No disclosures. Some medications discussed may be used off label.

No disclosures.No disclosures.

Some medications discussed Some medications discussed may be used off label.may be used off label.

No disclosures.No disclosures.

Some medications discussed Some medications discussed may be used off label.may be used off label.

Goals and ObjectivesGoals and ObjectivesGoals and ObjectivesGoals and Objectives

• Review migraine pathophysiologyReview migraine pathophysiology

• Discuss optimal selection and timing of Discuss optimal selection and timing of acute migraine treatmentsacute migraine treatments

• Learn to individualize triptans for Learn to individualize triptans for maximum efficacymaximum efficacy

• Briefly review preventive strategies and Briefly review preventive strategies and optionsoptions

Migraine Diagnostic Criteria: Migraine Diagnostic Criteria:

A) At least 5 attacks fulfilling criteria B–D

B) Headache attacks lasting 4-72 hours (untreated or

unsuccessfully treated)

C) Headache has at least 2 of the following 4 characteristics:

1. unilateral location

2. pulsating quality

3. moderate or severe pain intensity

4. aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs)

D) During headache at least 1 of the following:

1. nausea and/or vomiting

2. photophobia and phonophobia

E) Not better accounted for by another ICHD-3 diagnosis

Migraine EpidemiologyMigraine EpidemiologyMigraine EpidemiologyMigraine Epidemiology

• 18% of adult females18% of adult females• 6% of adult males6% of adult males• 35-45 million migraineurs in the US35-45 million migraineurs in the US• 12% of US population12% of US population• 50% of all neurologic disability50% of all neurologic disability• 2.1 million ED visits/year2.1 million ED visits/year• Economic burden > $20 billion/yearEconomic burden > $20 billion/year

Lipton RB, et al. Headache. 2001.Lipton RB, et al. Headache. 2001.Goldstein JN. Cephalalgia. 2006.Goldstein JN. Cephalalgia. 2006.

http://www.az-tmj.com/treatment-headaches.php

Migraine PathophysiologyMigraine PathophysiologyMigraine PathophysiologyMigraine Pathophysiology

1.1. Activation of neuronal Activation of neuronal ““central generatorcentral generator”” (cortical spreading depression vs. brainstem (cortical spreading depression vs. brainstem origin?) →origin?) →

2.2. Disrupted cortical ion homeostasis, neuronal Disrupted cortical ion homeostasis, neuronal dysfunction, release of neurochemicals →dysfunction, release of neurochemicals →

3.3. Meningeal blood vessel dilation + activation Meningeal blood vessel dilation + activation of trigeminovascular system →of trigeminovascular system →

Migraine PathophysiologyMigraine PathophysiologyMigraine PathophysiologyMigraine Pathophysiology

4.4. Release of vasoactive neuropeptides Release of vasoactive neuropeptides (Calcitonin Gene Related Peptide (Calcitonin Gene Related Peptide (CGRP), Neurokinins, Prostaglandins, (CGRP), Neurokinins, Prostaglandins, Substance P) from activated trigeminal Substance P) from activated trigeminal sensory nerves leads to ssensory nerves leads to sterile terile neurogenic inflammation →neurogenic inflammation →

5.5. Worsening vasodilation, increasing Worsening vasodilation, increasing firing of trigeminal afferents causing firing of trigeminal afferents causing pain intensification →pain intensification →

Migraine PathophysiologyMigraine PathophysiologyMigraine PathophysiologyMigraine Pathophysiology6.6. Trigeminal nociceptive afferents carry pain Trigeminal nociceptive afferents carry pain

signals to trigeminal nucleus caudalis (TNC) signals to trigeminal nucleus caudalis (TNC) for processing and ascent through thalamus for processing and ascent through thalamus to cortex →to cortex →

7.7. Continuous ascending pain signals activate Continuous ascending pain signals activate more neurons leading to associated more neurons leading to associated symptoms such as photo/phonophobia, N/V symptoms such as photo/phonophobia, N/V →→

