今日の臨床サポート 今日の臨床サポート

著者: 竹島多賀夫 社会医療法人寿会富永病院

監修: 高橋裕秀 昭和大学藤が丘病院 脳神経内科

著者校正/監修レビュー済:2025/04/23
参考ガイドライン:
  1. 日本頭痛学会日本神経学会:頭痛の診療ガイドライン2021
患者向け説明資料

改訂のポイント:
  1. 定期レビューを行い、下記の点を加筆・修正した。
  1. CGRP関連抗体薬(ガルカネズマブ、エレヌマブ、フレマネズマブ)のエビデンスと使用法について記載した。
  1. ジタン系片頭痛急性期治療薬ラスミジタンについて記載した。

概要・推奨   

  1. 頭痛の分類と診断は、国際頭痛分類第3版International Classification of Headache Disorders 3rd Edition(ICHD-3)に準拠して診断する(推奨度1)
  1. 「人生最悪の頭痛」「これまでに経験のない頭痛」は、緊急性の高い二次性頭痛の可能性を念頭において、十分検索する必要がある(推奨度1)
  1. 片頭痛発作期急性期の特異的治療薬として、トリプタンが有効である(推奨度1)
アカウントをお持ちの方はログイン
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧 にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり

病態・疫学・診察 

疫学情報・病態・注意事項  
ポイント:
  1. 頭痛(英語:headache、cephalalgia)とは、頭部の一部あるいは全体の痛みの総称であり、後頭部と後頚部の境界、眼の奥の痛みも頭痛として扱う。頭皮の外傷や感染などによって生じる頭の一部の表面の痛みは通常は頭痛とはいわない。
  1. 頭痛は、熱や腹痛と同様に症状名であるが、慢性的に頭痛発作を繰り返す場合に、疾病(頭痛症)として取り扱う。
  1. 頭痛を来す原因疾患には、明白な器質的異常との関連がみられない一次性頭痛疾患と器質的異常によって頭痛が引き起こされている二次性頭痛疾患が存在する。
  1. 頭痛の診断は国際頭痛分類第3版の診断基準(ICHD-3)に沿って行う。ICHD-3は階層的な頭痛分類がなされている。プライマリケアでは、ICHD-3の頭痛グループ(2桁でコードされるレベル)、すなわち、片頭痛、緊張型頭痛、群発頭痛のレベルで診断できることが求められる。神経内科専門医、頭痛専門医は3桁のレベル、すなわち「1.2.1典型的前兆に片頭痛を伴うもの」、「1.2.2脳幹性前兆を伴う片頭痛」などの診断ができる必要がある。
  1. なお、頭痛のない頭痛性疾患も存在する。頭痛の訴えがなくとも頭痛性疾患の可能性を考慮して除外診断が必要なことがある。例えば、閃輝暗点のみで頭痛を伴わないものは、前兆のある片頭痛のサブタイプに診断される。また、小児周期性嘔吐症、腹部片頭痛、小児両性発作性めまいは、頭痛がなくとも片頭痛のサブタイプに分類される。また、脳底型片頭痛の一部では、意識障害が高度で患者は頭痛を訴えないこともある。
問診・診察のポイント  
 
問診:
  1. 頭痛の性状、部位、程度、持続時間、随伴症状(悪心、嘔吐、光過敏、音過敏、流涙、眼充血、鼻汁漏、鼻閉、眼瞼浮腫、眼瞼下垂)、前兆(閃輝暗点、感覚障害、言語障害、運動麻痺、めまい、失調など)について問診する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

日本頭痛学会・国際頭痛分類委員会訳. 国際頭痛分類第3版(ICHD-3) [Internet]. 医学書院; 2018. Available from: http://www.jhsnet.org/kokusai_new_2019.html
Mayer PL, Awad IA, Todor R, Harbaugh K, Varnavas G, Lansen TA, Dickey P, Harbaugh R, Hopkins LN.
Misdiagnosis of symptomatic cerebral aneurysm. Prevalence and correlation with outcome at four institutions.
Stroke. 1996 Sep;27(9):1558-63. doi: 10.1161/01.str.27.9.1558.
Abstract/Text BACKGROUND AND PURPOSE: It is not known what fraction of patients with symptomatic cerebral aneurysms are misdiagnosed at initial medical presentation. It is also not clear whether misdiagnosed patients more frequently deteriorate before definitive aneurysm diagnosis and therapy or achieve a poorer outcome than correctly diagnosed patients.
METHODS: We reviewed records of consecutive patients with symptomatic cerebral aneurysms managed by four tertiary-care neurosurgical services during a recent 19-month period. Clinical course and outcome were analyzed according to misdiagnosis or correct diagnosis at initial medical evaluation.
RESULTS: Fifty-four of 217 patients (25%) were misdiagnosed at initial medical evaluation, including 46 of 121 patients (38%) initially in good clinical condition (clinical grade 1 or 2). Forty-six of 54 patients (85%) in the misdiagnosis group were initially grade 1 or 2 compared with 75 of 163 patients (46%) with correct initial diagnosis (P < .01). Twenty-six of 54 misdiagnosed patients (48%) deteriorated or rebled before definitive aneurysm treatment compared with 4 of 165 correctly diagnosed patients (2%) (P < .001). Among patients initially presenting as clinical grade 1 or 2, overall good or excellent outcome was achieved in 91% of those with correct initial diagnosis and 53% of patients with initial misdiagnosis (P < .001). Deterioration before correct diagnosis accounted for 16 of 67 patients (24%) with poor or worse final outcome in this series.
CONCLUSIONS: Patients in good clinical condition with symptomatic cerebral aneurysms were commonly misdiagnosed. Misdiagnosed patients were more likely than correctly diagnosed patients to deteriorate clinically and had a worse overall outcome. Misdiagnosed cases accounted for a significant fraction of overall poor outcomes among consecutive cases of symptomatic aneurysms.

PMID 8784130
日本頭痛学会・国際頭痛分類普及委員会訳:国際頭痛分類第3版beta版.医学書院, 2014.
Bigal ME, Lipton RB.
Concepts and mechanisms of migraine chronification.
Headache. 2008 Jan;48(1):7-15. doi: 10.1111/j.1526-4610.2007.00969.x.
Abstract/Text Migraine is a chronic recurrent disorder with episodic manifestations that is progressive in some individuals. Migraine progresses clinically, physiologically, and anatomically. Progression may be a consequence of the mechanisms that generate the migraine attacks (eg, cortical spreading depression) or it may be a function of the activations generated by the attacks (eg, lesions in the periaqueductal gray area), a hypothesis supported by the increase in lesions with attack frequency. Progression may also be partially explained by common genetic or environmental risk factors. Finally, migraine with aura is associated with an elevated Framingham score and with risk factors for cardiovascular disease. Research on this issue is in its infancy and cautions are necessary before extrapolating this information into clinical practice.

PMID 18184280
Lyngberg AC, Rasmussen BK, Jørgensen T, Jensen R.
Prognosis of migraine and tension-type headache: a population-based follow-up study.
Neurology. 2005 Aug 23;65(4):580-5. doi: 10.1212/01.wnl.0000172918.74999.8a.
Abstract/Text OBJECTIVE: To determine the prognosis of migraine and tension-type headache and to identify prognostic factors.
METHODS: Of 740 persons (aged 25 to 64 years) examined in a 1989 Danish cross-sectional headache study, 673 were eligible for follow-up in 2001. All interviews at baseline and at follow-up were conducted by medical doctors and based on the 1988 IHS-criteria.
RESULTS: A total of 549 persons (81.6%) participated in the follow-up study. Of 64 migraineurs at baseline, 42% had experienced remission, 38% had low migraine frequency, and 20% had more than 14 migraine days per year (poor outcome) at follow-up. Poor outcome was associated with high migraine frequency at baseline and age at onset younger than 20 years. Among 146 subjects with frequent episodic tension-type headache and 15 with chronic tension-type headache at baseline, 45% experienced infrequent or no tension-type headache (remission), 39% had frequent episodic tension-type headache, and 16% experienced chronic tension-type headache (poor outcome) at follow-up. Poor outcome was associated with baseline chronic tension-type headache, coexisting migraine, not being married, and sleeping problems.
CONCLUSIONS: The prognosis of migraine, frequent episodic tension-type headache, and chronic tension-type headache was favorable.

