Richer Lawrence, Billinghurst Lori, Linsdell Meghan A, Russell Kelly, Vandermeer Ben, Crumley Ellen T, Durec Tamara, Klassen Terry P, Hartling Lisa
Department of Pediatrics, Division of Neurology, University of Alberta, 4-478 Edmonton Clinic Health Academy, 11405 - 87 Avenue, Edmonton, AB, Canada, T6G 1C9.
Cochrane Database Syst Rev. 2016 Apr 19;4(4):CD005220. doi: 10.1002/14651858.CD005220.pub2.
Numerous medications are available for the acute treatment of migraine in adults, and some have now been approved for use in children and adolescents in the ambulatory setting. A systematic review of acute treatment of migraine medication trials in children and adolescents will help clinicians make evidence-informed management choices.
To assess the effects of pharmacological interventions by any route of administration versus placebo for migraine in children and adolescents 17 years of age or less. For the purposes of this review, children were defined as under 12 years of age and adolescents 12 to 17 years of age.
We searched seven bibliographic databases and four clinical trial registers as well as gray literature for studies through February 2016.
We included prospective randomized controlled clinical trials of children and adolescents with migraine, comparing acute symptom relieving migraine medications with placebo in the ambulatory setting.
Two reviewers screened titles and abstracts and reviewed the full text of potentially eligible studies. Two independent reviewers extracted data for studies meeting inclusion criteria. We calculated the risk ratios (RRs) and number needed to treat for an additional beneficial outcome (NNTB) for dichotomous data. We calculated the risk difference (RD) and number needed to treat for an additional harmful outcome (NNTH) for proportions of adverse events. The percentage of pain-free patients at two hours was the primary efficacy outcome measure. We used adverse events to evaluate safety and tolerability. Secondary outcome measures included headache relief, use of rescue medication, headache recurrence, presence of nausea, and presence of vomiting. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables.
We identified a total of 27 randomized controlled trials (RCTs) of migraine symptom-relieving medications, in which 9158 children and adolescents were enrolled and 7630 (range of mean age between 8.2 and 14.7 years) received medication. Twenty-four studies focused on drugs in the triptan class, including almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, sumatriptan + naproxen sodium, and zolmitriptan. Other medications studied included paracetamol (acetaminophen), ibuprofen, and dihydroergotamine (DHE). More than half of the studies evaluated sumatriptan. All but one study reported adverse event data. Most studies presented a low or unclear risk of bias, and the overall quality of evidence, according to GRADE criteria, was low to moderate, downgraded mostly due to imprecision and inconsistency. Ibuprofen was more effective than placebo for producing pain freedom at two hours in two small studies that included 162 children (RR 1.87, 95% confidence interval (CI) 1.15 to 3.04) with low quality evidence (due to imprecision). Paracetamol was not superior to placebo in one small study of 80 children. Triptans as a class of medication were superior to placebo in producing pain freedom in 3 studies involving 273 children (RR 1.67, 95% CI 1.06 to 2.62, NNTB 13) (moderate quality evidence) and 21 studies involving 7026 adolescents (RR 1.32, 95% CI 1.19 to 1.47, NNTB 6) (moderate quality evidence). There was no significant difference in the effect sizes between studies involving children versus adolescents. Triptans were associated with an increased risk of minor (non-serious) adverse events in adolescents (RD 0.13, 95% CI 0.08 to 0.18, NNTH 8), but studies did not report any serious adverse events. The risk of minor adverse events was not significant in children (RD 0.06, 95% CI - 0.04 to 0.17, NNTH 17). Sumatriptan plus naproxen sodium was superior to placebo in one study involving 490 adolescents (RR 3.25, 95% CI 1.78 to 5.94, NNTB 6) (moderate quality evidence). Oral dihydroergotamine was not superior to placebo in one small study involving 13 children.