8.8. Continued TNC firing can become Continued TNC firing can become autonomous, leading to central sensitization autonomous, leading to central sensitization if activated pathways are not stopped →if activated pathways are not stopped →

Standard of Care Goals of Acute Standard of Care Goals of Acute Migraine TreatmentMigraine Treatment

Standard of Care Goals of Acute Standard of Care Goals of Acute Migraine TreatmentMigraine Treatment

1. Treat attacks effectively, rapidly, 1. Treat attacks effectively, rapidly, consistentlyconsistently

2. Restore ability to function2. Restore ability to function3. Minimize need for back-up and rescue meds3. Minimize need for back-up and rescue meds4. Optimize self-care and reduce subsequent 4. Optimize self-care and reduce subsequent

use of resourcesuse of resources5. Provide cost-effective management5. Provide cost-effective management6. Cause minimal or no adverse events6. Cause minimal or no adverse events

American Academy of Neurology / US Headache Consortium Guidelines (Sept American Academy of Neurology / US Headache Consortium Guidelines (Sept 2000; update in progress):2000; update in progress):

http://www.aan.com/professionals/practice/pdfs/gl0087.pdfhttp://www.aan.com/professionals/practice/pdfs/gl0087.pdf

How many days in the last 3 months were you at least 50% disabled by your migraines at work, home, school, or recreational activities?

MIDAS: Migraine Disability Assessment ScaleMigraine Disability Assessment Scale

Courtesy of Dr. Stewart Tepper, MD

MIDAS:MIDAS: Migraine Disability Migraine Disability AssessmentAssessment

MIDAS:MIDAS: Migraine Disability Migraine Disability AssessmentAssessment

• MIDAS Grade I Little to no disability Score 0-5MIDAS Grade I Little to no disability Score 0-5

---> ---> Low or no treatment needsLow or no treatment needs • MIDAS Grade II Mild disability Score 6-10MIDAS Grade II Mild disability Score 6-10

---> ---> Moderate treatment needsModerate treatment needs• MIDAS Grade III Moderate disability Score 11-20MIDAS Grade III Moderate disability Score 11-20

---> ---> High treatment needsHigh treatment needs• MIDAS Grade IV Severe disability Score 21+MIDAS Grade IV Severe disability Score 21+

---> ---> Urgent treatment needsUrgent treatment needs• Useful on initial screening and follow-up visits to assess Useful on initial screening and follow-up visits to assess

level of function and determine if med change is neededlevel of function and determine if med change is needed

MIDAS Questionnaire; Version 3.0, 1997. Innovative Medical Research. Courtesy of Dr. Stewart Tepper, MD

Treatment StrategyTreatment Strategy

Stratified vs. Step Stratified vs. Step Care?Care?

Treatment StrategyTreatment Strategy

Stratified vs. Step Stratified vs. Step Care?Care?

Stratified CareStratified CareStratified CareStratified Care• Treatment selection based on severity of Treatment selection based on severity of

migraine and associated disabilitymigraine and associated disability

• Supported by Class I evidenceSupported by Class I evidence

• Stratified care more cost effectiveStratified care more cost effective

- May lead to initial use of more costly meds, but…- May lead to initial use of more costly meds, but…

- Migraine specific meds lead to significant decrease - Migraine specific meds lead to significant decrease in ED/office visits and in medical procedures in ED/office visits and in medical procedures

Williams, et al. Pharmacoeconomics. 2001Williams, et al. Pharmacoeconomics. 2001

Sculpher, et al. Pharmacoeconomics. 2002Sculpher, et al. Pharmacoeconomics. 2002

Step CareStep CareStep CareStep Care• Treatment escalated within or across attacksTreatment escalated within or across attacks

• If simple analgesics are ineffective, other If simple analgesics are ineffective, other combinations are given later in the same attack or for combinations are given later in the same attack or for future attacksfuture attacks

• Triptans or DHE considered after other Triptans or DHE considered after other ““stepssteps”” have have failed failed

• Step care causes a delay in necessary migraine-Step care causes a delay in necessary migraine-specific administrationspecific administration

