MIGRAINEMIGRAINE

臺北榮民總醫院 神經醫學中心臺北榮民總醫院 神經醫學中心

陳韋達陳韋達

OutlineOutline

Clinical diagnosis and evaluation of Clinical diagnosis and evaluation of migrainemigraine

Pathophysiology of migrainePathophysiology of migraine

Treatment of migraineTreatment of migraine

Origin of HeadacheOrigin of Headache

Distention, traction, or dilatation of intracranail or extracraDistention, traction, or dilatation of intracranail or extracranial nial arteriesarteries

Traction or displacement of large intracranialTraction or displacement of large intracranial veins veins or thei or their r duraldural envelope envelope

Compression, traction, or inflammation of cranial and spiCompression, traction, or inflammation of cranial and spinal nal nervesnerves

Spasm, inflammation, and trauma to cranial and cervical Spasm, inflammation, and trauma to cranial and cervical musclesmuscles

MeningealMeningeal irritation and raised intracranial pressure irritation and raised intracranial pressure

Perturbation of intracerebral Perturbation of intracerebral serotonergicserotonergic projections projections i impaired central inhibition?mpaired central inhibition?

Diagnosis of Headache DisordersDiagnosis of Headache Disorders

International Classification of Headache Disorders (ICHD)International Classification of Headache Disorders (ICHD)– Conducted by the Headache Classification SubcommittConducted by the Headache Classification Subcommitt

ee of International Headache Society (IHS)ee of International Headache Society (IHS)– ICHD-1, 1988 ICHD-1, 1988 (( 中譯版：臺大 洪祖培等中譯版：臺大 洪祖培等 ))– ICHD-2, 2004ICHD-2, 2004 ( ( 中譯版：臺灣神經學會頭痛學組中譯版：臺灣神經學會頭痛學組 ))

11 、偏頭痛、偏頭痛 22 、緊縮型頭痛、緊縮型頭痛 33 、叢發性頭痛與其他三叉自律神經頭痛、叢發性頭痛與其他三叉自律神經頭痛 44 、其他原發性頭痛、其他原發性頭痛 55 、歸因於頭部及頸部外傷之頭痛、歸因於頭部及頸部外傷之頭痛 66 、歸因於顱部或頸部血管疾患之頭痛、歸因於顱部或頸部血管疾患之頭痛 77 、歸因於非血管性顱內疾患之頭痛、歸因於非血管性顱內疾患之頭痛 88 、歸因於與物質或物質戒斷之頭痛、歸因於與物質或物質戒斷之頭痛 99 、歸因於感染之頭痛、歸因於感染之頭痛 1010 、歸因於與体內恒定疾患之頭痛、歸因於與体內恒定疾患之頭痛 1111 、歸因於頭顱、頸、眼、耳、鼻、鼻竇、牙、口或其他面部或顱部結構疾 、歸因於頭顱、頸、眼、耳、鼻、鼻竇、牙、口或其他面部或顱部結構疾 患之頭痛或顏面痛患之頭痛或顏面痛 1212 、歸因於精神疾患之頭痛、歸因於精神疾患之頭痛 1313 、顱神經痛和中樞性顏面痛、顱神經痛和中樞性顏面痛 1414 、其他頭痛、顱部神經痛、中樞或原發性顏面痛、其他頭痛、顱部神經痛、中樞或原發性顏面痛

國際頭痛疾病分類 國際頭痛疾病分類 ICHD-2 ICHD-2 2003/92003/9

有多少人頭痛有多少人頭痛 96% 96% 以上的人畢生會發生一次以上頭痛以上的人畢生會發生一次以上頭痛 1997-1999 1997-1999 大臺北地區頭痛調查 大臺北地區頭痛調查 (15(15 歲以上歲以上 ))

