偏头痛是一种慢性病。 治疗的主要目标是找到急性发作的可靠、快速起效并能恢复机能的治疗方法。 治疗应与患者头痛和失能严重程度相匹配。
尚无临床试验可确定一种偏头痛治疗(急性发作期治疗或预防性治疗)优于其他治疗。[109]Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 1: triptans, dihydroergotamine, and magnesium. Headache. 2012 Jan;52(1):114-28.http://www.ncbi.nlm.nih.gov/pubmed/22211870?tool=bestpractice.com[110]Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others. Headache. 2012 Feb;52(2):292-306.http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.2011.02070.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22309235?tool=bestpractice.com[111]Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 3: opioids, NSAIDs, steroids, and post-discharge medications. Headache. 2012 Mar;52(3):467-82.http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.2012.02097.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22404708?tool=bestpractice.com 一般而言,与非特异性治疗相比,优先选择曲普坦类;不过,尚无直接比较曲普坦类的试验。
症状缓解
患者经常在不咨询其医生的情况下自行开始偏头痛和头痛治疗。 偏头痛发作的自我药疗指南建议推荐将包含扑热息痛、阿司匹林和咖啡因的固定剂量复合制剂治疗或者布洛芬、那拉曲坦或扑热息痛单一疗法作为一线疗法。 [112]Haag G, Diener HC, May A, et al. Self-medication of migraine and tension-type headache: summary of the evidence-based recommendations of the Deutsche Migrane und Kopfschmerzgesellschaft (DMKG), the Deutsche Gesellschaft fur Neurologie (DGN), the Osterreichische Kopfschmerzgesellschaft (OKSG) and the Schweizerische Kopfwehgesellschaft (SKG). J Headache Pain. 2011 Apr;12(2):201-17.http://link.springer.com/article/10.1007%2Fs10194-010-0266-4/fulltext.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/21181425?tool=bestpractice.com
在初级保健中,处方剂量强度的非甾体类抗炎药 (NSAID) 可能会是有效的初始治疗方法。[113]Snow V, Weiss K, Wall EM, et al., for the American Academy of Family Physicians, American College of Physicians-American Society of Internal Medicine. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002 Nov 19;137(10):840-9.http://www.annals.org/content/137/10/840.fullhttp://www.ncbi.nlm.nih.gov/pubmed/12435222?tool=bestpractice.com[114]Derry S, Rabbie R, Moore RA. Diclofenac with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;(4):CD008783.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008783.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23633360?tool=bestpractice.com [
]How does diclofenac affect outcomes in adults with acute migraine headaches?https://cochranelibrary.com/cca/doi/10.1002/cca.458/full显示答案
在专科保健或头痛诊所中,治疗通常以 5HT1 受体激动剂(曲普坦)等偏头痛特异性药物开始。[115]Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000 Sep 26;55(6):754-62. Erratum in: Neurology 2000 Jan 9;56(1):142.http://n.neurology.org/content/55/6/754.longhttp://www.ncbi.nlm.nih.gov/pubmed/10993991?tool=bestpractice.com[116]Lipton RB, Stewart WF, Stone AM, et al. Stratified care vs step care strategies for migraine: the Disability in Strategies of Care (DISC) Study: a randomized trial. JAMA. 2000 Nov 22-29;284(20):2599-605.http://jama.ama-assn.org/content/284/20/2599.fullhttp://www.ncbi.nlm.nih.gov/pubmed/11086366?tool=bestpractice.com[117]Lipton RB, Silberstein SD. The role of headache-related disability in migraine management: implications for headache treatment guidelines. Neurology. 2001;56(6 Suppl 1):S35-42.http://www.ncbi.nlm.nih.gov/pubmed/11294958?tool=bestpractice.com[118]Derry CJ, Derry S, Moore RA. Sumatriptan (oral route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev. 2012;(2):CD008615.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008615.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22336849?tool=bestpractice.com 然而,对乙酰氨基酚与止吐剂联用与口服舒马曲坦的疗效相当,并且前者的不良反应较少。[119]Derry S, Moore RA. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;(4):CD008040.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008040.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23633349?tool=bestpractice.com [