• Long process of trial and error; many patients lapse Long process of trial and error; many patients lapse from care untreated = unnecessary pain and from care untreated = unnecessary pain and impairmentimpairment

Disabilities in Strategies of CareDisabilities in Strategies of Care(DISC) Study(DISC) Study

Disabilities in Strategies of CareDisabilities in Strategies of Care(DISC) Study(DISC) Study

• Compared 3 strategies of migraine management over 6 Compared 3 strategies of migraine management over 6 attacksattacks

• Stratification based on disability (stratified care)Stratification based on disability (stratified care)-MIDAS Grade II: aspirin (ASA) + metoclopramide-MIDAS Grade II: aspirin (ASA) + metoclopramide-MIDAS Grade III, IV: triptan (zolmitriptan)-MIDAS Grade III, IV: triptan (zolmitriptan)

• Step care within attacksStep care within attacks-ASA + metoclopramide: Assess response at 2 hours-ASA + metoclopramide: Assess response at 2 hours-Rescue with triptan prn-Rescue with triptan prn

• Step care across attacksStep care across attacks-ASA + metoclopramide -ASA + metoclopramide -Assess response after 3 attacks-Assess response after 3 attacks-Escalate treatment to triptan if ASA + metoclopramide -Escalate treatment to triptan if ASA + metoclopramide fails 2/3 or 3/3 fails 2/3 or 3/3

Lipton RB, et al. JAMA. 2000;284(20):2599-2605.Lipton RB, et al. JAMA. 2000;284(20):2599-2605.Courtesy of Dr. Stewart Tepper, MDCourtesy of Dr. Stewart Tepper, MD

**28

69

55

20

**

Stratified Care Stratified Care vsvs Step Care across 6 attacks: Step Care across 6 attacks: Headache ResolutionHeadache Resolution

53

41

0

20

40

60

80

100

1 hour 2 hours 4 hours

Stratified care

Stepped care across attacks

Attacks (%)Attacks (%)

**

*p<0.001 vs stepped care across attacks*p<0.001 vs stepped care across attacks

Time post-doseTime post-dose

Lipton RB, et al. JAMA. 2000;284(20):2599-2605.Courtesy of Dr. Stewart Tepper, MD

Delay in use of migraine specific meds Delay in use of migraine specific meds wastes time as migraine pathways become wastes time as migraine pathways become

stronger and more refractory…stronger and more refractory…

Delay in use of migraine specific meds Delay in use of migraine specific meds wastes time as migraine pathways become wastes time as migraine pathways become

stronger and more refractory…stronger and more refractory…

Unhindered escalating migraine power and increasing central sensitization

Acetaminophen

Treatment Strategy:Treatment Strategy:Individualize TreatmentIndividualize Treatment

Treatment Strategy:Treatment Strategy:Individualize TreatmentIndividualize Treatment

• MildMild-moderate attacks (MIDAS I-II):-moderate attacks (MIDAS I-II):

1) NSAIDS1) NSAIDS

2) Combination analgesics2) Combination analgesics

• Moderate-severe attacks (MIDAS III-IV) or Moderate-severe attacks (MIDAS III-IV) or poor response to NSAIDS or combo poor response to NSAIDS or combo analgesics in previous attacks:analgesics in previous attacks:

1) Triptans1) Triptans

2) Dihydroergotamine (DHE)2) Dihydroergotamine (DHE)

NSAIDSNSAIDSNSAIDSNSAIDS

• Inhibit arachidonic acid cascade and Inhibit arachidonic acid cascade and trigeminovascular inflammationtrigeminovascular inflammation

• Inhibit dural plasma extravasationInhibit dural plasma extravasation

• Help prevent central sensitizationHelp prevent central sensitization

• Contraindications: significant renal or GI disease, Contraindications: significant renal or GI disease, bleeding disorders, allergiesbleeding disorders, allergies

• Use maximum dose possible for most efficacyUse maximum dose possible for most efficacy

• Evidence based support as a 1st line option for Evidence based support as a 1st line option for mildmild-moderate disability-moderate disability