PMID 16116119
Kinze S, Clauss M, Reuter U, Wolf T, Dreier JP, Einhäupl KM, Arnold G.
Valproic acid is effective in migraine prophylaxis at low serum levels: a prospective open-label study.
Headache. 2001 Sep;41(8):774-8. doi: 10.1046/j.1526-4610.2001.01142.x.
Abstract/Text OBJECTIVE: We evaluated the efficacy of prophylactic valproic acid treatment (6 months) on the frequency of migraine attacks and the number of migraine headache days with respect to serum levels.
BACKGROUND: Valproic acid, a GABAergic drug, has been shown to be effective for migraine prophylaxis. Results from several dose- and serum level-adjusted studies have recommended valproic acid doses within a range of 500 to 1500 mg per day for migraine prophylaxis.
DESIGN AND METHODS: In this prospective open-label study, 52 patients received valproic acid doses of 300 to 1200 mg per day; 45 patients were treated per protocol. Valproic acid serum levels increased linearly in relation to the valproic acid dose and were between 21 and 107 microg/mL at the end of the treatment period. Patients were divided into two groups: those with valproic acid serum levels less than 50 microg/mL (group 1) and those with serum levels greater than 50 microg/mL (group 2).
RESULTS: The frequency of migraine attacks was significantly reduced in group 1 from 3.5 +/- 0.9 to 2.0 +/- 0.9 attacks per month. Migraine headache days also decreased (6.4 +/- 3.5 to 4.6 +/- 2.9 days per month). In the high serum level group, a reduction of migraine attacks from 3.5 +/- 0.9 to 2.8 +/- 1.0 attacks per month and only a slight decrease in headache days (6.4 +/- 3.5 to 6.1 +/- 2.4 days per month) was observed. The outcome of group 1 (low serum level) was significantly better than that of group 2 with respect to both parameters (P<.05). Side effects were generally mild and temporary.
CONCLUSIONS: Due to the lack of additional benefit from higher valproic acid doses (more than 600 mg per day), we recommend daily valproic acid doses of 500 to 600 mg with a target serum level less than 50 microg/mL for the prophylactic treatment of migraine.

PMID 11576201
Ghose K, Niven B.
Prophylactic sodium valproate therapy in patients with drug-resistant migraine.
Methods Find Exp Clin Pharmacol. 1998 May;20(4):353-9. doi: 10.1358/mf.1998.20.4.485692.
Abstract/Text We assessed the efficacy of sodium valproate as a prophylactic agent in migraine headache. A prospective randomized study was conducted in adult patients who previously derived no significant benefit from most conventional prophylactic therapy for migraine. Twenty-seven patients with a diagnosis of migraine with aura or migraine without aura from a headache clinic received low dose sodium valproate for 3 months. Response to therapy was defined as 50% or greater reduction in the frequency of headache. Plasma drug level monitoring helped to identify four noncompliers who were excluded from the study. Seventeen (71%) patients observed improvement within 4-6 weeks of medication and remained well for 12 weeks. They were further followed up for 12-24 months. Two patients for side effects and 1 for nondrug-related problems were withdrawn from follow-up study. Twelve patients (60%) maintained their response for 12 months or longer. Clinical improvement (percentage reduction in the frequency of migraine attacks) correlated inversely with the plasma drug levels at 13-24 months and daily dose of valproate, among the responders, suggestive of a possible therapeutic window. In other words, patients who do not respond to low dose valproate are unlikely to benefit from further increase in dosage.

PMID 9658386
Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK, de Jong-van den Berg LT; EUROCAT Antiepileptic Study Working Group.
Valproic acid monotherapy in pregnancy and major congenital malformations.
N Engl J Med. 2010 Jun 10;362(23):2185-93. doi: 10.1056/NEJMoa0907328.
Abstract/Text BACKGROUND: The use of valproic acid in the first trimester of pregnancy is associated with an increased risk of spina bifida, but data on the risks of other congenital malformations are limited.
METHODS: We first combined data from eight published cohort studies (1565 pregnancies in which the women were exposed to valproic acid, among which 118 major malformations were observed) and identified 14 malformations that were significantly more common among the offspring of women who had received valproic acid during the first trimester. We then assessed the associations between use of valproic acid during the first trimester and these 14 malformations by performing a case-control study with the use of the European Surveillance of Congenital Anomalies (EUROCAT) antiepileptic-study database, which is derived from population-based congenital-anomaly registries. Registrations (i.e., pregnancy outcomes with malformations included in EUROCAT) with any of these 14 malformations were compared with two control groups, one consisting of infants with malformations not previously linked to valproic acid use (control group 1), and one consisting of infants with chromosomal abnormalities (control group 2). The data set included 98,075 live births, stillbirths, or terminations with malformations among 3.8 million births in 14 European countries from 1995 through 2005.
RESULTS: Exposure to valproic acid monotherapy was recorded for a total of 180 registrations, with 122 registrations in the case group, 45 in control group 1, and 13 in control group 2. As compared with no use of an antiepileptic drug during the first trimester (control group 1), use of valproic acid monotherapy was associated with significantly increased risks for 6 of the 14 malformations under consideration; the adjusted odds ratios were as follows: spina bifida, 12.7 (95% confidence interval [CI], 7.7 to 20.7); atrial septal defect, 2.5 (95% CI, 1.4 to 4.4); cleft palate, 5.2 (95% CI, 2.8 to 9.9); hypospadias, 4.8 (95% CI, 2.9 to 8.1); polydactyly, 2.2 (95% CI, 1.0 to 4.5); and craniosynostosis, 6.8 (95% CI, 1.8 to 18.8). Results for exposure to valproic acid were similar to results for exposure to other antiepileptic drugs.
CONCLUSIONS: The use of valproic acid monotherapy in the first trimester was associated with significantly increased risks of several congenital malformations, as compared with no use of antiepileptic drugs or with use of other antiepileptic drugs.

Copyright 2010 Massachusetts Medical Society.
PMID 20558369
Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J, Conley RR.
Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial.
JAMA Neurol. 2018 Sep 1;75(9):1080-1088. doi: 10.1001/jamaneurol.2018.1212.
Abstract/Text IMPORTANCE: Migraine is a disabling neurological disease characterized by severe headache attacks. Treatment options reduce migraine frequency for many patients, but adverse effects lead to discontinuation in many patients.
OBJECTIVE: To demonstrate that galcanezumab is superior to placebo in the prevention of episodic migraine with or without aura.
DESIGN, SETTING, AND PARTICIPANTS: The EVOLVE-1 (Evaluation of LY2951742 in the Prevention of Episodic Migraine 1) trial was a double-blind, randomized, placebo-controlled (January 11, 2016, to March 22, 2017) trial comparing galcanezumab (120 mg and 240 mg) vs placebo. Patients received treatments once monthly for 6 months (subcutaneous injection via prefilled syringe) and were followed up for 5 months after their last injection. It was a multicenter, clinic-based study involving 90 sites in North America. Participants in the study were adults (aged 18 to 65 years) with at least a 1-year history of migraine, 4 to 14 migraine headache days per month and a mean of at least 2 migraine attacks per month within the past 3 months, and were diagnosed prior to age 50 years. During the study, no other preventive medications were allowed. A total of 1671 patients were assessed; 809 did not meet study entry or baseline criteria, and 858 were included in the intent-to-treat population.
INTERVENTIONS: Patients were randomized (2:1:1) to monthly placebo, galcanezumab, 120 mg, and galcanezumab, 240 mg.
MAIN OUTCOMES AND MEASURES: The primary outcome was overall mean change from baseline in the number of monthly migraine headache days during the treatment period. Secondary measures included at least 50%, at least 75%, and 100% reduction in monthly migraine headache days, migraine headache days with acute medication use, and scores from the Migraine-Specific Quality of Life questionnaire, Patient Global Impression of Severity, and Migraine Disability Assessment. Treatment-emergent adverse events and serious adverse events were reported.
RESULTS: Of the 1671 patients assessed, 858 (mean age, 40.7 years; 718 women [83.7%]) met study entry criteria and received at least 1 dose of investigational product. The primary objective was met for both galcanezumab doses; treatment with galcanezumab significantly reduced monthly migraine headache days (both P < .001) by 4.7 days (120 mg) and 4.6 days (240 mg) compared with placebo (2.8 days). All key secondary objectives were also significant after multiplicity adjustment. There were no meaningful differences between 120-mg and 240-mg doses of galcanezumab on measures of efficacy. Completion rate during treatment was high (81.9%; n = 718), and the incidence of discontinuation owing to adverse events was less than 5% across all treatment groups.
CONCLUSIONS AND RELEVANCE: Galcanezumab 120-mg and 240-mg monthly injections provided clinical benefits and improved functioning. The incidence rate of adverse events was low, demonstrating the favorable tolerability profile of galcanezumab.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02614183.