]What are the benefits and harms of acetaminophen (paracetamol) with or without an antiemetic in adults with acute migraine headaches?https://cochranelibrary.com/cca/doi/10.1002/cca.216/full显示答案
对于轻度至中度症状,已对适用于偏头痛急性发作期治疗的阿司匹林/扑热息痛/咖啡因复合制剂这一专卖药进行了研究,且该复合制剂专卖药比安慰剂更加有效。[120]Goldstein J, Silberstein SD, Saper JR, et al. Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute migraine: results from a multicenter, double-blind, randomized, parallel-group, single-dose, placebo-controlled study. Headache. 2006 Mar;46(3):444-53.http://www.ncbi.nlm.nih.gov/pubmed/16618262?tool=bestpractice.com[121]Blumenthal HJ, Diamond ML. Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early treatment of migraine: results from the ASSET trial - a comment. Headache. 2006 Feb;46(2):340.http://www.ncbi.nlm.nih.gov/pubmed/16492249?tool=bestpractice.com[122]Diener HC, Pfaffenrath V, Pageler L, et al. The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more effective than single substances and dual combination for the treatment of headache: a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study. Cephalalgia. 2005 Oct;25(10):776-87.http://www.ncbi.nlm.nih.gov/pubmed/16162254?tool=bestpractice.com[123]Silberstein SD, Armellino JJ, Hoffman HD, et al. Treatment of menstruation-associated migraine with the nonprescription combination of acetaminophen, aspirin, and caffeine: results from three randomized, placebo-controlled studies. Clin Ther. 1999 Mar;21(3):475-91.http://www.ncbi.nlm.nih.gov/pubmed/10321417?tool=bestpractice.com[124]Goldstein J, Hoffman HD, Armellino JJ, et al. Treatment of severe, disabling migraine attacks in an over-the-counter population of migraine sufferers: results from three randomized, placebo-controlled studies of the combination of acetaminophen, aspirin, and caffeine. Cephalalgia. 1999 Sep;19(7):684-91.http://www.ncbi.nlm.nih.gov/pubmed/10524663?tool=bestpractice.com[125]Lipton RB, Stewart WF, Ryan RE Jr, et al. Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain: three double-blind, randomized, placebo-controlled trials. Arch Neurol. 1998 Feb;55(2):210-7.http://archneur.ama-assn.org/cgi/content/full/55/2/210http://www.ncbi.nlm.nih.gov/pubmed/9482363?tool=bestpractice.com
应在患者意识到典型偏头痛发作开始时就立即采取治疗,并且可能需要在发作后期重复治疗。[126]Cady RK, Sheftell F, Lipton RB, et al. Effect of early intervention with sumatriptan on migraine pain: retrospective analyses of data from three clinical trials. Clin Ther. 2000 Sep;22(9):1035-48.http://www.ncbi.nlm.nih.gov/pubmed/11048903?tool=bestpractice.com[127]Cady RK, Lipton RB, Hall C, et al. Treatment of mild headache in disabled migraine sufferers: results of the Spectrum Study. Headache. 2000 Nov-Dec;40(10):792-7.http://www.ncbi.nlm.nih.gov/pubmed/11135022?tool=bestpractice.com[128]Foley KA, Cady R, Martin V, et al. Treating early versus treating mild: timing of migraine prescription medications among patients with diagnosed migraine. Headache. 2005 May;45(5):538-45.http://www.ncbi.nlm.nih.gov/pubmed/15953272?tool=bestpractice.com