女性：女性： 14% 14% 偏頭痛，偏頭痛， 57% 57% 其他頭痛，其他頭痛， 29% 29% 無無男性：男性： 5% 5% 偏頭痛，偏頭痛， 46% 46% 其他頭痛，其他頭痛， 50% 50% 無無

全臺灣全臺灣 1515 歲以上成人約 歲以上成人約 9.7 % (1509.7 % (150 萬萬 ) ) 的人有偏頭痛 的人有偏頭痛 (( 女女 115115 萬，男萬，男 3535 萬，約萬，約 33 ：： 1)1)

約約 4% (604% (60 萬萬 ) ) 的人其頭痛平均天數每個月超過的人其頭痛平均天數每個月超過 1515 天，符天，符合慢性每日頭痛的診斷。其中三成濫用止痛藥。 合慢性每日頭痛的診斷。其中三成濫用止痛藥。

Adjusted Age-specific Prevalence of MigraineAdjusted Age-specific Prevalence of Migraine

Women

Men

偏頭痛發作偏頭痛發作 前趨症狀 前趨症狀 (premonitory symptoms)(premonitory symptoms)

疲倦、注意力差、頸部僵硬、想吃東西、呵欠疲倦、注意力差、頸部僵硬、想吃東西、呵欠 預兆 預兆 (aura)(aura)

視覺預兆視覺預兆 : : 閃光、星星、盲點、愛麗絲仙境閃光、星星、盲點、愛麗絲仙境感覺異常感覺異常 : : 手指末端有針刺感手指末端有針刺感運動障礙：半側偏癱運動障礙：半側偏癱語言障礙：失語症口齒不清語言障礙：失語症口齒不清

頭痛發作 頭痛發作 (headache)(headache)

發作結束 發作結束 (postdrome)(postdrome)

無預兆偏頭痛 無預兆偏頭痛 (migraine without aura)(migraine without aura)

A. A. 至少有五次以上頭痛發作符合 至少有五次以上頭痛發作符合 B, C B, C 和 和 D D 項項 B. B. 頭痛過程持續 頭痛過程持續 4-724-72 小時小時 [[ 沒治療或治療沒成功沒治療或治療沒成功 ] ] C. C. 至少有以下四項中的兩項至少有以下四項中的兩項

一側的頭痛 一側的頭痛 搏動性的頭痛 搏動性的頭痛 頭痛中度到嚴重頭痛中度到嚴重 [[ 會影響工作生活會影響工作生活 ] ] 日常活動如走路或爬樓梯等會使頭痛加劇 日常活動如走路或爬樓梯等會使頭痛加劇

D. D. 至少有以下兩項中的一項至少有以下兩項中的一項噁心或嘔吐 噁心或嘔吐 畏光及怕吵 畏光及怕吵

E. E. 非歸因於其他疾患非歸因於其他疾患

診斷標準診斷標準

預兆偏頭痛 預兆偏頭痛 (Migraine with aura)(Migraine with aura)