PMID 29813147
Detke HC, Millen BA, Zhang Q, Samaan K, Ailani J, Dodick DW, Aurora SK.
Rapid Onset of Effect of Galcanezumab for the Prevention of Episodic Migraine: Analysis of the EVOLVE Studies.
Headache. 2020 Feb;60(2):348-359. doi: 10.1111/head.13691. Epub 2019 Nov 11.
Abstract/Text OBJECTIVE: To evaluate onset of effect of galcanezumab in patients with episodic migraine.
BACKGROUND: Galcanezumab is a monoclonal antibody that binds to calcitonin gene-related peptide and is indicated for preventive treatment of migraine.
DESIGN/METHODS: Data on the primary outcome measure were analyzed from 2 previously published double-blind, Phase 3 studies (EVOLVE-1 [N = 858] and EVOLVE-2 [N = 915]) wherein adult patients with episodic migraine were randomized to receive monthly subcutaneous injections of galcanezumab 120 mg (with 240-mg loading dose) or 240 mg or placebo for up to 6 months. Monthly onset of effect was defined as the earliest month at which galcanezumab achieved and subsequently maintained statistical superiority to placebo on the mean change from baseline in the number of monthly migraine headache days (MHDs). If onset occurred in Month 1, weekly onset was evaluated and defined as the earliest week at which galcanezumab statistically separated from placebo and maintained statistical separation for remaining weeks in that month. Day of onset of effect was also analyzed, as were monthly and weekly onset, for occurrence of ≥50% reduction from baseline in number of MHDs.
RESULTS: For both studies, change from baseline in monthly MHDs showed a statistically significant separation of galcanezumab from placebo at Month 1 and each subsequent month (each P < .001). Analysis of the first month for both studies indicated onset of effect in the first week, with galcanezumab-treated patients having significantly higher odds of having fewer MHDs in the first week (odds ratio [95% confidence interval] for EVOLVE-1, 2.71 [2.00, 3.66], and for EVOLVE-2, 2.88 [2.16, 3.86]; both P < .001) and each subsequent week compared with placebo-treated patients (P ≤ .004). Daily analysis showed onset of effect at Day 1 (first day after injection day). Galcanezumab also demonstrated superiority to placebo on occurrence of ≥50% reduction in MHDs starting at Week 1 (percentage of patients with 50% response in galcanezumab group vs placebo group for EVOLVE-1, 54.3% vs 32.4% [P < .001], and for EVOLVE-2, 59.4% vs 38.0% [P < .001]).
CONCLUSION: Rapid onset of preventive effect on the first day after injection of galcanezumab was confirmed in both studies of episodic migraine.

© 2019 Eli Lilly and Company. Headache: The Journal of Head and Face Pain published by Wiley Periodicals, Inc.
PMID 31710104
Detke HC, Goadsby PJ, Wang S, Friedman DI, Selzler KJ, Aurora SK.
Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study.
Neurology. 2018 Dec 11;91(24):e2211-e2221. doi: 10.1212/WNL.0000000000006640. Epub 2018 Nov 16.
Abstract/Text OBJECTIVE: To evaluate the efficacy and safety of galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, in the preventive treatment of chronic migraine.
METHODS: A phase 3, randomized, double-blind, placebo-controlled study of LY2951742 in patients with chronic migraine (Evaluation of Galcanezumab in the Prevention of Chronic Migraine [REGAIN]) was a phase 3 study with a 3-month double-blind, placebo-controlled treatment phase and a 9-month open-label extension. Eligible patients 18 to 65 years of age with chronic migraine were randomized 2:1:1 to monthly subcutaneous injections of placebo (n = 558), galcanezumab 120 mg (with a 240-mg loading dose, n = 278), or galcanezumab 240 mg (n = 277). The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days (MHDs) during the 3-month double-blind treatment phase.
RESULTS: Mean number of monthly MHDs at baseline was 19.4 for the total sample. Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo -2.7, galcanezumab 120 mg -4.8, galcanezumab 240 mg -4.6) (p < 0.001 for each dose compared to placebo). There were no clinically meaningful differences between galcanezumab doses and placebo on any safety or tolerability outcome except for a higher incidence of treatment-emergent injection-site reaction (p < 0.01), injection-site erythema (p < 0.001), injection-site pruritus (p < 0.01), and sinusitis (p < 0.05) in the galcanezumab 240-mg group relative to placebo.
CONCLUSIONS: Both doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs. Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.
CLINICALTRIALSGOV IDENTIFIER: NCT02614261.
CLASSIFICATION OF EVIDENCE: This interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.

Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PMID 30446596
Förderreuther S, Zhang Q, Stauffer VL, Aurora SK, Láinez MJA.
Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies.
J Headache Pain. 2018 Dec 29;19(1):121. doi: 10.1186/s10194-018-0951-2. Epub 2018 Dec 29.
Abstract/Text BACKGROUND: Maintenance of effect following treatment with galcanezumab compared to placebo in adult patients with episodic or chronic migraine was evaluated.
METHODS: In 2 similarly designed studies of patients with episodic migraine (6 months) and 1 study of patients with chronic migraine (3 months), patients randomized in a 1:1:2 ratio received a subcutaneous injection of galcanezumab 120 mg/month (after an initial loading dose of 240 mg) or 240 mg/month or placebo. Maintenance of effect during the double-blind phase was evaluated based on a comparison of the percentages of galcanezumab- and placebo-treated patients with maintenance of 30, 50, 75, and 100% response (defined as ≥30, ≥50, ≥75, and 100% reduction from baseline in monthly migraine headache days [MHD]) at an individual patient level. Logistic regression analyses were used for between treatment comparisons.
RESULTS: A total of 1773 adult patients with episodic migraine (n = 444 for galcanezumab 120 mg; n = 435 for galcanezumab 240 mg; n = 894 for placebo for 2 studies pooled) and 1113 patients with chronic migraine (n = 278 for galcanezumab 120 mg; n = 277 for galcanezumab 240 mg; n = 558 for placebo) were evaluated. In patients with episodic migraine, ≥50% response was maintained in 41.5 and 41.1% of galcanezumab-treated patients (120 mg and 240 mg, respectively) for ≥3 consecutive months (until patient's endpoint) and 19.0 and 20.5%, respectively, for 6 consecutive months and was significantly greater than the 21.4 and 8.0% of placebo-treated patients at ≥3 and 6 months consecutively (P < 0.001). Approximately 6% of galcanezumab-treated patients maintained ≥75% response all 6 months versus 2% of placebo-treated patients. Few galcanezumab-treated patients maintained 100% response. In patients with chronic migraine, 29% of galcanezumab-treated patients maintained ≥30% response all 3 months compared to 16% of placebo patients while ≥50% response was maintained in 16.8 and 14.6% of galcanezumab-treated patients (120 mg and 240 mg) and was greater than placebo (6.3%; p < 0.001). Few patients maintained ≥75% response.
CONCLUSIONS: Treatment with galcanezumab 120 mg or 240 mg demonstrated statistically significant and clinically meaningful persistence of effect in patients with episodic migraine (≥3 and 6 consecutive months) and in patients with chronic migraine (for 3 months).
STUDY IDENTIFICATION AND TRIAL REGISTRATION: Study Identification: EVOLVE-1 (I5Q-MC-CGAG); EVOLVE-2 (I5Q-MC-CGAH); REGAIN (I5Q-MC-CGAI) TRIAL REGISTRATION: ClinicalTrials.gov ; NCT02614183 (EVOLVE-1); NCT02614196 (EVOLVE-2); NCT02614261 (REGAIN).

PMID 30594122
Sakai, Fumihiko. Ozeki, Akichika. Skljarevski V. Efficacy and safety of galcanezumab for prevention of migraine headache in Japanese patients with episodic migraine:a phase 2 randomized controlled clinical trial. Cephalalgia Reports. 2020;3.
Hirata K, Takeshima T, Sakai F, Tatsuoka Y, Suzuki N, Igarashi H, Nakamura T, Ozeki A, Yamazaki H, Skljarevski V.
A long-term open-label safety study of galcanezumab in Japanese patients with migraine.
Expert Opin Drug Saf. 2021 Jun;20(6):721-733. doi: 10.1080/14740338.2021.1866536. Epub 2021 Jan 4.
Abstract/Text BACKGROUND: Because of the burden of migraine in Japan, there is a need for safe and effective preventive treatments. This study assessed the long-term safety and tolerability of galcanezumab in Japanese patients with episodic (EM) or chronic (CM) migraine.
RESEARCH DESIGN AND METHODS: In this 12-month open-label study, adult patients with EM who previously completed a 6-month, double-blind, placebo-controlled trial were newly randomized to either galcanezumab dose from placebo or continued their assigned galcanezumab doses (all: 120 mg, n = 120; 240 mg, n = 126). Newly enrolled patients with CM were randomized to 120-mg (n = 32) or 240-mg (n = 33) galcanezumab. The primary outcome was long-term safety and tolerability.
RESULTS: The incidence of TEAEs was similar between treatment groups. Nasopharyngitis was the most common TEAE, followed by injection site reactions. The discontinuation rate was low (EM = 9.3%; CM = 15.4%) and no deaths were reported. Patients with EM who received galcanezumab in the placebo-controlled trial had sustained efficacy. Both doses reduced the number of migraine headache days in patients with CM.
CONCLUSIONS: Long-term treatment with 120-mg or 240-mg galcanezumab was safe and effective in Japanese patients with EM or CM.
TRIAL REGISTRATION: https://clinicaltrials.gov, identifier: NCT02959190.