如果禁用 NSAID 或曲普坦,或者如果患者怀孕,则可使用扑热息痛。
如果恶心和呕吐是突出症状,则采用止吐剂和经口或肠胃外补液治疗可对患者有益。
通常经由非再呼吸面罩以 15 L/min 速率给予的高流量氧可提供有效的偏头痛急性发作期治疗。[129]Ozkurt B, Cinar O, Cevik E, et al. Efficacy of high-flow oxygen therapy in all types of headache: a prospective, randomized, placebo-controlled trial. Amer J Emerg Med. 2012 Nov;30(9):1760-4.http://www.ncbi.nlm.nih.gov/pubmed/22560101?tool=bestpractice.com
难治性患者的救援药物
如果 NSAID 或曲普坦单用的初始治疗尝试失败,则可使用联合疗法或救援药物。
NSAID 和曲普坦联用可提高急性发作期治疗的效用,且只会轻微增加对患者(对以上单独任何一种药无反应)的副作用。[130]Smith TR, Sunshine A, Stark SR, et al. Sumatriptan and naproxen sodium for the acute treatment of migraine. Headache. 2005 Sep;45(8):983-91.http://www.ncbi.nlm.nih.gov/pubmed/16109111?tool=bestpractice.com[131]Loder E. Fixed drug combinations for the acute treatment of migraine: place in therapy. CNS Drugs. 2005;19(9):769-84.http://www.ncbi.nlm.nih.gov/pubmed/16142992?tool=bestpractice.com[132]Krymchantowski AV, Filho PF, Bigal ME. Rizatriptan vs. rizatriptan plus trimebutine for the acute treatment of migraine: a double-blind, randomized, cross-over, placebo-controlled study. Cephalalgia. 2006 Jul;26(7):871-4.http://www.ncbi.nlm.nih.gov/pubmed/16776704?tool=bestpractice.com[133]Krymchantowski AV, Bigal ME. Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic acid in the acute treatment of migraine. BMC Neurol. 2004 Jun 28;4:10.http://www.biomedcentral.com/1471-2377/4/10http://www.ncbi.nlm.nih.gov/pubmed/15222892?tool=bestpractice.com[134]Krymchantowski AV, Barbosa JS. Rizatriptan combined with rofecoxib vs. rizatriptan for the acute treatment of migraine: an open label pilot study. Cephalalgia. 2002 May;22(4):309-12.http://www.ncbi.nlm.nih.gov/pubmed/12100094?tool=bestpractice.com[135]Peroutka SJ. Beyond monotherapy: rational polytherapy in migraine. Headache. 1998 Jan;38(1):18-22.http://www.ncbi.nlm.nih.gov/pubmed/9504998?tool=bestpractice.com
救援治疗最好为非经口治疗,因为恶心和呕吐是一线治疗失败的常见原因。 在此情况下,止吐剂是应当予以考虑的重要辅助药物。
常用的挽救治疗包括吩噻嗪类药物,因为来自挽救治疗的镇静作用可能比来自一线治疗的镇静作用更容易被接受。[136]Kelly AM, Walcynski T, Gunn B. The relative efficacy of phenothiazines for the treatment of acute migraine: a meta-analysis. Headache. 2009 Oct;49(9):1324-32.http://www.ncbi.nlm.nih.gov/pubmed/19496829?tool=bestpractice.com[137]Bigal ME. Phenothiazines in migraine treatment. Curr Pain Headache Rep. 2010 Aug;14(4):253-5.http://www.ncbi.nlm.nih.gov/pubmed/20490743?tool=bestpractice.com
急诊科成人急性偏头痛的一线治疗应包括静脉给予止吐剂(例如甲氧氯普胺或丙氯拉嗪)[138]Orr SL, Friedman BW, Christie SC, et al. Management of adults with acute migraine in the emergency department: the American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2016 Jun;56(6):911-40.https://onlinelibrary.wiley.com/doi/full/10.1111/head.12835http://www.ncbi.nlm.nih.gov/pubmed/27300483?tool=bestpractice.com联合苯海拉明(以减少静坐不能或肌张力障碍反应的发生率)。[139]Friedman BW, Irizarry E, Solorzano C, et al. Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine. Neurology. 2017 Nov 14;89(20):2075-82.http://www.ncbi.nlm.nih.gov/pubmed/29046364?tool=bestpractice.com异丙嗪也可用于缓解恶心症状。有限的证据表明,该药可能有助于缓解其他偏头痛症状。丙氯拉嗪似乎比异丙嗪起效更快,但在 60 分钟时其结局相似。[110]Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others. Headache. 2012 Feb;52(2):292-306.http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.2011.02070.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22309235?tool=bestpractice.com