A. A. 至少有兩次以上頭痛發作符合 至少有兩次以上頭痛發作符合 B B 項項 B. B. 預兆至少包括下列一項預兆至少包括下列一項

– 完全可逆視覺症狀完全可逆視覺症狀– 完全可逆感覺症狀完全可逆感覺症狀– 完全可逆失語性語言障礙完全可逆失語性語言障礙

C. C. 至少具下列兩項至少具下列兩項– 同名側的視覺症狀及同名側的視覺症狀及 // 或單側感覺症狀或單側感覺症狀– 至少一種預兆在至少一種預兆在≥≥ 55分鐘逐漸產生，及分鐘逐漸產生，及 // 或不同預兆在 ≥或不同預兆在 ≥

55分鐘相繼發生分鐘相繼發生– 每一種狀持續 ≥每一種狀持續 ≥ 55分鐘及 ≤分鐘及 ≤ 6060分鐘分鐘

D. D. 符合無預兆偏頭痛基準 符合無預兆偏頭痛基準 B-D B-D 的頭痛，在預兆同時或預 的頭痛，在預兆同時或預 兆之後的兆之後的 6060分鐘內發生分鐘內發生

E. E. 非歸因於其他疾患 非歸因於其他疾患

診斷標準診斷標準

頭痛日誌頭痛日誌

記錄重點

1、疼痛程度

2、疼痛時段

3 、相關症狀及預兆

4、持續時間

5 、服用葯物及其有效程度

6、月經日期

偏頭痛的診斷工具偏頭痛的診斷工具

頭痛疾患的診斷工具頭痛疾患的診斷工具

頭痛日誌頭痛日誌– 頭痛位置、性質、伴隨症狀、時間與頻率因素、預兆、頭痛位置、性質、伴隨症狀、時間與頻率因素、預兆、誘發原因、月經日期誘發原因、月經日期

神經放射線檢查神經放射線檢查– Frishberg BM 1994: CT or MRI for migraineurs with noFrishberg BM 1994: CT or MRI for migraineurs with no

rmal NE shows positive findings in 4/987(0.4%) : 3 witrmal NE shows positive findings in 4/987(0.4%) : 3 with tumor, 1 with AVMh tumor, 1 with AVM

實驗室檢查實驗室檢查– 腦血管攝影、腰椎穿刺、腦波、腦血管超音波、眼底及腦血管攝影、腰椎穿刺、腦波、腦血管超音波、眼底及眼壓檢查、耳鼻喉科檢查眼壓檢查、耳鼻喉科檢查

Headache?

Migraine or other primary headaches

hyper-acute onset

Posture-related

One-sided pain+ cranial autonomic s/s

Associated w/ recent event

medication overuse

thunderclap headache

intracranial HTN

Trigeminal-autonomic cephalalgia

Secondary headache

Medication-overuse headache

Diagnostic flow chart of headache

偏頭痛的後遺症偏頭痛的後遺症

慢性偏頭痛 慢性偏頭痛 (chronic migraine)(chronic migraine)

偏頭痛重積狀態 偏頭痛重積狀態 (status Migrainosus)(status Migrainosus)

– 定義：偏頭痛發作時間超過三天，無頭痛時間定義：偏頭痛發作時間超過三天，無頭痛時間少於少於 44 小時 小時 (( 不含睡眠不含睡眠 ))

無梗塞之持續性預兆 無梗塞之持續性預兆 (persistent aura without infarction)(persistent aura without infarction)

偏頭痛梗塞 偏頭痛梗塞 (migrainous Infarction(migrainous Infarction))– 預兆持續一小時以上併影像學之腦梗塞証據預兆持續一小時以上併影像學之腦梗塞証據

偏頭痛引發之癲癇發作 偏頭痛引發之癲癇發作 (migraine-triggered seizure)(migraine-triggered seizure)

Deep White Matter Lesions

Kruit MC, et al. JAMA 2004; 291: 427-34Kruit MC, et al. JAMA 2004; 291: 427-34

偏頭痛的後遺症偏頭痛的後遺症

Risk Factors for Chronic Daily Headache Risk Factors for Chronic Daily Headache (CDH)(CDH)

A history of migraineA history of migraine

Medication overuseMedication overuse

Caffeine consumptionCaffeine consumption- Dietary and medications- Dietary and medications

ObesityObesity （（ OR=5.3OR=5.3 ））SnoringSnoring （（ OR=3.3OR=3.3 ））Stressful Life EventsStressful Life Events

Wang SJ. et al. Neurology 2000;54:31 4-9Scher AJ et al. Neurology 2002 ； 58(S3):A332Scher AJ et al. Neurology Pain 2003;106:81-9Lu SR et al.Cephalalgia 2001;21:980-6Juang KD,et al. Cephalalgia 2004;24:54-9Katsarava Z et al. Neurology 2004;62:788-90