PMID 33393835
Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E.
Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial.
JAMA. 2018 May 15;319(19):1999-2008. doi: 10.1001/jama.2018.4853.
Abstract/Text IMPORTANCE: Fremanezumab, a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, may be effective for treating episodic migraine.
OBJECTIVE: To assess the efficacy of fremanezumab compared with placebo for prevention of episodic migraine with a monthly dosing regimen or a single higher dose.
DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, parallel-group trial conducted at 123 sites in 9 countries from March 23, 2016 (first patient randomized), to April 10, 2017, consisting of a screening visit, 28-day pretreatment period, 12-week treatment period, and final evaluation at week 12.
PARTICIPANTS: Study participants were aged 18 to 70 years with episodic migraine (6-14 headache days, with at least 4 migraine days, during 28-day pretreatment period). Patients who had previous treatment failure with 2 classes of migraine-preventive medication were excluded.
INTERVENTIONS: Patients were randomized 1:1:1 to receive subcutaneous monthly dosing of fremanezumab (n = 290; 225 mg at baseline, week 4, and week 8); a single higher dose of fremanezumab, as intended to support a quarterly dose regimen (n = 291; 675 mg of fremanezumab at baseline; placebo at weeks 4 and 8); or placebo (n = 294; at baseline, week 4, and week 8).
MAIN OUTCOMES AND MEASURES: The primary end point was mean change in mean number of monthly migraine days during the 12-week period after the first dose.
RESULTS: Among 875 patients who were randomized (mean age, 41.8 [SD, 12.1] years; 742 women [85%]), 791 (90.4%) completed the trial. From baseline to 12 weeks, mean migraine days per month decreased from 8.9 days to 4.9 days in the fremanezumab monthly dosing group, from 9.2 days to 5.3 days in the fremanezumab single-higher-dose group, and from 9.1 days to 6.5 days in the placebo group. This resulted in a difference with monthly dosing vs placebo of -1.5 days (95% CI, -2.01 to -0.93 days; P < .001) and with single higher dosing vs placebo of -1.3 days (95% CI, -1.79 to -0.72 days; P < .001). The most common adverse events that led to discontinuation were injection site erythema (n = 3), injection site induration (n = 2), diarrhea (n = 2), anxiety (n = 2), and depression (n = 2).
CONCLUSIONS AND RELEVANCE: Among patients with episodic migraine in whom multiple medication classes had not previously failed, subcutaneous fremanezumab, compared with placebo, resulted in a statistically significant 1.3- to 1.5-day reduction in the mean number of monthly migraine days over a 12-week period. Further research is needed to assess effectiveness against other preventive medications and in patients in whom multiple preventive drug classes have failed and to determine long-term safety and efficacy.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02629861.

PMID 29800211
Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E.
Fremanezumab for the Preventive Treatment of Chronic Migraine.
N Engl J Med. 2017 Nov 30;377(22):2113-2122. doi: 10.1056/NEJMoa1709038.
Abstract/Text BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine.
METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose.
RESULTS: Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (±SE) reduction in the average number of headache days per month was 4.3±0.3 with fremanezumab quarterly, 4.6±0.3 with fremanezumab monthly, and 2.5±0.3 with placebo (P<0.001 for both comparisons with placebo). The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of hepatic function occurred in 5 patients in each fremanezumab group (1%) and 3 patients in the placebo group (<1%).
CONCLUSIONS: Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT02621931 .).

PMID 29171818
Silberstein SD, Cohen JM, Seminerio MJ, Yang R, Ashina S, Katsarava Z.
The impact of fremanezumab on medication overuse in patients with chronic migraine: subgroup analysis of the HALO CM study.
J Headache Pain. 2020 Sep 21;21(1):114. doi: 10.1186/s10194-020-01173-8. Epub 2020 Sep 21.
Abstract/Text BACKGROUND: We evaluated the efficacy of fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, in patients with chronic migraine (CM) with and without medication overuse (MO).
METHODS: In a 12-week, phase 3 trial, patients with CM were randomized to fremanezumab quarterly (675 mg/placebo/placebo), monthly (675 mg/225 mg/225 mg), or placebo. Post hoc analyses assessed the impact of fremanezumab in patients with and without MO (monthly use of acute headache medication ≥15 days, migraine-specific acute medication ≥10 days, or combination medication ≥10 days) on efficacy outcomes, including headache days of at least moderate severity (HDs), and six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life (MSQoL) questionnaire scores.
RESULTS: Of 1130 patients enrolled, 587 (51.9%) had baseline MO. Fremanezumab reduced placebo-adjusted least-squares mean (95% confidence interval) monthly HDs (- 2.2 [- 3.1 to - 1.2] and - 2.7 [- 3.7 to - 1.8]; P < 0.0001) in patients with MO and without MO (quarterly - 1.4 [- 2.3 to - 0.5], P = 0.0026; monthly - 1.4 [- 2.3 to - 0.6], P = 0.0017). Significantly more fremanezumab-treated patients had ≥ 50% reduction in HDs versus placebo, regardless of baseline MO (with: quarterly 70/201 [34.8%], monthly 78/198 [39.4%] vs placebo 26/188 [13.8%]; without: quarterly 71/174 [40.8%], monthly 75/177 [42.4%] vs placebo 41/183 [22.4%]). Fremanezumab improved HIT-6 and MSQoL scores. Significantly more fremanezumab-treated patients reverted to no MO (quarterly 111/201 [55.2%], monthly 120/198 [60.6%]) versus placebo (87/188 [46.3%]).
CONCLUSIONS: Fremanezumab is effective for prevention of migraine in patients with CM, regardless of MO, and demonstrated a benefit over placebo in reducing MO.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02621931 (HALO CM), registered December 12, 2012.

PMID 32958075
Sakai F, Suzuki N, Kim BK, Tatsuoka Y, Imai N, Ning X, Ishida M, Nagano K, Iba K, Kondo H, Koga N.
Efficacy and safety of fremanezumab for episodic migraine prevention: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in Japanese and Korean patients.
Headache. 2021 Jul;61(7):1102-1111. doi: 10.1111/head.14178. Epub 2021 Jul 29.
Abstract/Text OBJECTIVE: To evaluate the efficacy and safety of two dosing regimens of fremanezumab in Japanese and Korean patients with episodic migraine.
BACKGROUND: Episodic migraine, which accounts for more than 90% of migraine cases, is inadequately addressed by widely available preventive therapies. Fremanezumab, a monoclonal antibody that selectively targets the trigeminal sensory neuropeptide calcitonin gene-related peptide involved in migraine pathogenesis, has demonstrated efficacy in international Phase 3 trials of patients with both chronic and episodic migraine.
METHODS: This Phase 3 randomized, placebo-controlled trial randomly assigned patients with episodic migraine to receive subcutaneous fremanezumab monthly (225 mg at baseline, week 4, and week 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. The primary endpoint was the mean change from baseline in the monthly average number of migraine days during the 12-week treatment period after the first dose.
RESULTS: Of 357 patients enrolled (safety set, n = 356; full analysis set, n = 354), the least-squares mean (±standard error) reductions in the average number of migraine days per month during 12 weeks were significantly greater with fremanezumab monthly (-4.0 ± 0.4, n = 121) and fremanezumab quarterly (-4.0 ± 0.4, n = 117) than with placebo (-1.0 ± 0.4, n = 116; p < 0.0001 for both comparisons). The proportion of patients reaching at least a 50% reduction in the monthly average number of migraine days during the 12-week period after initial administration was also significantly improved with fremanezumab (fremanezumab monthly, 41.3%; fremanezumab quarterly, 45.3%; placebo, 11.2%; p < 0.0001 for both comparisons) as were other secondary endpoints (p < 0.001 for all comparisons between fremanezumab and placebo). Injection-site reactions were more common in fremanezumab-treated patients (fremanezumab monthly, 25.6%; fremanezumab quarterly, 29.7%; placebo, 21.4%).
CONCLUSION: Fremanezumab prevents episodic migraine in Japanese and Korean patients to a similar extent than in previously reported populations with no new safety concerns.