美国头痛学会 (American Headache Society, AHS) 指南建议应给予皮下注射舒马曲坦。另外,他们还支持静脉使用酮咯酸、丙戊酸、氟哌啶醇或对乙酰氨基酚。[138]Orr SL, Friedman BW, Christie SC, et al. Management of adults with acute migraine in the emergency department: the American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2016 Jun;56(6):911-40.https://onlinelibrary.wiley.com/doi/full/10.1111/head.12835http://www.ncbi.nlm.nih.gov/pubmed/27300483?tool=bestpractice.com由于存在婴儿/儿童先天畸形和发育问题风险,欧洲和美国均规定妊娠期禁用丙戊酸类药物。[140]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 应避免使用阿片类药物,因为其他治疗方法似乎更有效,而阿片类药物有产生依赖的风险。[138]Orr SL, Friedman BW, Christie SC, et al. Management of adults with acute migraine in the emergency department: the American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2016 Jun;56(6):911-40.https://onlinelibrary.wiley.com/doi/full/10.1111/head.12835http://www.ncbi.nlm.nih.gov/pubmed/27300483?tool=bestpractice.com
静脉补镁可用于先兆偏头痛患者,但对于无先兆偏头痛患者似乎没有任何益处。[138]Orr SL, Friedman BW, Christie SC, et al. Management of adults with acute migraine in the emergency department: the American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2016 Jun;56(6):911-40.https://onlinelibrary.wiley.com/doi/full/10.1111/head.12835http://www.ncbi.nlm.nih.gov/pubmed/27300483?tool=bestpractice.com 当连续使用超过 5-7 天时,经胃肠外补镁可导致发育中的胎儿骨质变薄。这一点是在孕妇接受高剂量该药以预防早产的情况下发现的。[141]US Food and Drug Administration. FDA recommends against prolonged use of magnesium sulfate to stop pre-term labor due to bone changes in exposed babies. May 2013 [internet publication].https://www.fda.gov/downloads/Drugs/DrugSafety/UCM353335.pdf
应提供静脉用皮质类固醇(例如地塞米松),以防止偏头痛复发,但不建议频繁使用,因为可能导致肾上腺功能抑制、骨质疏松、骨坏死或血糖水平升高。不过,如果仅单次使用地塞米松,罕有不可逆副作用(如骨坏死)的报道。[138]Orr SL, Friedman BW, Christie SC, et al. Management of adults with acute migraine in the emergency department: the American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2016 Jun;56(6):911-40.https://onlinelibrary.wiley.com/doi/full/10.1111/head.12835http://www.ncbi.nlm.nih.gov/pubmed/27300483?tool=bestpractice.com
麦角胺和多种麦角衍生物已获批用于偏头痛急性发作期治疗。 专家共识小组的结论是,与麦角胺相比,对于需要偏头痛特异性治疗的大部分患者而言曲普坦是一个更好的选择,因为曲普坦疗效更佳且副作用更少。
可以使用含异丁巴比妥的化合物,但是因为其存在药物滥用和依赖综合征可能性,所以该药物最好仅用于不常受到偏头痛影响的患者。一项针对既往接受过含异丁巴比妥药物有效治疗患者的随机对照临床试验报告,对于偏头痛和相关症状,该药与舒马曲坦与萘普生联用可产生更好的治疗结局。[142]Derosier FS, Sheftell F, Silberstein S, et al. Sumatriptan-naproxen and butalbital: a double-blind, placebo-controlled crossover study. Headache. 2012 Apr;52(4):530-43.http://www.ncbi.nlm.nih.gov/pubmed/22103635?tool=bestpractice.com
对于患有月经性偏头痛的女性,有时会使用经胃肠外补镁。其理论依据是一些偏头痛患者的脑和血清中镁离子水平较低。[143]Kelly AM. Migraine: pharmacotherapy in the emergency department. West J Med. 2000 Sep;173(3):189-93.http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=10986188http://www.ncbi.nlm.nih.gov/pubmed/10986188?tool=bestpractice.com[144]Ramadan NM, Halvorson H, Vande-Linde A, et al. Low brain magnesium in migraine. Headache. 1989 Oct;29(9):590-3.http://www.ncbi.nlm.nih.gov/pubmed/2584000?tool=bestpractice.com[145]Boska MD, Welch KM, Barker PB, et al. Contrasts in cortical magnesium, phospholipid and energy metabolism between migraine syndromes. Neurology. 