Migraine Comorbid and Co-occurring Disorders

Cardiovascular

HypertensionMitral valve prolapsePatent foramen ovaleRaynaud’s phenomenonStroke

Psychiatric

DepressionAnxietyBipolar disorderEating disorders． Anorexia / bulimia． Obesity

　 Neurologic

Seizure disorder

Gastrointestinal

Gastric ulcersIrritable bowel syndrome

Pulmonary

SmokingAsthmaAllergies

Chronic pain

FibromyalgiaChronic fatigue syndrome

　Endocrine

Menstrual abnormalitiesHypothyroidism

Migraine with aura is associated with Migraine with aura is associated with cerebrovascular diseasecerebrovascular disease

Myocardial infarction (MI) (OR 2.08)Myocardial infarction (MI) (OR 2.08)

Coronary revascularisation (1.74)Coronary revascularisation (1.74)

Angina (1.71)Angina (1.71)

Death from ischemic cardiovascular disease (2.33)Death from ischemic cardiovascular disease (2.33)

Patent foramen ovale (PFO)Patent foramen ovale (PFO)

Other associated CV risks Other associated CV risks – Unfavourable cholesterol profileUnfavourable cholesterol profile– High blood pressureHigh blood pressure– Parental history of early MIParental history of early MI

Kurth T, 2008; kurth T, 2007; Scher AI 2005

OutlineOutline

Clinical diagnosis and evaluation of Clinical diagnosis and evaluation of migrainemigraine

Pathophysiology of migrainePathophysiology of migraine

Treatment of migraineTreatment of migraine

“The concept of migraine is a state of central neuronal hyperexcitability.”

Welch KMA 1990

Hypersensitivity to external stimuliHypersensitivity to external stimuliin Migrainein Migraine

Sensitivity to light, sound, and odorsSensitivity to light, sound, and odors– InterictalInterictal– ictal ictal

Attacks triggered by light or other sensory stimuliAttacks triggered by light or other sensory stimuli

Visual discomfort and intenseVisual discomfort and intense

illusion to grating patternsillusion to grating patterns

Deficient habituation in migraineDeficient habituation in migraine

Schoenen J et al, Eur J Neurol 1995;2:115-122

Check size=8 min, reversal rate =3.1 hz

Deficient habituation in migraineDeficient habituation in migraine

Afra J et al., Brain 1998; 121:233-241Check size=8 min, reversal rate =3.1 hz

Serotonin may be involved in Serotonin may be involved in presynaptic depressionpresynaptic depression

Principles of Neural Science, 4/e

Thalamus

Repeated Stimuli

Ach

His

DANE

5-HT

Basalforebrain

Brainstem

State-settingchemically addressedconnections

Cephalalgia 2007; 27:1429-1439

Ach

His

DANE

5-HTBasal

forebrainBrainstem

State-settingchemically addressedconnections

Thalamocortical loops

Sensory cortex

Habituation Depends on Habituation Depends on Subcortical-cortical Aminergic ProjectionsSubcortical-cortical Aminergic Projections

Migraine: a neurochemical disorder with Migraine: a neurochemical disorder with low serotonergic disposition low serotonergic disposition

InterictalInterictal– Plasma 5HT↓; HIAA↑Plasma 5HT↓; HIAA↑

IctalIctal– Urine 5-HIAA↑ Urine 5-HIAA↑ – Plasma 5HT↑; HIAA↓Plasma 5HT↑; HIAA↓

Int Arch Allergy Appl Immunol 1961;19:55-8Cephalalgia 2007;27:1296-1300

Ictal Serotonin Change in MigraineIctal Serotonin Change in Migraine

Acute headache Sumatriptan Interictal Neurology 2008;70:431-9

Fluoxetine reverses VEP dishabituation Fluoxetine reverses VEP dishabituation in migrainein migraine

