急性发作的处理
The self-administration of simple analgesics, such as paracetamol and ibuprofen [
]How do ibuprofen, triptans and paracetamol affect outcomes in children with migraine?http://cochraneclinicalanswers.com/doi/10.1002/cca.1335/full显示答案
是处理急性发作的合理首选方法。[26]Silver S, Gano D, Gerretsen P. Acute treatment of paediatric migraine: a meta-analysis of efficacy. J Paediatr Child Health. 2008 Jan;44(1-2):3-9.http://www.ncbi.nlm.nih.gov/pubmed/17854415?tool=bestpractice.com[27]Richer L, Billinghurst L, Linsdell MA, et al. Drugs for the acute treatment of migraine in children and adolescents. Cochrane Database Syst Rev. 2016;(4):CD005220.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005220.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27091010?tool=bestpractice.com 由于高退出率 (17%) 和至今未能在交叉试验结果发布前报告结果,导致与来自良好设计研究的获益的证据不足。交叉后继续治疗的作用和组间不平等的退出,可能会导致结果偏倚。几乎没有证据表明对乙酰氨基酚比布洛芬更有效,并且频繁应用两种药物都会引起镇痛药相关的头痛。对乙酰氨基酚的不良反应罕见,但是过量应用可能导致肝损伤;布洛芬偶尔可能导致少数人发生胃肠道不适和超敏反应。
如果简单的镇痛药被证实无效,则可待因可能是某些执业医师的下一步选择(和最终选择),但是 12 岁以下儿童忌用可待因,也不建议在肥胖或患有诸如阻塞性睡眠呼吸暂停或严重肺病等疾病的 12-18 岁青少年中使用可待因,因为这可能会增加出现呼吸问题的风险。[28]US Food and Drug Administration. FDA drug safety communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. April 2017 [internet publication].https://www.fda.gov/Drugs/DrugSafety/ucm549679.htm 通常建议仅用于治疗≥12 岁儿童的其他镇痛药治疗不成功的急性中度疼痛。[29]Medicines and Healthcare Products Regulatory Agency. Codeine: restricted use as analgesic in children and adolescents after European safety review. Drug Safety Update. 2013 June;6(11):S1.http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON287006[30]European Medicines Agency. Restrictions on use of codeine for pain relief in children - CMDh endorses PRAC recommendation. June 2013 [internet publication].http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_001829.jsp&mid=WC0b01ac058004d5c1 目前缺乏有力的获益证据,并且发生不良反应的风险高。镇静和便秘是相对常见的不良反应,且过量应用时会出现呼吸抑制。可待因治疗应在最短时间使用最小有效剂量,且治疗不超过 3 天。[29]Medicines and Healthcare Products Regulatory Agency. Codeine: restricted use as analgesic in children and adolescents after European safety review. Drug Safety Update. 2013 June;6(11):S1.http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON287006[30]European Medicines Agency. Restrictions on use of codeine for pain relief in children - CMDh endorses PRAC recommendation. June 2013 [internet publication].http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_001829.jsp&mid=WC0b01ac058004d5c1
对于出现突然发作(包括呕吐)的患儿,止吐剂(例如苯甲嗪)可能有助于缓解这些症状,并增强其他口服治疗的效果。建议发作时尽早应用这些药物。
For children with refractory symptoms, a 5-HT1 agonist such as intranasal sumatriptan may be considered. [
]How do ibuprofen, triptans and paracetamol affect outcomes in children with migraine?http://cochraneclinicalanswers.com/doi/10.1002/cca.1335/full显示答案