2002 Apr 23;58(8):1227-33.http://www.ncbi.nlm.nih.gov/pubmed/11971091?tool=bestpractice.com[146]Smeets MC, Vernooy CB, Souverijn JH, et al. Intracellular and plasma magnesium in familial hemiplegic migraine and migraine with and without aura. Cephalalgia. 1994 Feb;14(1):29-32.http://www.ncbi.nlm.nih.gov/pubmed/8200020?tool=bestpractice.com 一项 Meta 分析指出将镁用于偏头痛的紧急治疗存在疑问,但是该分析仅使用了少数研究,且研究终点不尽相同。[147]Choi H, Parmar N. The use of intravenous magnesium sulphate for acute migraine: meta-analysis of randomized controlled trials. Eur J Emerg Med. 2014 Feb;21(1):2-9.http://www.ncbi.nlm.nih.gov/pubmed/23921817?tool=bestpractice.com当连续使用超过 5-7 天时,经胃肠外补镁可导致发育中的胎儿骨质变薄。这一点是在孕妇接受高剂量该药以预防早产的情况下发现的。[141]US Food and Drug Administration. FDA recommends against prolonged use of magnesium sulfate to stop pre-term labor due to bone changes in exposed babies. May 2013 [internet publication].https://www.fda.gov/downloads/Drugs/DrugSafety/UCM353335.pdf
通过标准急诊科偏头痛治疗出院后经口给予司可巴比妥可通过减少头痛和加快头痛症状的消退速度为偏头痛患者提供进一步救援药物治疗。[148]Gerhardt RT, Hermstad E, Crawford DM, et al. Postdischarge secobarbital after ED migraine treatment decreases pain and improves resolution. Am J Emerg Med. 2011 Jan;29(1):86-90.http://www.ncbi.nlm.nih.gov/pubmed/20825791?tool=bestpractice.com
预防治疗
当急性发作期治疗失败或存在禁忌症时,或当发作导致神经系统后遗症时,应考虑对出现致失能性、频繁发作的人进行预防治疗。[149]Freitag FG, Collins SD, Carlson HA, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology. 2002 Jun 11;58(11):1652-9.http://www.ncbi.nlm.nih.gov/pubmed/12058094?tool=bestpractice.com[150]Silberstein SD, Collins SD. Safety of divalproex sodium in migraine prophylaxis: an open-label, long-term study. Long-term Safety of Depakote in Headache Prophylaxis Study Group. Headache. 1999 Oct;39(9):633-43.http://www.ncbi.nlm.nih.gov/pubmed/11284461?tool=bestpractice.com[151]Silberstein SD, Wilmore LJ. Divalproex sodium: migraine treatment and monitoring. Headache. 1996 Apr;36(4):239-42.http://www.ncbi.nlm.nih.gov/pubmed/8675429?tool=bestpractice.com[152]Mathew NT, Saper JR, Silberstein SD, et al. Migraine prophylaxis with divalproex. Arch Neurol. 1995 Mar;52(3):281-6.http://www.ncbi.nlm.nih.gov/pubmed/7872882?tool=bestpractice.com[153]Joffe H, Cohen LS, Suppes T, et al. Longitudinal follow-up of reproductive and metabolic features of valproate-associated polycystic ovarian syndrome features: a preliminary report. Biol Psychiatry. 2006 Dec 15;60(12):1378-81.http://www.ncbi.nlm.nih.gov/pubmed/16950230?tool=bestpractice.com
专家建议,偏头痛预防治疗的选择应基于经证实的疗效、患者偏好和头痛特征、药物副作用以及是否存在怀孕等共存或并存状况。
应以较低剂量开始治疗,并且在适当的试验阶段后进行重新评估。[154]Silberstein SD, Lipton RB, Goadsby PJ. Headache in clinical practice. 2nd ed. Oxford: Martin Dunitz; 2002. 有几种非药物治疗对偏头痛预防有效,包括生物反馈辅助的放松以及认知行为疗法。 这些疗法尤其适用于已怀孕或试图怀孕的女性、儿童或者想要避免或无法耐受药物疗法的其他人。[155]Pryse-Phillips WE, Dodick DW, Edmeads JG, et al. Guidelines for the nonpharmacologic management of migraine in clinical practice. Canadian Headache Society. CMAJ. 1998 Jul 14;159(1):47-54.http://www.cmaj.ca/cgi/reprint/159/1/47http://www.ncbi.nlm.nih.gov/pubmed/9679487?tool=bestpractice.com[156]Holroyd KA, Penzien DB. Psychosocial interventions in the management of recurrent headache disorders. 1: Overview and effectiveness. Behav Med. 1994 Summer;20(2):53-63.http://www.ncbi.nlm.nih.gov/pubmed/7803937?tool=bestpractice.com[157]Marcus DA, Scharff L, Turk DC. Nonpharmacological management of headaches during pregnancy. Psychosom Med. 1995 Nov-Dec;57(6):527-35.http://www.ncbi.nlm.nih.gov/pubmed/8600478?tool=bestpractice.com 睡眠不足、压力、抑郁、焦虑以及过量服药均为对药物预防无反应的危险因素。进行非药物治疗或专家咨询来解决这些问题可能会改善结局。[158]Probyn K, Bowers H, Caldwell F, et al. Prognostic factors for chronic headache: a systematic review. Neurology. 2017 Jul;89(3): 291-301.http://n.neurology.org/content/89/3/291.longhttp://www.ncbi.nlm.nih.gov/pubmed/28615422?tool=bestpractice.com