Headache 2002;42:582-7

Headache 2002;42:582-7

-9.3% -10.1%

Fluoxetine 20mg/dx 1 mo

Homeostatic Changes and Homeostatic Changes and Altered Excitability in MigraineAltered Excitability in Migraine

Dysfunction of aminergic subcortical projectionsDysfunction of aminergic subcortical projections

Disordered mitochondrial energy metabolismDisordered mitochondrial energy metabolism

Deficiency of systemic and brain MgDeficiency of systemic and brain Mg++++

Abnormal glutamate metabolismAbnormal glutamate metabolism

TGVS=tngemunal vascular sensitization.Adopted from Pietrobon D. Striessing J. Nat Neurosci.2003;4:386-398.

Proposed Mechanisms of MigraineProposed Mechanisms of Migraine

Abnormal cortical Activity:

Hyperexcitable brain (5HT↓, Ca ↑, Glu ↑, Mg ↓)

Abnormal brainstemFunction:

Excitation of brain stem, PAG, etc

Cortical Spreading Depression

Activation/Sensitization of TGVS

Vasodilation; Neurogenic Inflammation

Central Sensitization

Headache Pain

?

Cortical Spreading Depression (CSD)Cortical Spreading Depression (CSD)

Leão AAP, 1914-1993

J Neurophysiol 1944;7:359-390

2 – 3 mm / min2 – 3 mm / min2 – 3 mm / min2 – 3 mm / min

LashleyLashley (1941) (1941): : Spreading auraSpreading auraLashleyLashley (1941) (1941): : Spreading auraSpreading aura

OlesenOlesen (1990) (1990): : Spreading OligemiaSpreading Oligemia

OlesenOlesen (1990) (1990): : Spreading OligemiaSpreading Oligemia

Leão (1944)Leão (1944)::Cortical SpreadingCortical SpreadingDepression (CSD) Depression (CSD)

Leão (1944)Leão (1944)::Cortical SpreadingCortical SpreadingDepression (CSD) Depression (CSD)

Cortical Spreading DepressionCortical Spreading Depression

Milner PM (1958)

Olesen J et al. Ann Neurol. 1990.Olesen J et al. Ann Neurol. 1990.

偏頭痛的腦部血流變化偏頭痛的腦部血流變化 -- -- Spreading OligemiaSpreading Oligemia

Migraine is primarily of neural, not vascular origin.

Cortical Spreading DepressionCortical Spreading Depression in human brainin human brain

Ann Neurol 2001;50:582-587PNAS 2001 (April); 98: 4687-4692

TGVS=tngemunal vascular sensitization.Adopted from Pietrobon D. Striessing J. Nat Neurosci.2003;4:386-398.

Proposed Mechanisms of MigraineProposed Mechanisms of Migraine

Abnormal cortical Activity:

Hyperexcitable brain (5HT↓, Ca ↑, Glu ↑, Mg ↓)

Abnormal brainstemFunction:

Excitation of brain stem, PAG, etc

Cortical Spreading Depression

Activation/Sensitization of TGVS

VasodilationNeurogenic Inflammation

peripheral sensitizationCentral Sensitization

Headache Pain

?

Trigeminal Vascular Activation Trigeminal Vascular Activation

NEJM 2002;346:257-270

Dysfunctioned aminergictransmission (5HT etc.)

& cortical hyperexcitability

Reduced mitochondrialenergy reserve

Excessivemetabolic strain

Biochemical shifts

Spreading depression

TrigeminalVascularactivation

EndogenousPain

Control system

↑5HT transmission

Migraine attack

Proposed Model of MigraineProposed Model of Migraine

Modified from Biomed & Pharmacother 1996;50:71-78

GeneticChannelopathy or Ca ↑, Glu ↑, Mg ↓

Geneticabnormality?