目前的已发表试验(但是纳入的患者群较小)似乎支持使用鼻用舒马普坦,并且在英国已批准 12 岁及以上儿童使用。[27]Richer L, Billinghurst L, Linsdell MA, et al. Drugs for the acute treatment of migraine in children and adolescents. Cochrane Database Syst Rev. 2016;(4):CD005220.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005220.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27091010?tool=bestpractice.com症状缓解:有高质量的证据表明,与安慰剂相比,鼻用舒马普坦在减轻 17 岁以下儿童偏头痛症状方面更有效。系统评价或者受试者>200名的随机对照临床试验(RCT)。 在发作时应尽快使用。据报道,不良反应(嗅觉和味觉障碍)见于大约 20% 的使用者。支持应用口服舒马普坦的资料很少,但其在英国获准用于 6 岁及以上儿童,且在其他领域可超适应证使用。[13]Barnes N, Millman G, James E. Migraine headache in children. Clin Evid. 2006;15:469-475.http://www.ncbi.nlm.nih.gov/pubmed/16973019?tool=bestpractice.com[31]Brenner M, Lewis D. The treatment of migraine headaches in children and adolescents. J Pediatr Pharmacol Ther. 2008 Jan;13(1):17-24.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462052/http://www.ncbi.nlm.nih.gov/pubmed/23055860?tool=bestpractice.com[32]Damen L, Bruijn JK, Verhagen AP, et al. Symptomatic treatment of migraine in children: a systematic review of medication trials. Pediatrics. 2005 Aug;116(2):e295-302.http://pediatrics.aappublications.org/content/116/2/e295.longhttp://www.ncbi.nlm.nih.gov/pubmed/16061583?tool=bestpractice.com[33]Eiland LS, Hunt MO. The use of triptans for pediatric migraines. Paediatr Drugs. 2010 Dec 1;12(6):379-89.http://www.ncbi.nlm.nih.gov/pubmed/21028917?tool=bestpractice.com
除了舒马普坦,支持使用其他同类药物的证据缓慢增多。目前没有足够的数据,无法推荐使用口服佐米曲普坦。[26]Silver S, Gano D, Gerretsen P. Acute treatment of paediatric migraine: a meta-analysis of efficacy. J Paediatr Child Health. 2008 Jan;44(1-2):3-9.http://www.ncbi.nlm.nih.gov/pubmed/17854415?tool=bestpractice.com 然而一项研究发现,在减轻青少年偏头痛症状方面,鼻用佐米曲普坦优于安慰剂,且耐受性良好。最常被报道的副作用是味觉障碍、鼻腔不适和鼻充血,累及大约 20% 的患者。[34]Lewis DW, Winner P, Hershey AD, et al; Adolescent Migraine Steering Committee. Efficacy of zolmitriptan nasal spray in adolescent migraine. Pediatrics. 2007 Aug;120(2):390-6.http://www.ncbi.nlm.nih.gov/pubmed/17671066?tool=bestpractice.com 尽管还没有证据明确支持将口服利扎曲普坦应用于儿童,但口服利扎曲坦已获准在美国使用(用于 6 岁及以上儿童),而在英国仍未获批准使用。[35]Winner P, Lewis D, Visser WH, et al; Rizatriptan Adolescent Study Group. Rizatriptan 5 mg for the acute treatment of migraine in adolescents: a randomized, double-blind, placebo-controlled study. Headache. 2002 Jan;42(1):49-55.http://www.ncbi.nlm.nih.gov/pubmed/12005275?tool=bestpractice.com[36]Bailey B, McManus BC. Treatment of children with migraine in the emergency department: a qualitative systematic review. Pediatr Emerg Care. 2008 May;24(5):321-30.http://www.ncbi.nlm.nih.gov/pubmed/18496120?tool=bestpractice.com[37]Ho TW, Pearlman E, Lewis D, et al. Efficacy and tolerability of rizatriptan in pediatric migraineurs: results from a randomized, double-blind, placebo-controlled trial using a novel adaptive enrichment design. Cephalalgia. 2012 Jul;32(10):750-65.http://www.ncbi.nlm.nih.gov/pubmed/22711898?tool=bestpractice.com 口服阿莫曲普坦在美国获准用于青少年(12 岁及以上),但在其他一些国家未获得许可。关于临床获益的证据来自一项双盲、安慰剂对照、平行组试验,患者年龄为 12-17 岁。[38]Linder SL, Mathew NT, Cady RK, et al. Efficacy and tolerability of almotriptan in adolescents: a randomized, double-blind, placebo-controlled trial. Headache. 2008 Oct;48(9):1326-36.http://www.ncbi.nlm.nih.gov/pubmed/18484981?tool=bestpractice.com 发布的其他儿科数据仅限于两项小型开放性研究。