预防治疗的最佳持续时间尚不清楚。 如果发现有效的疗法,大多数专家建议持续时间至少为 4 至 6 个月。 到那时,可在几周或几个月内缓慢降低剂量,同时监测头痛频率的任何变化并且在必要时重新开始全剂量治疗。 一些患有致失能性极高或极为棘手的头痛的患者倾向于无限期地继续接受预防治疗。[159]Evans RW, Loder E, Biondi DM. When can successful migraine prophylaxis be discontinued? Headache. 2004 Nov-Dec;44(10):1040-2.http://www.ncbi.nlm.nih.gov/pubmed/15546270?tool=bestpractice.com 但是,对预防治疗的耐受性可能会限制这些疗法的有效性。[160]Rizzoli P, Loder EW. Tolerance to the beneficial effects of prophylactic migraine drugs: a systematic review of causes and mechanisms. Headache. 2011 Sep;51(8):1323-35.http://www.ncbi.nlm.nih.gov/pubmed/21884087?tool=bestpractice.com
如果在医学上适当,应考虑对有月经性偏头痛的女性进行激素治疗,以抑制月经。然而,含雌激素的产品有引发血栓栓塞事件的风险。有先兆偏头痛的女性在使用复方激素避孕药时,发生脑血管事件的风险增加,[161]Sacco S, Merki-Feld GS, Ægidius KL, et al. Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC). J Headache Pain. 2017 Oct 30;18(1):108.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662520/http://www.ncbi.nlm.nih.gov/pubmed/29086160?tool=bestpractice.com 因此应使用其他药物治疗偏头痛,而不是对月经周期进行控制。有证据表明曲普坦类药物(尤其是夫罗曲坦 [frovatriptan]、佐米曲普坦、那拉曲坦 [naratriptan])可能有助于短期预防月经性偏头痛。[162]Maasumi K, Tepper SJ, Kriegler JS. Menstrual migraine and treatment options: review. Headache. 2017 Feb;57(2):194-208.https://onlinelibrary.wiley.com/doi/full/10.1111/head.12978http://www.ncbi.nlm.nih.gov/pubmed/27910087?tool=bestpractice.com
对于孕妇,当连续使用超过 5-7 天时,经胃肠外补镁可导致发育中的胎儿骨质变薄。这一点是在孕妇接受高剂量该药以预防早产的情况下发现的。[141]US Food and Drug Administration. FDA recommends against prolonged use of magnesium sulfate to stop pre-term labor due to bone changes in exposed babies. May 2013 [internet publication].https://www.fda.gov/downloads/Drugs/DrugSafety/UCM353335.pdf AHS 指出,由于不知道此类骨质异常可能发生在什么剂量下,也不知道是否会在口服镁剂时发生,所以不再推荐将镁作为妊娠期的日常预防性药物。[163]Tepper D. Pregnancy and lactation - migraine management. Headache. 2015 Apr;55(4):607-8.https://americanheadachesociety.org/wp-content/uploads/2018/05/Pregnancy_and_Lactation_Toolbox.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/25881682?tool=bestpractice.com
用于偏头痛预防的主要药物包括抗惊厥药(丙戊酸和托吡酯[58]Evers S, Jensen R, European Federation of Neurological Societies. Treatment of medication overuse headache - guideline of the EFNS headache panel. Eur J Neurol. 2011 Sep;18(9):1115-21.http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2011.03497.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21834901?tool=bestpractice.com)、 [
]Can topiramate help to prevent episodic migraine in adults?https://cochranelibrary.com/cca/doi/10.1002/cca.1481/full显示答案 三环类抗抑郁药和 β 受体阻断剂。2018 年,欧洲药品管理局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预防偏头痛,因为存在胎儿/儿童出现先天畸形和发育问题的风险。[140]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,禁止对孕妇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物不得用于存在生育可能性的女性患者。[140]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 对于慢性偏头痛和药物过度使用性头痛患者的预防治疗,唯一具有中级证据的药物为托吡酯。[58]Evers S, Jensen R, European Federation of Neurological Societies. Treatment of medication overuse headache - guideline of the EFNS headache panel. Eur J Neurol. 2011 Sep;18(9):1115-21.http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2011.03497.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21834901?tool=bestpractice.com [
