏头痛的预防有效，而其他药物则不然。这可能是由于这些药物在中枢神经系统中的多种作用所致。本综述是Cochrane综述更新的一部分，该综述首次发表于2004年，此前于2007年进行过更新（结论未变）。
描述和评估来自对照试验的证据，以证明加巴喷丁/加巴喷丁依那卡比或普瑞巴林预防发作性偏头痛成年患者偏头痛发作的疗效和耐受性。
我们检索了Cochrane对照试验中心注册库（CENTRAL；《Cochrane图书馆》2012年第12期）、PubMed/MEDLINE（1966年至2013年1月15日）、MEDLINE在研数据库（当前周，2013年1月15日）和EMBASE（1974年至2013年1月15日），并手工检索了截至2013年1月的《头痛与头面痛杂志》。
研究需为前瞻性对照试验，定期服用加巴喷丁/加巴喷丁依那卡比或普瑞巴林以预防偏头痛发作，改善偏头痛相关生活质量，或两者兼具。
两位综述作者独立选择研究并提取数据。对于头痛频率数据，我们计算了各研究中加巴喷丁与对照（安慰剂、活性对照或不同剂量加巴喷丁）之间的平均差值（MDs），并对各研究结果进行汇总。对于反应者的二分数据（头痛频率降低≥50%的患者），我们计算了比值比（ORs）和治疗所需人数（NNTs）。我们还总结了所有单剂量研究中的不良事件数据，并计算了风险差值（RDs）和伤害所需人数（NNHs）。
五项关于加巴喷丁的试验和一项关于其前体药物加巴喷丁依那卡比的试验符合纳入标准；未检索到关于普瑞巴林的报告。总共纳入了1009例患者的数据。加巴喷丁900mg的一项试验（53例患者）、加巴喷丁滴定至1200mg的一项试验（63例患者）和加巴喷丁滴定至1800mg的一项试验（122例患者）均未显示活性治疗组与安慰剂组相比头痛频率有统计学显著降低，而加巴喷丁滴定至1800至2400mg的一项试验（113例患者）显示活性治疗在该结果上有小但统计学显著的优势（MD -0.80；95%置信区间（CI）-1.55至-0.05）。这四项研究的汇总结果（MD -0.44；95%CI -1.43至0.56；351例患者）未显示加巴喷丁与安慰剂之间有显著差异。加巴喷丁滴定至1800mg的一项试验（122例患者）未显示活性治疗与安慰剂在反应者比例上有显著差异（OR 0.97；95%CI 0.45至2.11），而加巴喷丁滴定至1800至2400mg的一项试验（113例患者）显示活性治疗在该结果上有小但统计学显著的优势（OR 2.79；95%CI 1.09至7.17）。这两项研究的汇总结果（OR 1.59；95%CI 0.57至4.46；235例患者）未显示加巴喷丁与安慰剂之间有显著差异。一项研究（135例患者）的比较表明，加巴喷丁2000mg并不比加巴喷丁1200mg更有效。一项加巴喷丁依那卡比试验（523名参与者）未显示与安慰剂相比或加巴喷丁依那卡比滴定至1200mg至3000mg之间各剂量在反应者比例上有显著差异；也没有剂量反应趋势的证据。不良事件，最常见的是头晕和嗜睡，在加巴喷丁治疗的患者中很常见。
来自加巴喷丁试验的汇总证据表明，它对成人发作性偏头痛的预防无效。由于加巴喷丁治疗的患者中不良事件很常见，因此主张在常规临床实践中不应使用加巴喷丁。加巴喷丁依那卡比对成人发作性偏头痛的预防无效。没有关于普瑞巴林预防成人发作性偏头痛的对照试验的已发表证据。