[39]Charles JA. Almotriptan in the acute treatment of migraine in patients 11-17 years old: an open-label pilot study of efficacy and safety. J Headache Pain. 2006 Apr;7(2):95-7.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3451700/pdf/10194_2006_Article_288.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/16688412?tool=bestpractice.com[40]Berenson F, Vasconcellos E, Pakalnis A, et al. Long-term, open-label safety study of oral almotriptan 12.5 mg for the acute treatment of migraine in adolescents. Headache. 2010 May;50(5):795-807.http://www.ncbi.nlm.nih.gov/pubmed/20546320?tool=bestpractice.com [
]How do triptans compare with placebo in adolescents with migraine?http://cochraneclinicalanswers.com/doi/10.1002/cca.1334/full显示答案
针对急性发作,一些临床试验证据支持使用包括曲普坦类药物和非甾体抗炎药 (NSAID) 的联合治疗。[41]Derosier FJ, Lewis D, Hershey AD, et al. Randomized trial of sumatriptan and naproxen sodium combination in adolescent migraine. Pediatrics. 2012 Jun;129(6):e1411-20.http://www.ncbi.nlm.nih.gov/pubmed/22585767?tool=bestpractice.com
反复发作的治疗
当偏头痛的发作频率和严重程度影响到学校和社会生活时,预防性药物治疗可能适用,尤其是简单的非处方镇痛药对终止发作无效的情况下。[42]Eiland LS, Jenkins LS, Durham SH. Pediatric migraine: pharmacologic agents for prophylaxis. Ann Pharmacother. 2007 Jul;41(7):1181-90.http://www.ncbi.nlm.nih.gov/pubmed/17550953?tool=bestpractice.com
如果需要预防性药物治疗,建议避免多药联合治疗。对于每种预防性药物,均应在初始预防性应用后大约 3 个月时进行评估。若症状无改善,应停用并代之另一种药物。如果实际可行,最好避免在儿童中长期预防性用药。应定期停用对个体儿童明显有益的药物(至少每年一次),并回顾症状以评估预防性用药是否仍有必要。
支持预防性用药的证据在缓慢增多,但仍不清楚哪种药物有最好的治疗反应。可考虑的预防性药物包括普萘洛尔、苯噻啶和托吡酯。已发表的研究中关于普萘洛尔有益的证据是矛盾的,它不应该用于哮喘儿童。运动员(需要使用肾上腺素来帮助他们提高成绩)可能不愿使用该有。目前无明确证据支持苯噻啶的常规使用,但在有这种药物的国家仍被广泛处方应用。症状缓解:尽管被广泛用于该适应证,但尚无来自良好设计试验的证据表明苯噻啶对治疗儿童偏头痛有益。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。 大量研究已对托吡酯进行了评估,部分研究通过一些终点发现它是有益的。然而,随机对照试验的结果与依据结局指标分析的结果存在差异,因此不能给出支持其使用的可靠推荐。[43]El-Chammas K, Keyes J, Thompson N, et al. Pharmacologic treatment of pediatric headaches: a meta-analysis. JAMA Pediatr. 2013 Mar 1;167(3):250-8.http://archpedi.jamanetwork.com/article.aspx?articleid=1558560http://www.ncbi.nlm.nih.gov/pubmed/23358935?tool=bestpractice.com症状缓解:有低质量的证据表明,与安慰剂相比,托吡酯在减少 3-5 个月期间的头痛发作频率方面更有效。然而,随机对照试验的结果与依据结局指标分析的结果存在差异。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。 在美国,已批准托吡酯用于预防 12-17 岁青少年偏头痛。
持续出现导致失能的发作可能表明需使用其他药物:阿米替林、丙戊酸、卡马西平和加巴喷丁,但每种药物开始使用都需要由主任医生批准,并且要严密监测不良反应。阿米替林优于抗惊厥药物治疗,对于高度耐药的病例,维拉帕米和吲哚美辛也值得考虑。[2]Ryan S. Medicines for migraine. Arch Dis Child Educ Pract Ed. 2007;92:ep50-ep55.http://www.ncbi.nlm.nih.gov/pubmed/17430855?tool=bestpractice.com2018 年,欧洲药品管理局 (EMA) 最终完成了对丙戊酸及其类似物的审查,并建议在妊娠期禁止将这些药物用于偏头痛预防治疗,因为胎儿/儿童存在先天畸形和出现发育问题的风险。[44]European Medicines Agency. New measures to avoid valproate exposure in pregnancy endorsed. EMA/145600/2018. March 2018 [internet publication].http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2018/03/WC500246391.pdf 在美国,禁止对妊娠女性使用丙戊酸及其类似物预防偏头痛。在欧洲和美国,除非已实施妊娠预防计划并且符合特定的条件,否则丙戊酸及其类似药物不得用于育龄期女性患者。[44]European Medicines Agency. New measures to avoid valproate exposure in pregnancy endorsed. EMA/145600/2018. March 2018 [internet publication].http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2018/03/WC500246391.pdf