]Can topiramate help to prevent episodic migraine in adults?https://cochranelibrary.com/cca/doi/10.1002/cca.1481/full显示答案
如果患者同时有抑郁,那么首选药物为文拉法辛或选择性 5-羟色胺再摄取抑制剂。常用于治疗神经病变和纤维肌痛的较新抗抑郁剂(例如度洛西汀)已用于头痛治疗,但是仅有一项开放标签试验进行报道。[164]Volpe FM. An 8-week, open-label trial of duloxetine for comorbid major depressive disorder and chronic headache. J Clin Psychiatry. 2008 Sep;69(9):1449-54.http://www.ncbi.nlm.nih.gov/pubmed/19193344?tool=bestpractice.com
钙离子通道阻滞剂是偏瘫性偏头痛(偏头痛伴运动无力等先兆)和有脑干先兆的偏头痛(伴来源于脑干但无运动无力先兆症状的偏头痛)患者的首选药物,并且被广泛用于治疗有先兆偏头痛。[165]Lastimosa AC. Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil. Neurology. 2003 Sep 9;61(5):721-2.http://www.ncbi.nlm.nih.gov/pubmed/12963781?tool=bestpractice.com[166]Yu W, Horowitz SH. Familial hemiplegic migraine and its abortive therapy with intravenous verapamil. Neurology. 2001 Nov 13;57(9):1732-3.http://www.ncbi.nlm.nih.gov/pubmed/11706128?tool=bestpractice.com[167]Greenberg DA. Calcium channel antagonists and the treatment of migraine. Clin Neuropharmacol. 1986;9(4):311-28.http://www.ncbi.nlm.nih.gov/pubmed/2425960?tool=bestpractice.com
已发现与安慰剂相比当将肉毒杆菌毒素 A 型注入眉间、额肌和颞肌时可减少偏头痛发作。[168]Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010 Jul;30(7):793-803.http://www.ncbi.nlm.nih.gov/pubmed/20647170?tool=bestpractice.com[169]Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010 Jul;30(7):804-14.http://www.ncbi.nlm.nih.gov/pubmed/20647171?tool=bestpractice.com[170]Aurora SK, Winner P, Freeman MC, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program. Headache. 2011 Oct;51(9):1358-73.http://www.ncbi.nlm.nih.gov/pubmed/21883197?tool=bestpractice.com[171]Jackson JL, Kuriyama A, Hayashino Y. Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis. JAMA. 2012 Apr 25;307(16):1736-45.http://www.ncbi.nlm.nih.gov/pubmed/22535858?tool=bestpractice.com[172]National Institute for Health and Care Excellence. Botulinum toxin type A for the prevention of headaches in adults with chronic migraine. June 2012 [internet publication].http://www.nice.org.uk/guidance/TA260 [
]How does botulinum toxin type A compare with placebo for preventing migraine in adults?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2241/full显示答案已显示使用肉毒杆菌毒素 A 治疗慢性偏头痛可减少头痛影响并提高生活质量。[173]Lipton RB, Varon SF, Grosberg B, et al. OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine. Neurology. 2011 Oct 11;77(15):1465-72.http://www.ncbi.nlm.nih.gov/pubmed/21956721?tool=bestpractice.com
降钙素基因相关肽 (CGRP) 抑制剂
CGRP 抑制剂是预防偏头痛的一种新型疗法。这类药物工作原理是抑制 CGRP 受体。有研究认为 CGRP 与偏头痛的病理生理学之间有着因果关系。
Erenumab:是首个具有选择性 CGRP 拮抗活性的人类单克隆抗体。该药被批准用于每个月有>4 次头痛发作人群的偏头痛预防,每月一次自我皮下注射给药。在两项分别涉及 667 名慢性偏头痛患者和 955 名发作性偏头痛患者的临床试验中,经过 3 个月治疗后,与安慰剂相比,使用 Erenumab 的慢性偏头痛患者每月的偏头痛天数平均减少 2.5 天。对于发作性偏头痛患者,根据所服剂量不同,分别减少 1.3 或 1.8 天。最常见的副作用包括注射部位反应、便秘、肌痉挛和瘙痒。[174]Dodick DW, Ashina M, Brandes JL, et al. ARISE: a phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018 May;38(6):1026-37.http://www.ncbi.nlm.nih.gov/pubmed/29471679?tool=bestpractice.com[175]Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jun;16(6):425-34.https://www.sciencedirect.com/science/article/pii/S1474442217300832?via%3Dihubhttp://www.ncbi.nlm.nih.gov/pubmed/28460892?tool=bestpractice.com