© 2021 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.
PMID 34323290
Sakai F, Suzuki N, Kim BK, Igarashi H, Hirata K, Takeshima T, Ning X, Shima T, Ishida M, Iba K, Kondo H, Koga N.
Efficacy and safety of fremanezumab for chronic migraine prevention: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in Japanese and Korean patients.
Headache. 2021 Jul;61(7):1092-1101. doi: 10.1111/head.14169. Epub 2021 Jul 29.
Abstract/Text OBJECTIVE: To determine the efficacy and safety of fremanezumab administration in Japanese and Korean patients with chronic migraine (CM).
BACKGROUND: Available preventive treatments for CM are limited by various efficacy and safety issues. Fremanezumab, a monoclonal antibody that targets the calcitonin gene-related peptide pathway involved in migraine pathogenesis, has been shown to be effective and well tolerated in large-scale, international Phase 3 trials.
METHODS: Randomized, placebo-controlled trial of patients with CM who received subcutaneous fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. Primary endpoint was the mean change from baseline in the monthly (28-day) average number of headache days of at least moderate severity during the 12 weeks after the first dose.
RESULTS: Among 571 patients randomized (safety set, n = 569; full analysis set, n = 566), the least-squares mean (±standard error [SE]) reduction in the average number of headache days of at least moderate severity per month during 12 weeks was significantly greater with fremanezumab monthly (-4.1 ± 0.4) and fremanezumab quarterly (-4.1 ± 0.4) than with placebo (-2.4 ± 0.4). The difference from the placebo group in the mean change (95% confidence interval [CI]) was -1.7 days (-2.54, -0.80) for the fremanezumab monthly group and -1.7 days (-2.55, -0.82) for the fremanezumab quarterly group (p < 0.001 vs. placebo for both fremanezumab groups). The percentage of patients with a ≥50% reduction in the average number of headache days of at least moderate severity per month (response rate) was higher with fremanezumab monthly (29.0%) and fremanezumab quarterly (29.1%) than with placebo (13.2%) in addition to other improvements in secondary endpoints, including reduction of acute medication use (mean change from baseline during 12-week period ± SE: fremanezumab monthly, -3.7 ± 0.4; fremanezumab quarterly, -3.9 ± 0.4; placebo, -2.4 ± 0.4) and improvements in disability scores (mean change from baseline in six-item Headache Impact Test score at 4 weeks after third injection ± SE: fremanezumab monthly, -8.1 ± 0.7; fremanezumab quarterly, -8.0 ± 0.7; placebo, -6.5 ± 0.7). Fremanezumab was well tolerated with a similar incidence of adverse events including injection-site reactions as placebo (patients with at least one treatment-emergent adverse event: fremanezumab total, n = 232 [61.4%]; placebo, n = 118 [61.8%]).
CONCLUSION: Fremanezumab effectively prevents CM in Japanese and Korean patients and was well tolerated. No safety signal was detected.

© 2021 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.
PMID 34324700
Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA.
A Controlled Trial of Erenumab for Episodic Migraine.
N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848.
Abstract/Text BACKGROUND: We tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine.
METHODS: We randomly assigned patients to receive a subcutaneous injection of either erenumab, at a dose of 70 mg or 140 mg, or placebo monthly for 6 months. The primary end point was the change from baseline to months 4 through 6 in the mean number of migraine days per month. Secondary end points were a 50% or greater reduction in mean migraine days per month, change in the number of days of use of acute migraine-specific medication, and change in scores on the physical-impairment and everyday-activities domains of the Migraine Physical Function Impact Diary (scale transformed to 0 to 100, with higher scores representing greater migraine burden on functioning).
RESULTS: A total of 955 patients underwent randomization: 317 were assigned to the 70-mg erenumab group, 319 to the 140-mg erenumab group, and 319 to the placebo group. The mean number of migraine days per month at baseline was 8.3 in the overall population; by months 4 through 6, the number of days was reduced by 3.2 in the 70-mg erenumab group and by 3.7 in the 140-mg erenumab group, as compared with 1.8 days in the placebo group (P<0.001 for each dose vs. placebo). A 50% or greater reduction in the mean number of migraine days per month was achieved for 43.3% of patients in the 70-mg erenumab group and 50.0% of patients in the 140-mg erenumab group, as compared with 26.6% in the placebo group (P<0.001 for each dose vs. placebo), and the number of days of use of acute migraine-specific medication was reduced by 1.1 days in the 70-mg erenumab group and by 1.6 days in the 140-mg erenumab group, as compared with 0.2 days in the placebo group (P<0.001 for each dose vs. placebo). Physical-impairment scores improved by 4.2 and 4.8 points in the 70-mg and 140-mg erenumab groups, respectively, as compared with 2.4 points in the placebo group (P<0.001 for each dose vs. placebo), and everyday-activities scores improved by 5.5 and 5.9 points in the 70-mg and 140-mg erenumab groups, respectively, as compared with 3.3 points in the placebo group (P<0.001 for each dose vs. placebo). The rates of adverse events were similar between erenumab and placebo.
CONCLUSIONS: Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months. The long-term safety and durability of the effect of erenumab require further study. (Funded by Amgen and Novartis; STRIVE ClinicalTrials.gov number, NCT02456740 .).

PMID 29171821
Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, Wright IK, Chou DE, Klatt J, Picard H, Lenz RA, Mikol DD.
One-year sustained efficacy of erenumab in episodic migraine: Results of the STRIVE study.
Neurology. 2020 Aug 4;95(5):e469-e479. doi: 10.1212/WNL.0000000000010019. Epub 2020 Jul 7.
Abstract/Text OBJECTIVE: To assess efficacy and tolerability of 1-year erenumab treatment in patients with episodic migraine.
METHODS: Patients were randomized (n = 955; 1:1:1) during the 24-week double-blind treatment phase (DBTP) to monthly subcutaneous placebo or erenumab 70 or 140 mg. At week 24, 845 patients were rerandomized (1:1) to erenumab 70 or 140 mg during the 28-week dose-blinded active-treatment phase (ATP). Monthly migraine days (MMD), achieving ≥50%, ≥75%, and 100% reduction in MMD, and safety/tolerability were assessed.
RESULTS: Mean MMD at DBTP baseline was 8.3. At week 52, mean changes (SE) from pre-DBTP baseline/week 24 (pre-ATP baseline) in MMD were -4.2 (0.2)/-1.1 (0.2) (70 mg) and -4.6 (0.2)/-1.8 (0.2) (140 mg) irrespective of treatment during the DBTP. For patients reducing dose from 140 (DBTP) to 70 mg (ATP), change in MMD from week 24 to 52 was -0.1 (0.3), and for those increasing from 70 (DBTP) to 140 mg (ATP), -1.8 (0.3). At week 52, 61.0%, 38.5%, and 19.8% of patients on erenumab 70 mg, and 64.9%, 40.8%, and 21.2% on erenumab 140 mg, achieved ≥50%, ≥75%, and 100% reduction in MMD from DBTP baseline, respectively. Among erenumab-treated patients in DBTP who showed ≥50% reduction in MMD during the last 3 months of DBTP and completed ATP, 86% showed sustained responses at ≥50% during the last 3 months of ATP. Safety of erenumab in ATP was similar to DBTP; exposure-adjusted incidence rates of adverse events were similar for either dose.
CONCLUSION: Over 52 weeks, erenumab provided sustained efficacy in episodic migraine; the safety profiles were similar between erenumab dose groups in the presence of dose blinding.
CLINICALTRIALSGOV IDENTIFIER: NCT02456740.
CLASSIFICATION OF EVIDENCE: Class II evidence that 52 weeks of treatment with erenumab 70 and 140 mg subcutaneously monthly results in sustained reductions in monthly migraine days and similar dose tolerability for patients with episodic migraine.

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PMID 32636324
Sakai F, Takeshima T, Tatsuoka Y, Hirata K, Lenz R, Wang Y, Cheng S, Hirama T, Mikol DD.
A Randomized Phase 2 Study of Erenumab for the Prevention of Episodic Migraine in Japanese Adults.
Headache. 2019 Nov;59(10):1731-1742. doi: 10.1111/head.13652. Epub 2019 Oct 14.
Abstract/Text OBJECTIVE: A phase 2, double-blind, placebo-controlled study to evaluate the efficacy and safety of erenumab for the prevention of episodic migraine in Japanese patients was conducted.
BACKGROUND: Previous global clinical studies have demonstrated the efficacy of erenumab in the prevention of migraine.
METHODS: Patients were randomized to placebo or erenumab 28, 70, or 140 mg administered subcutaneously once per month for 6 months. The primary endpoint was change from baseline in mean monthly migraine days over months 4-6 of the double-blind treatment phase. Secondary endpoints included the proportion of patients achieving ≥50% reduction from baseline in mean monthly migraine days (≥50% response) and change from baseline in mean monthly acute migraine-specific medication treatment days (MSMD) and mean Headache Impact Test (HIT-6™) scores. Efficacy outcomes were also determined at months 1, 2, and 3.
RESULTS: Four hundred and seventy five patients were randomized 2:1:2:2 to placebo and erenumab 28, 70, and 140 mg, respectively. Greater reductions in monthly migraine days were observed for erenumab vs placebo with differences of -1.25 (95% CI: -2.10 to -0.41; P = .004), -2.31 (95% CI: -3.00 to -1.62; P < .001), and -1.89 (95% CI: -2.58 to -1.20; P < .001) days for erenumab 28, 70, and 140 mg. The odds of having a ≥50% response were 3.2, 5.6, and 4.7 times greater for erenumab 28 mg (95% CI: 1.30-7.88; P = .009), 70 mg (95% CI: 2.60-12.06; P < .001), and 140 mg (95% CI: 2.24-9.99; P < .001) than for placebo. Greater reductions from baseline in mean acute monthly MSMD were observed for erenumab vs placebo with differences of -1.07 (95% CI: -1.80 to -0.35; P = .004), -2.07 (95% CI: -2.66 to -1.49; P < .001), and -2.04 (95% CI: -2.63 to -1.45; P < .001) days for erenumab 28, 70, and 140 mg. Erenumab 70 and 140 mg also resulted in greater improvements in HIT-6™ scores. The safety profile was similar across treatment groups. The most common adverse event was nasopharyngitis, which occurred in 29.4% of patients in the placebo group and 28.9%-33.3% of patients in the erenumab groups.
CONCLUSION: Monthly subcutaneous injections of erenumab 70 mg demonstrated statistically significant and numerically maximal efficacy with a favorable safety profile, suggesting that erenumab is a potential new therapy for migraine prevention in Japan.