AUTHORS' CONCLUSIONS: Low quality evidence from two small trials shows that ibuprofen appears to improve pain freedom for the acute treatment of children with migraine. We have only limited information on adverse events associated with ibuprofen in the trials included in this review. Triptans as a class are also effective at providing pain freedom in children and adolescents but are associated with higher rates of minor adverse events. Sumatriptan plus naproxen sodium is also effective in treating adolescents with migraine.
有多种药物可用于成人偏头痛的急性治疗，目前一些药物已获批用于儿童和青少年的门诊治疗。对儿童和青少年偏头痛药物急性治疗试验进行系统评价，将有助于临床医生做出基于证据的管理选择。
评估17岁及以下儿童和青少年偏头痛采用任何给药途径的药物干预与安慰剂相比的效果。在本评价中，儿童定义为12岁以下，青少年定义为12至17岁。
我们检索了7个书目数据库、4个临床试验注册库以及灰色文献，以查找截至2016年2月的研究。
我们纳入了偏头痛儿童和青少年的前瞻性随机对照临床试验，比较门诊环境中急性缓解症状的偏头痛药物与安慰剂。
两名评价员筛选标题和摘要，并对可能符合条件的研究全文进行审查。两名独立评价员提取符合纳入标准的研究数据。我们计算了二分数据的风险比（RRs）和获得额外有益结果所需的治疗人数（NNTB）。我们计算了不良事件比例的风险差（RD）和获得额外有害结果所需的治疗人数（NNTH）。两小时无痛患者的百分比是主要疗效指标。我们使用不良事件来评估安全性和耐受性。次要疗效指标包括头痛缓解、急救药物使用、头痛复发、恶心的存在和呕吐的存在。我们使用GRADE（推荐分级评估、制定和评价）评估证据，并创建“结果总结”表。
我们共识别出27项偏头痛症状缓解药物的随机对照试验（RCT），其中9158名儿童和青少年入组，7630名（平均年龄范围为8.2至14.7岁）接受了药物治疗。24项研究聚焦于曲坦类药物，包括阿莫曲坦、依立曲坦、那拉曲坦、利扎曲坦、舒马曲坦、舒马曲坦+萘普生钠和佐米曲坦。其他研究的药物包括对乙酰氨基酚、布洛芬和双氢麦角胺（DHE）。超过一半的研究评估了舒马曲坦。除一项研究外，所有研究均报告了不良事件数据。大多数研究呈现出低或不明确的偏倚风险，根据GRADE标准，总体证据质量为低到中等，主要因不精确和不一致而降级。在两项纳入162名儿童的小型研究中，布洛芬在两小时产生无痛方面比安慰剂更有效（RR 1.87，95%置信区间（CI）1.15至3.04），证据质量低（因不精确）。在一项纳入80名儿童的小型研究中，对乙酰氨基酚并不优于安慰剂。在3项纳入273名儿童的研究中（RR 1.67，95% CI 1.06至2.62，NNTB 13）（中等质量证据）以及21项纳入7026名青少年的研究中（RR 1.32，95% CI 1.19至1.47，NNTB 6）（中等质量证据）。涉及儿童与青少年的研究之间效应大小无显著差异。曲坦类药物与青少年轻微（非严重）不良事件风险增加相关（RD 0.13，95% CI 0.08至0.18，NNTH 8），但研究未报告任何严重不良事件。儿童轻微不良事件风险不显著（RD 0.06，95% CI -0.04至0.17，NNTH 17）。在一项纳入490名青少年的研究中，舒马曲坦加萘普生钠优于安慰剂（RR 3.25，95% CI 1.78至5.94，NNTB 6）（中等质量证据）。在一项纳入13名儿童的小型研究中，口服双氢麦角胺并不优于安慰剂。
两项小型试验的低质量证据表明，布洛芬似乎能改善偏头痛儿童急性治疗时的无痛状态。在本评价纳入的试验中，我们关于布洛芬相关不良事件的信息有限。曲坦类药物总体上在儿童和青少年中也能有效实现无痛，但与较高的轻微不良事件发生率相关。舒马曲坦加萘普生钠在治疗青少年偏头痛方面也有效。