Migraine aura

偏頭痛與遺傳偏頭痛與遺傳 偏頭痛患者有偏頭痛患者有 70%70% 以上亦有家屬罹病以上亦有家屬罹病父母有一人偏頭痛，則小孩罹病率 父母有一人偏頭痛，則小孩罹病率 46%46%父母雙方均偏頭痛，則小孩罹病率 父母雙方均偏頭痛，則小孩罹病率 66%66% 預兆型偏頭痛比無預兆型更易遺傳預兆型偏頭痛比無預兆型更易遺傳 一般常見之偏頭痛則為多重基因遺傳一般常見之偏頭痛則為多重基因遺傳能表現遺傳性偏頭痛之特定基因病變能表現遺傳性偏頭痛之特定基因病變

– FHM-1, FHM-2, FHM-3 FHM-1, FHM-2, FHM-3 家族性偏癱性偏頭痛 家族性偏癱性偏頭痛 (Familial hem(Familial hemiplegic migraine, FHM) iplegic migraine, FHM) 　　

– NOTCH 3 gene NOTCH 3 gene CADASIL (cerebral autosomal dominant arteri CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)opathy with subcortical infarcts and leukoencephalopathy)

– SLC1A3 SLC1A3 EAAT1 (excitatory amino acid transporter 1) glutamat EAAT1 (excitatory amino acid transporter 1) glutamate transportere transporter

Vande Ven RCG. Arch Neurol 2007

Familial Hemiplegic MigraineFamilial Hemiplegic Migraine

Animal Models of Migraine Animal Models of Migraine in the past three decadesin the past three decades

OutlineOutline

Clinical diagnosis and evaluation of Clinical diagnosis and evaluation of migrainemigraine

Pathophysiology of migrainePathophysiology of migraine

Treatment of migraineTreatment of migraine

偏頭痛急性治療偏頭痛急性治療 Triptans Triptans (( 翠普登翠普登 ))

– SumatriptanSumatriptan 50mg po50mg po– Sumatriptan 20mg inSumatriptan 20mg in– Sumatriptan 50mg, 100mg FDT (fast-disintegrating taSumatriptan 50mg, 100mg FDT (fast-disintegrating ta

blet)blet) Ergots Ergots (( 麥角胺麥角胺 ))

– Ergotamine 1mg/caffeine 100mg (eg. Cafergot etc.) 2Ergotamine 1mg/caffeine 100mg (eg. Cafergot etc.) 2# po# po

– Dihydroergotamine 5-10Dihydroergotamine 5-10 mg pomg po

NSAIDs: NSAIDs: ketorolacketorolac 2 mg im/iv, oral NSAIDs2 mg im/iv, oral NSAIDs

OthersOthers– Neuroleptics: Neuroleptics: prochlorperazineprochlorperazine 5-10 mg iv5-10 mg iv– Corticosteroids: Corticosteroids: dexamethasone 5 mg imdexamethasone 5 mg im

偏頭痛急性治療準則偏頭痛急性治療準則儘早用藥，效果確實儘早用藥，效果確實分層治療分層治療

– 輕中度偏頭痛：以非類固醇抗發炎藥物為第一線輕中度偏頭痛：以非類固醇抗發炎藥物為第一線– 中重度偏頭痛：以翠普登或麥角胺為第一線 中重度偏頭痛：以翠普登或麥角胺為第一線

藥物併用，療效更佳，如翠普登併用藥物併用，療效更佳，如翠普登併用 NSAIDNSAID ，或多巴胺拮抗，或多巴胺拮抗劑併用其他急性用藥劑併用其他急性用藥

特殊情形特殊情形– 孕婦或兒童，以單純止痛藥乙醯氨酚為第一線孕婦或兒童，以單純止痛藥乙醯氨酚為第一線– 偏頭痛重積狀態，優先使用類固醇 偏頭痛重積狀態，優先使用類固醇

頻繁使用急性治療，可能導致「藥物過度使用頭痛」頻繁使用急性治療，可能導致「藥物過度使用頭痛」 MedicaMedication Overuse Headache, MOHtion Overuse Headache, MOH