© 2019 Amgen Inc. Headache: The Journal of Head and Face Pain published by Wiley Periodicals, Inc. on behalf of American Headache Society.
PMID 31612482
Takeshima T, Sakai F, Hirata K, Imai N, Matsumori Y, Yoshida R, Peng C, Cheng S, Mikol DD.
Erenumab treatment for migraine prevention in Japanese patients: Efficacy and safety results from a Phase 3, randomized, double-blind, placebo-controlled study.
Headache. 2021 Jun;61(6):927-935. doi: 10.1111/head.14138. Epub 2021 Jun 21.
Abstract/Text OBJECTIVES: Erenumab is a human anti-calcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. Global studies have demonstrated its efficacy in chronic and episodic migraine (EM). Here we report the outcomes from a Phase 3 study of erenumab in Japanese patients with chronic migraine (CM) or EM.
METHODS: Japanese patients with EM (<15 headache days/month, including ≥4 migraine days/month) or CM (≥15 headache days/month, including ≥8 migraine days/month) were randomized 1:1 to placebo or erenumab 70 mg once monthly for a 24-week double-blind treatment phase (DBTP). The primary endpoint of change from baseline in mean monthly migraine days (MMD) over months 4, 5, and 6 of the DBTP was compared between erenumab and placebo groups. Secondary efficacy and safety endpoints were also assessed.
RESULTS: A total of 261 patients were randomized to placebo (n = 131) or erenumab 70 mg (n = 130); all patients were included in the efficacy and safety analyses. The mean (standard deviation) MMD at baseline was 11.84 (5.70) for the placebo group and 12.40 (5.99) for erenumab 70 mg. The mean (standard error) change in MMD was -1.98 (0.38) for the placebo group (n = 131) and -3.60 (0.38) for erenumab 70 mg (n = 130). The difference in MMD reduction between groups was -1.67 (95% CI: -2.56, -0.78, p < 0.001) for EM and -1.57 (95% CI: -3.39, 0.24, p = 0.089) for CM. Adverse events (AEs) were consistent with earlier studies. The most frequent AEs (placebo, erenumab) were nasopharyngitis (28.2% and 26.9%, respectively), back pain (4.6% and 5.4%), and constipation (0.8% and 4.6%).
CONCLUSION: Treatment with erenumab 70 mg once monthly demonstrated favorable efficacy and safety findings in Japanese patients with EM or CM.

© 2021 Amgen Inc. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.
PMID 34153117
Headache Classification Committee of the International Headache Society (IHS).
The International Classification of Headache Disorders, 3rd edition (beta version).
Cephalalgia. 2013 Jul;33(9):629-808. doi: 10.1177/0333102413485658.
Abstract/Text
PMID 23771276
.
Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Headache Classification Committee of the International Headache Society.
Cephalalgia. 1988;8 Suppl 7:1-96.
Abstract/Text
PMID 3048700
Linn FH, Wijdicks EF, van der Graaf Y, Weerdesteyn-van Vliet FA, Bartelds AI, van Gijn J.
Prospective study of sentinel headache in aneurysmal subarachnoid haemorrhage.
Lancet. 1994 Aug 27;344(8922):590-3. doi: 10.1016/s0140-6736(94)91970-4.
Abstract/Text Retrospective surveys of patients with subarachnoid haemorrhage suggest that minor episodes with sudden headache (warning leaks) may precede rupture of an aneurysm, and that early recognition and surgery might lead to improved outcome. We studied 148 patients with sudden and severe headache (possible sentinel headache) seen by 252 general practitioners in a 5-year period in the Netherlands. Subarachnoid haemorrhage was the cause in 37 patients (25%) (proven aneurysm in 21, negative angiogram in 6, no angiogram done in 6, sudden headache followed by death in 4). 103 patients had headache as the only symptom, 12 of whom proved to have subarachnoid haemorrhage (6 with a ruptured aneurysm). Previous bouts of sudden headache had occurred in only 2. Other serious neurological conditions were diagnosed in 18. In the remaining 93, no underlying cause of headache was found; follow-up over 1 year showed no subsequent subarachnoid haemorrhage or sudden death. In this cohort, acute, severe headache in general practice indicated a serious neurological disorder in 37% (95% CI 29-45%), and subarachnoid haemorrhage in 25% (18-32%). 12% (5-18%) of those with headache as the only symptom. The notion of warning leaks as a less serious variant of subarachnoid haemorrhage is not supported by this study. Early recognition of subarachnoid haemorrhage is important but will probably have only limited impact on the outcome in the general population.

PMID 7914965
Landtblom AM, Fridriksson S, Boivie J, Hillman J, Johansson G, Johansson I.
Sudden onset headache: a prospective study of features, incidence and causes.
Cephalalgia. 2002 Jun;22(5):354-60. doi: 10.1046/j.1468-2982.2002.00368.x.
Abstract/Text Sudden onset headache is a common condition that sometimes indicates a life-threatening subarachnoid haemorrhage (SAH) but is mostly harmless. We have performed a prospective study of 137 consecutive patients with this kind of headache (thunderclap headache=TCH). The examination included a CT scan, CSF examination and follow-up of patients with no SAH during the period between 2 days and 12 months after the headache attack. The incidence was 43 per 100 000 inhabitants >18 years of age per year; 11.3% of the patients with TCH had SAH. Findings in other patients indicated cerebral infarction (five), intracerebral haematoma (three), aseptic meningitis (four), cerebral oedema (one) and sinus thrombosis (one). Thus no specific finding indicating the underlying cause of the TCH attack was found in the majority of the patients. A slightly increased prevalence of migraine was found in the non-SAH patients (28%). The attacks occurred in 11 cases (8%) during sexual activity and two of these had an SAH. Nausea, neck stiffness, occipital location and impaired consciousness were significantly more frequent with SAH but did not occur in all cases. Location in the temporal region and pressing headache quality were the only features that were more common in non-SAH patients. Recurrent attacks of TCH occurred in 24% of the non-SAH patients. No SAH occurred later in this group, nor in any of the other patients. It was concluded that attacks caused by a SAH cannot be distinguished from non-SAH attacks on clinical grounds. It is important that patients with their first TCH attack are investigated with CT and CSF examination to exclude SAH, meningitis or cerebral infarction. The results from this and previous studies indicate that it is not necessary to perform angiography in patients with a TCH attack, provided that no symptoms or signs indicate a possible brain lesion and a CT scan and CSF examination have not indicated SAH.

PMID 12110111
Edlow JA, Caplan LR.
Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage.
N Engl J Med. 2000 Jan 6;342(1):29-36. doi: 10.1056/NEJM200001063420106.
Abstract/Text
PMID 10620647
van Gijn J, van Dongen KJ.
The time course of aneurysmal haemorrhage on computed tomograms.
Neuroradiology. 1982;23(3):153-6. doi: 10.1007/BF00347559.
Abstract/Text We performed serial CT scans in a prospective series of 100 patients with a ruptured aneurysm who were first scanned within 2 days of the haemorrhage. In all patients the early CT scan showed evidence of extravasated blood. In 96 patients the source of bleeding was clearly at the base of the brain, and 32 of these had a haematoma. We estimated from the results of 139 repeat scans that the probability of recognizing an aneurysmal haemorrhage on CT is 85% after 5 days, 50% after 1 week, 30% after 2 weeks (mostly patients with haematomas), and almost nil after 3 weeks.