Fremanezumab:自我皮下注射,每月一次或每 3 月一次。美国食品药品监督管理局 (FDA) 批准其用于预防发作性偏头痛。在两项分别涉及 1130 名慢性偏头痛患者和 875 名发作性偏头痛患者的临床试验中,经过 3 个月治疗后,与安慰剂相比,使用 Fremanezumab 的慢性偏头痛患者每月的偏头痛天数平均分别减少 2.1 天(每月给药)或 1.8 天(每季度给药)。对于发作性偏头痛患者,每月给药或每季度给药的患者分别减少 1.5 或 1.3 天。最常见的副作用是注射部位反应。[176]Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017 Nov 30;377(22):2113-22.https://www.nejm.org/doi/full/10.1056/NEJMoa1709038http://www.ncbi.nlm.nih.gov/pubmed/29171818?tool=bestpractice.com[177]Dodick DW, Silberstein SD, Bigal ME, et al. Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial. JAMA. 2018 May 15;319(19):1999-2008.http://www.ncbi.nlm.nih.gov/pubmed/29800211?tool=bestpractice.com
Galcanezumab:皮下注射,每月一次。FDA 批准其用于预防发作性偏头痛。在两项包括超过 1700 名发作性偏头痛患者的临床试验中,经过 6 个月的治疗后,与安慰剂相比,使用 Galcanezumab 的患者每月偏头痛天数平均减少 1.9 天(低剂量)和 1.8 天(大剂量)。最常见的副作用是注射部位反应。[178]Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 2018 Sep 1;75(9):1080-8.https://jamanetwork.com/journals/jamaneurology/fullarticle/2681442http://www.ncbi.nlm.nih.gov/pubmed/29813147?tool=bestpractice.com[179]Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia. 2018 Jul;38(8):1442-54.http://www.ncbi.nlm.nih.gov/pubmed/29848108?tool=bestpractice.com
尚无足够的证据支持推荐或反对采用物理疗法治疗偏头痛。几项系统评价得出的结论为:现有研究的质量太低,不足以证明常规使用该治疗是合理的。[180]Biondi DM. Physical treatments for headache: a structured review. Headache. 2005 Jun;45(6):738-46.http://www.ncbi.nlm.nih.gov/pubmed/15953306?tool=bestpractice.com[181]Chaibi AT, Tuchin PJ, Russell MB. Manual therapies for migraine: a systematic review. J Headache Pain. 2011 Apr;12(2):127-33.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072494/http://www.ncbi.nlm.nih.gov/pubmed/21298314?tool=bestpractice.com
关于针灸的证据存在矛盾。[182]Griggs C, Jensen J. Effectiveness of acupuncture for migraine: critical literature review. J Adv Nurs. 2006 May;54(4):491-501.http://www.ncbi.nlm.nih.gov/pubmed/16671978?tool=bestpractice.com 一项系统评价报告称,在头痛发作的对症治疗中增加针灸减少了头痛频率;但是,与预防性药物治疗相比,这种效果在随访(3 个月)时未得以维持。[183]Linde K, Allais G, Brinkhaus B, et al. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev. 2016 Jun 28;(6):CD001218.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001218.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27351677?tool=bestpractice.com 另一项系统评价报告称,针灸治疗慢性偏头痛的效果优于常规治疗和伪针灸治疗;但相对于伪针灸治疗,针灸治疗的效果增加幅度较小。 [184]MacPherson H, Vickers A, Bland M, et al. Acupuncture for chronic pain and depression in primary care: a programme of research. Southampton (UK): NIHR Journals Library; 2017 Jan.https://www.ncbi.nlm.nih.gov/books/NBK409491/http://www.ncbi.nlm.nih.gov/pubmed/28121095?tool=bestpractice.com 鉴于证据的质量,目前尚无法就针灸在偏头痛预防性治疗方面的使用给出支持或反对的建议。
尚无证据显示脊柱推拿术可有效治疗偏头痛。[185]Posadzki PE, Ernst E. Spinal manipulations for the treatment of migraine: a systematic review of randomized clinical trials. Cephalalgia. 2011 Jun;31(8):964-70.http://www.ncbi.nlm.nih.gov/pubmed/21511952?tool=bestpractice.com
外周静脉置管的动画演示
手术
还没有充分的证据可推荐使用外科疗法治疗偏头痛。[187]Ambrosini A, Schoenen J. Invasive pericranial nerve interventions. Cephalalgia, 2016 Oct;36(12): 1156-69.http://journals.sagepub.com/doi/pdf/10.1177/0333102416639515http://www.ncbi.nlm.nih.gov/pubmed/27009564?tool=bestpractice.com