Triptans Triptans 翠普登 翠普登

Agonists for 5-HT Agonists for 5-HT 1B/1D 1B/1D ± 5-HT ± 5-HT 1F1F

11stst triptan: sumatriptan triptan: sumatriptan

22ndnd triptan: zolmi-, nara-, *riza-, *almo-, frova-, *ele- triptan: zolmi-, nara-, *riza-, *almo-, frova-, *ele-– Higher central penetranceHigher central penetrance– *Highest 2h effectiveness with relief within 30-60 min*Highest 2h effectiveness with relief within 30-60 min

Imigran® Imigran® 英明格英明格 (1 tab = sumatriptan 50 mg)(1 tab = sumatriptan 50 mg)

– Onset ~ 40-60 minOnset ~ 40-60 min– Abolish pain ~ 2-4 hrAbolish pain ~ 2-4 hr– Responder rate ~ 70%Responder rate ~ 70%– Also effective for nausea, vomiting photophobia and pAlso effective for nausea, vomiting photophobia and p

honophobiahonophobia

ErgotamineErgotamineNon-selective Agonists for 5-HT Non-selective Agonists for 5-HT 1B/1D 1B/1D ± 5-HT ± 5-HT 1F1F

ergotamine 1mg/caffeine 100mgergotamine 1mg/caffeine 100mg

加非葛加非葛 CafergotCafergot治偏頭痛錠治偏頭痛錠 AntimigraineAntimigraine克痛敏克痛敏 CafegotamineCafegotamine可伏痛可伏痛 CafetonCafeton痛安錠痛安錠 ErgocafeErgocafe易克痛易克痛 ErgotonErgoton麥角咖啡鹼錠麥角咖啡鹼錠 CoffegotCoffegot豐醫痛錠豐醫痛錠 ErgoffeineErgoffeine益汝朗益汝朗 ErgodanErgodan偏痛停偏痛停 MigratinMigratin倍安達倍安達 BaentaBaenta優去痛敏優去痛敏 YuchitonminYuchitonmin痛平定痛平定 TonpenTonpen益可達益可達 ErgolarErgolar益克偏益克偏 ErgofenErgofen麥咖因 麥咖因 Ergocaine Ergocaine

Dihydroergotamine 5mgDihydroergotamine 5mg

塞戈羅塞戈羅 Seglor Seglor (5mg(5mg ；其中；其中 1.1.5mg5mg 為立即釋放劑型、為立即釋放劑型、 3.5mg3.5mg為緩慢釋放劑型為緩慢釋放劑型 ))

道得通道得通 Dihydergot (2.5mg)Dihydergot (2.5mg)樂又適樂又適 Rayosu (1mg)Rayosu (1mg)安得寧安得寧 Antoxine (1.5mg) Antoxine (1.5mg)

Triptans/Ergots for Migraine TreatmentTriptans/Ergots for Migraine Treatment

NEJM 2002;346:257-270

Key Differences Ergots vs. TriptansKey Differences Ergots vs. Triptans

ErgotsErgots TriptansTriptans5-HT5-HT1A1A ++++++++ ++

1B1B ++++++ ++++1D1D ++++++ ++++++

2A2A ++++++ ––2C2C ++++++ ––

AdrenergicAdrenergic

11 ++++++ ––

22 ++++++ ––

DopamineDopamine

DD22 ++++++ ––

DysphoriaDysphoria Nausea / EmesisNausea / Emesis

Anti-migraineAnti-migraine

Peripheral Vascular Peripheral Vascular EffectsEffects

AstheniaAsthenia

DizzinessDizziness

GI / Nausea / EmesisGI / Nausea / Emesis

Triptan/ErgotTriptan/ErgotContraindication and Adverse EventsContraindication and Adverse Events