PMID 7088285
Uchihara T, Tsukagoshi H.
Jolt accentuation of headache: the most sensitive sign of CSF pleocytosis.
Headache. 1991 Mar;31(3):167-71. doi: 10.1111/j.1526-4610.1991.hed3103167.x.
Abstract/Text We prospectively examined the clinical signs of 54 febrile patients associated with recent-onset headache. They underwent lumbar puncture (LP) on suspicion of meningitis. The relation of each sign to cerebrospinal fluid (CSF) pleocytosis was estimated. Among 34 patients with pleocytosis, 33 had jolt accentuation (sensitivity: 97.1%), while only 5 of them had neck stiffness or Kernig's sign. Among 20 patients without pleocytosis, 12 had no jolt accentuation (specificity: 60%). We found jolt accentuation to be the most sensitive sign of CSF pleocytosis. If jolt accentuation is noted in a febrile patient associated with recent onset headache, the CSF should be examined even in the absence of neck stiffness or Kernig's sign.

PMID 2071396
Nakao JH, Jafri FN, Shah K, Newman DH.
Jolt accentuation of headache and other clinical signs: poor predictors of meningitis in adults.
Am J Emerg Med. 2014 Jan;32(1):24-8. doi: 10.1016/j.ajem.2013.09.012. Epub 2013 Oct 16.
Abstract/Text Jolt accentuation or exacerbation of a baseline headache with horizontal rotation of the neck is a physical finding believed to assess for meningeal irritation. We conducted a prospective observational study of neurologically intact emergency department (ED) patients undergoing lumbar puncture in 2 inner city academic EDs to validate the sensitivity and specificity of jolt accentuation and to assess the sensitivity and specificity of Kernig sign, Brudzinski sign, and nuchal rigidity, in predicting cerebrospinal fluid (CSF) pleocytosis in individuals being assessed for meningitis. Adult patients 18 years and older undergoing lumbar puncture between 2006 and 2009 were approached for consent. Exclusions included inability to consent and altered mental status. Physicians were asked to answer a questionnaire of physical examination findings before receiving CSF results. The primary outcome was the presence or absence of pleocytosis, defined as greater than or equal to 5 cells/high-power field in the fourth CSF tube. We calculated descriptive statistics and tests of diagnostic accuracy. A total of 230 patients consented for participation and had CSF white blood cell counts recorded. Forty-seven individuals (20%) had pleocytosis. A total of 197 patients had headache and were, hence, eligible for jolt accentuation assessment. For pleocytosis, the sensitivity of jolt accentuation was 21%, Kernig sign was 2%, Brudzinski sign was 2%, and nuchal rigidity was 13%. The specificity of jolt accentuation was 82%, Kernig sign was 97%, Brudzinski sign was 98%, and nuchal rigidity was 80%. Jolt accentuation in our cohort was poorly predictive of pleocytosis and insensitive. The presence of Kernig sign, Brudzinski sign, or nuchal rigidity has moderate positive but no negative predictive value for pleocytosis.

© 2013.
PMID 24139448
Tamune H, Takeya H, Suzuki W, Tagashira Y, Kuki T, Nakamura M.
Absence of jolt accentuation of headache cannot accurately rule out meningitis in adults.
Am J Emerg Med. 2013 Nov;31(11):1601-4. doi: 10.1016/j.ajem.2013.08.028. Epub 2013 Sep 23.
Abstract/Text BACKGROUND: Meningitis is a common emergency disease. Signs and symptoms easily observed at the bedside are needed because early recognition of the possibility of meningitis is necessary for the decision to perform lumbar puncture. Jolt accentuation of headache has been reported to be the most sensitive diagnostic test; however, limited articles have reproduced its sensitivity.
METHODS: This is a single-center retrospective medical record review between 2007 and 2012. We diagnosed meningitis based on the criterion standard that cerebrospinal fluid total cells is more than 5/mm(3), in accordance with previous studies. All diagnostic and management decisions including Kernig sign, nuchal rigidity, and jolt accentuation of headache were at the physician's discretion. We calculated the sensitivity and specificity of well-known signs and symptoms of meningitis and, especially, compared the efficacy of jolt accentuation of headache with previous studies.
RESULTS: We investigated 531 adult patients who were suspected of meningitis and had lumbar puncture performed. Of these patients, 139 had meningitis. Background characteristics and vital signs were not clinically different between the 2 groups, although classic tetralogy of bacterial meningitis (fever, nuchal rigidity, mental disturbance, and headache) was worth investigated. The sensitivity and specificity of jolt accentuation of headache were 63.9% (95% confidence interval, 51.9%-76.0%) and 43.2% (34.7%-51.6%), respectively.
CONCLUSION: The absence of jolt accentuation of headache test cannot, on its own, accurately rule out meningitis in adults. Further studies are warranted to reproduce this result and to discover better bedside diagnostic tests.

© 2013.
PMID 24070978
Gonzalez-Gay MA, Lopez-Diaz MJ, Barros S, Garcia-Porrua C, Sanchez-Andrade A, Paz-Carreira J, Martin J, Llorca J.
Giant cell arteritis: laboratory tests at the time of diagnosis in a series of 240 patients.
Medicine (Baltimore). 2005 Sep;84(5):277-290. doi: 10.1097/01.md.0000180043.19285.54.
Abstract/Text The outcome of a patient with giant cell arteritis (GCA) is closely related to the development of severe ischemic manifestations. In the current study we analyzed the implications of routine laboratory tests obtained at the time of diagnosis in the clinical spectrum of a series of 240 consecutive patients with biopsy-proven GCA at the single hospital for a defined population. We also examined whether the laboratory markers of inflammation may be predictors of severe ischemic manifestations (visual ischemic events, cerebrovascular accidents, jaw claudication, or large-artery stenosis of the extremities of recent onset), and their potential correlation. Anemia (hemoglobin <12 g/dL) was observed in 131 (54.6%) and thrombocytosis in 117 (48.8%) patients. Sixty-eight (28.3%) patients had leukocytosis. The percentage of patients showing a significant increase of alkaline phosphatase and hypoalbuminemia was similar (25% and 27.8%, respectively). The mean values of erythrocyte sedimentation rate (ESR) and C-reactive protein were 93 +/- 23 mm/h and 94 +/- 63 mg/L, respectively. A strong correlation among most laboratory markers of inflammation was observed. Anemia was more commonly observed in patients without severe ischemic manifestations (61.5% versus 48.9% in those with severe ischemic manifestation; p = 0.05) and in patients with constitutional syndrome or fever (p < 0.001). Patients with ESR greater than 100 mm/h exhibited more commonly constitutional syndrome (p < 0.001) and had a statistically significant reduction in the incidence of visual ischemic events (p < 0.025). Only 7 (22.6%) of the 31 patients who suffered permanent visual loss had an ESR at the time of disease diagnosis greater than 100 mm/h. However, in a multivariate logistic regression analysis, only anemia was found to be a negative predictor for the development of severe ischemic manifestations of GCA (odds ratio, 0.53; 95% confidence intervals, 0.30-0.94; p = 0.03). In conclusion, our results suggest that some laboratory markers of inflammation, in particular the presence of anemia, may negatively predict the risk of severe ischemic complications in GCA patients.

PMID 16148728
Hall S, Persellin S, Lie JT, O'Brien PC, Kurland LT, Hunder GG.
The therapeutic impact of temporal artery biopsy.
Lancet. 1983 Nov 26;2(8361):1217-20. doi: 10.1016/s0140-6736(83)91269-2.
Abstract/Text To evaluate the clinical usefulness of temporal artery biopsy in the diagnosis of giant-cell arteritis we followed up all 134 residents of Olmsted County, Minnesota, who had temporal artery biopsies between 1965 and 1980. Initial biopsies were positive for giant-cell arteritis in 46 cases and negative in 88. A history of jaw pain or claudication and the findings of a palpably abnormal temporal artery were significantly more common in the patients whose biopsy specimens showed giant-cell arteritis. Over a median follow-up period of 70 months (range 1-192) only 8 of the 88 biopsy-negative patients had clinical courses requiring long-term, high-dose corticosteroid therapy for giant-cell arteritis. In this population-based study temporal artery biopsy correctly predicted the subsequent need for corticosteroid therapy in 94% of cases: these findings indicate that biopsy should be done before patients are committed to long-term corticosteroid therapy.

PMID 6139569
Cifelli A, Vaithianathar L.
Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL).
BMJ Case Rep. 2011 Mar 29;2011. doi: 10.1136/bcr.03.2010.2862. Epub 2011 Mar 29.
Abstract/Text A lady in her late 20s was admitted with a history of headaches and intermittent focal neurological symptoms which were greatly exacerbated by catheter angiography of the cerebral circulation. Cerebrospinal fluid analysis demonstrated a lymphocytic pleocytosis. She subsequently made a spontaneous recovery, without neurological sequelae. Her presentation fits the diagnostic criteria for the previously described syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL). HaNDL is a probably underdiagnosed nosological entity, characterised by often dramatic clinical manifestations but ultimately a good prognosis.

PMID 22700346
Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB.
Narrative review: reversible cerebral vasoconstriction syndromes.
Ann Intern Med. 2007 Jan 2;146(1):34-44. doi: 10.7326/0003-4819-146-1-200701020-00007.
Abstract/Text Reversible cerebral vasoconstriction syndromes (RCVS) comprise a group of diverse conditions, all characterized by reversible multifocal narrowing of the cerebral arteries heralded by sudden (thunderclap), severe headaches with or without associated neurologic deficits. Reversible cerebral vasoconstriction syndromes are clinically important because they affect young persons and can be complicated by ischemic or hemorrhagic strokes. The differential diagnosis of RCVS includes conditions associated with thunderclap headache and conditions that cause irreversible or progressive cerebral artery narrowing, such as intracranial atherosclerosis and cerebral vasculitis. Misdiagnosis as primary cerebral vasculitis and aneurysmal subarachnoid hemorrhage is common because of overlapping clinical and angiographic features. However, unlike these more ominous conditions, RCVS is usually self-limited: Resolution of headaches and vasoconstriction occurs over a period of days to weeks. In this review, we describe our current understanding of RCVS; summarize its key clinical, laboratory, and imaging features; and discuss strategies for diagnostic evaluation and treatment.

PMID 17200220
Ducros A, Fiedler U, Porcher R, Boukobza M, Stapf C, Bousser MG.
Hemorrhagic manifestations of reversible cerebral vasoconstriction syndrome: frequency, features, and risk factors.
Stroke. 2010 Nov;41(11):2505-11. doi: 10.1161/STROKEAHA.109.572313. Epub 2010 Sep 30.
Abstract/Text BACKGROUND AND PURPOSE: Reversible cerebral vasoconstriction syndrome (RCVS), characterized by severe headaches and reversible constriction of cerebral arteries, may be associated with ischemic and hemorrhagic strokes. The aim of this study was to describe the frequency, patterns, and risk factors of intracranial hemorrhages in RCVS.
METHODS: We analyzed prospective data on 89 consecutive patients with RCVS, of which 8 were postpartum and 46 used vasoactive substances. Standard bivariate and multivariate statistical tests were applied to compare patients with and without hemorrhage.
RESULTS: Thirty patients (34%), of which 5 were postpartum and 12 used vasoactive substances, developed at least 1 type of intracranial hemorrhage, including cortical subarachnoid (n = 27), intracerebral (n = 11), and subdural hemorrhage (n=2). Patients with hemorrhage had an older age (46.6 versus 41.6 years, P = 0.049) and were more frequently females (90% versus 51%, P = 0.0017) or were migrainers (43% versus 19%, P = 0.022) than those without hemorrhage. Multivariate testing identified 2 independent risk factors of hemorrhage in RCVS: female gender (OR, 4.05; 95% CI, 1.46 to 11.2) and migraine (OR, 2.34; 95% CI, 1.06 to 5.18). Patients with hemorrhage had a greater risk of persistent focal deficits (30% versus 2%, P = 0.0002), cerebral infarction (13% versus 2%, P = 0.039), posterior reversible encephalopathy syndrome (17% versus 3%, P = 0.041) at the acute stage, and of inability to resume normal activities at 6 months (27% versus 0%, P < 0.0001).
CONCLUSIONS: In RCVS, women and migrainers seem to be at higher risk of intracranial hemorrhage. Overall, intracranial hemorrhages are frequent in RCVS and are associated with a more severe clinical spectrum.

PMID 20884871
Ducros A, Hajj-Ali RA, Singhal AB, Wang SJ.
Reversible cerebral vasoconstriction syndrome.
JAMA Neurol. 2014 Mar;71(3):368. doi: 10.1001/jamaneurol.2013.5875.
Abstract/Text
PMID 24614989
Detsky ME, McDonald DR, Baerlocher MO, Tomlinson GA, McCrory DC, Booth CM.
Does this patient with headache have a migraine or need neuroimaging?
JAMA. 2006 Sep 13;296(10):1274-83. doi: 10.1001/jama.296.10.1274.
Abstract/Text CONTEXT: In assessing the patient with headache, clinicians are often faced with 2 important questions: Is this headache a migraine? Does this patient require neuroimaging? The diagnosis of migraine can direct therapy, and information obtained from the history and physical examination is used by physicians to determine which patients require neuroimaging.
OBJECTIVE: To determine the usefulness of the history and physical examination that distinguish patients with migraine from those with other headache types and that identify those patients who should undergo neuroimaging.
DATA SOURCES AND STUDY SELECTION: A systematic review was performed using articles from MEDLINE (1966-November 2005) that assessed the performance characteristics of screening questions in diagnosing migraine (with the International Headache Society diagnostic criteria as a gold standard) and addressed the accuracy of the clinical examination in predicting the presence of underlying intracranial pathology (with computed tomography/magnetic resonance imaging as the reference standard).
DATA EXTRACTION: Two authors independently reviewed each study to determine eligibility, abstract data, and classify methodological quality using predetermined criteria. Disagreement was resolved by consensus with a third author.
DATA SYNTHESIS: Four studies of screening questions for migraine (n = 1745 patients) and 11 neuroimaging studies (n = 3725 patients) met inclusion criteria. All 4 of the migraine studies illustrated high sensitivity and specificity if 3 or 4 criteria were met. The best predictors can be summarized by the mnemonic POUNDing (Pulsating, duration of 4-72 hOurs, Unilateral, Nausea, Disabling). If 4 of the 5 criteria are met, the likelihood ratio (LR) for definite or possible migraine is 24 (95% confidence interval [CI], 1.5-388); if 3 are met, the LR is 3.5 (95% CI, 1.3-9.2), and if 2 or fewer are met, the LR is 0.41 (95% CI, 0.32-0.52). For the neuroimaging question, several clinical features were found on pooled analysis to predict the presence of a serious intracranial abnormality: cluster-type headache (LR, 10.7; 95% CI, 2.2-52); abnormal findings on neurologic examination (LR, 5.3; 95% CI, 2.4-12); undefined headache (ie, not cluster-, migraine-, or tension-type) (LR, 3.8; 95% CI, 2.0-7.1); headache with aura (LR, 3.2; 95% CI, 1.6-6.6); headache aggravated by exertion or a valsalva-like maneuver (LR, 2.3; 95% CI, 1.4-3.8); and headache with vomiting (LR, 1.8; 95% CI, 1.2-2.6). No clinical features were useful in ruling out significant pathologic conditions.
CONCLUSIONS: The presence of 4 simple historical features can accurately diagnose migraine. Several individual clinical features were found to be associated with a significant intracranial abnormality, and patients with these features should undergo neuroimaging.

PMID 16968852
Lipton RB, Dodick D, Sadovsky R, Kolodner K, Endicott J, Hettiarachchi J, Harrison W; ID Migraine validation study.
A self-administered screener for migraine in primary care: The ID Migraine validation study.
Neurology. 2003 Aug 12;61(3):375-82. doi: 10.1212/01.wnl.0000078940.53438.83.
Abstract/Text BACKGROUND: Migraine is a highly prevalent and disabling illness that remains substantially undiagnosed in primary care. Because of the potential value of a screening tool, the current study was designed to establish the validity and reliability of a brief, self-administered migraine screener in patients with headache complaints in the primary care setting.
METHODS: A total of 563 patients presenting for routine primary care appointments and reporting headaches in the past 3 months completed a self-administered migraine screener. All patients were then referred for an independent diagnostic evaluation by a headache expert, of whom 451 (80%) completed a full evaluation. Migraine diagnosis was assigned based on International Headache Society criteria after completing a semi-structured diagnostic interview.
RESULTS: Of nine diagnostic screening questions, a three-item subset of disability, nausea, and sensitivity to light provided optimum performance, with a sensitivity of 0.81 (95% CI, 0.77 to 0.85), a specificity of 0.75 (95% CI, 0.64 to 0.84), and positive predictive value of 0.93 (95% CI, 89.9 to 95.8). Test-retest reliability was good, with a kappa of 0.68 (95% CI, 0.54 to 0.82). The sensitivity and specificity of the three-item migraine screener was similar regardless of sex, age, presence of other comorbid headaches, or previous diagnostic status.
CONCLUSIONS: The three-item ID Migraine migraine screener was found to be a valid and reliable screening instrument for migraine headaches. Its ease of use and operating characteristics suggest that it could significantly improve migraine recognition in primary care.

PMID 12913201
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
竹島多賀夫 : 報酬額((株)ヘッジホッグ・メドテック,沢井製薬(株),帝人ファーマ(株)),講演料(大塚製薬(株),アムジェン(株),日本イーライリリー(株),第一三共(株)),研究費・助成金など(日本イーライリリー(株),ファイザー(株),ルンドベック・ジャパン,アッヴィ合同会社)[2024年]
監修:高橋裕秀 : 特に申告事項無し[2025年]

ページ上部に戻る

頭痛

戻る