ContraindicationContraindication– ischemic heart diseaseischemic heart disease– uncontrolled HTNuncontrolled HTN– basilar or hemiplegic migrainebasilar or hemiplegic migraine– pregnancypregnancy– MAO-I useMAO-I use

Adverse EventsAdverse Events– paresthesia, tinglingparesthesia, tingling– flushing, burning, or warm/hot sensationflushing, burning, or warm/hot sensation– dizzy, somnolence, fatigue, heavinessdizzy, somnolence, fatigue, heaviness

偏頭痛預防療法偏頭痛預防療法 AAnti-epileptic drugs (AED)nti-epileptic drugs (AED)

– topiramatetopiramate 、、 valproic acidvalproic acid 、、 gabapentingabapentin BBeta-blockerseta-blockers

– propranololpropranolol 、、 atenololatenolol 、、 nadololnadolol 、、 metoprololmetoprolol CCalcium channel blockersalcium channel blockers

– flunarizineflunarizine 、、 verapamilverapamil Anti-Anti-DDepressantsepressants

– TCA, selective serotonin reuptake inhibitors TCA, selective serotonin reuptake inhibitors

American Association of Neurology, 2000American Association of Neurology, 2000

Mechanism of Migrane PreventativesMechanism of Migrane Preventatives

Glutamate Glutamate NeurotransmissionNeurotransmission

GABA GABA NeurotransmissionNeurotransmission NENE 5-HT5-HT

ββ-Blockers-Blockers

TCAsTCAs

CCBsCCBs

VPAVPA

GBPGBP

TPMTPM

CCBs=calcium channel blockers; VPA=valproate; GBP=gabapentin; TPM=topiramate.

Adapted from Silberstein SD et al. Wolff’s Headache and Other Head Pain. 2001:121-237.

偏頭痛預防療法偏頭痛預防療法採行時機採行時機 每個月頭痛每個月頭痛 3-43-4 次以上或慢性頭痛次以上或慢性頭痛急性藥物無法完全減輕頭痛，或有使用禁忌者急性藥物無法完全減輕頭痛，或有使用禁忌者急性藥物每週使用超過兩次以上急性藥物每週使用超過兩次以上 發作時間超過發作時間超過 4848 小時或發作程度過於嚴重影響生活品質小時或發作程度過於嚴重影響生活品質特殊形式偏頭痛，如併偏癱、過長預兆，或偏頭痛腦梗塞特殊形式偏頭痛，如併偏癱、過長預兆，或偏頭痛腦梗塞施行方式施行方式 每天服藥，一般需持續每天服藥，一般需持續 4-64-6 個月，並於個月，並於 2-32-3週逐漸減藥週逐漸減藥預期效果預期效果 頭痛發生率降低頭痛發生率降低 50+%50+%；急診求診頻次降低 ；急診求診頻次降低 82%82%減少不必要之腦部造影檢查減少不必要之腦部造影檢查 CT 75%CT 75% ，， MRI 88%MRI 88%

TAKE HOME MESSAGESTAKE HOME MESSAGES

Migraine is a prevalent, disabling neurological disease mMigraine is a prevalent, disabling neurological disease more common in female and associated with cardiovasculaore common in female and associated with cardiovascular risksr risks

Hyperexcitability of brain is the pivotal pathomechanism oHyperexcitability of brain is the pivotal pathomechanism of migraine, which may be linked to inherited channelopathf migraine, which may be linked to inherited channelopathy, dysfunctioned amine transmission, and reduced mitochy, dysfunctioned amine transmission, and reduced mitochondrial energy reserveondrial energy reserve

Triptans and ergots are migraine-specific acute treatmentTriptans and ergots are migraine-specific acute treatments, acting by 5HT1b/1d antagonisms, acting by 5HT1b/1d antagonism

Anticonvulsants can prevent migraine probably due to the Anticonvulsants can prevent migraine probably due to the effect of neuro-stabilization after long-term use effect of neuro-stabilization after long-term use