NSAIDs, Combination Analgesics, and Non-opiate AnalgesicsNSAIDs, Combination Analgesics, and Non-opiate AnalgesicsDrugDrug

http://www.aan.com/http://www.aan.com/professionals/practice/pdfs/professionals/practice/pdfs/

gl0087.pdfgl0087.pdf

Quality of Quality of EvidenceEvidence

Adverse Adverse effectseffects

CommentsComments RoleRole

Ibuprofen Ibuprofen (400-2400 (400-2400 mg)mg)

AA Gastric irritation/Gastric irritation/

discomfort, N/V common. discomfort, N/V common. NSAIDs should not be used NSAIDs should not be used in patients with ulcer or in patients with ulcer or renal dz.renal dz.

First-line for patients First-line for patients with migraine.with migraine.

Naproxen Naproxen (750-1250 (750-1250 mg)mg)

BB

Naproxen Naproxen sodiumsodium (750-1750 mg)(750-1750 mg)

AA

Piroxicam SL Piroxicam SL (40 mg)(40 mg) BB

Pirprofen Pirprofen (400 mg)(400 mg) BB

Tolfenamic acid Tolfenamic acid (200-(200-400 mg)400 mg)

AA

Acetaminophen + Acetaminophen + ASA + caffeineASA + caffeine

(500 mg + 500 mg + (500 mg + 500 mg + 130 mg [2 tablets])130 mg [2 tablets])

AA InfrequentInfrequent Common adverse eventsCommon adverse events

described above anddescribed above and

include insomnia.include insomnia.


IsomethepteneIsometheptene (130- (130-780 mg)780 mg)

Isometheptene + Isometheptene + Acetaminophen + Acetaminophen + Dichloralphenazone Dichloralphenazone (65mg + 325mg + (65mg + 325mg + 100mg) (2-5caps)100mg) (2-5caps)

Isometheptene + Isometheptene + ParacetamolParacetamol(2-6 caps)(2-6 caps)

BB InfrequentInfrequent Drowsiness, dizziness, andDrowsiness, dizziness, and

nausea.nausea.

Consider for patients Consider for patients w/ mild-to-moderatew/ mild-to-moderate

HA.HA.

NSAIDs, Combination Analgesics, and Non-opiate AnalgesicsNSAIDs, Combination Analgesics, and Non-opiate AnalgesicsDrugDrug






Acetaminophen (650-4000 mg)

BB InfrequentInfrequent Well toleratedWell tolerated May be considered May be considered for use in either for use in either pediatric or pregnant pediatric or pregnant patients.patients.

Diclofenac sodium IM Diclofenac sodium IM (75 mg)(75 mg)

BB

Ketoprofen PR Ketoprofen PR (100mg)(100mg)

BB

Ketorolac IMKetorolac IM

(30-60 mg)(30-60 mg)

BB InfrequentInfrequent Drowsiness and nausea Drowsiness and nausea common adverse events. common adverse events. Should not be used w/ renal Should not be used w/ renal and GI diseases.and GI diseases.

Consider for use inConsider for use in

emergency emergency department.department.

Oral Aspirin

(500-1000 mg)

AA OccasionalOccasional Gastric irritation/Gastric irritation/

discomfort, N/V common. discomfort, N/V common. NSAIDs should not be used NSAIDs should not be used in patients with ulcer or in patients with ulcer or renal dz.renal dz.


Diclofenac K*Diclofenac K*

(50-100 mg)(50-100 mg)

BB

FlurbiprofenFlurbiprofen

(100-300 mg)(100-300 mg)

BB

TriptansTriptansTriptansTriptans• 8 Triptans:8 Triptans:

- - SumatriptanSumatriptan: PO (25, 50, 100 mg), SC (4, 6 mg), : PO (25, 50, 100 mg), SC (4, 6 mg), Needle-less SC (6 mg), NS (5, 20 mg)Needle-less SC (6 mg), NS (5, 20 mg)

- - ZolmitriptanZolmitriptan: NS (5 mg), PO (2.5, 5 mg), ODT : NS (5 mg), PO (2.5, 5 mg), ODT (2.5, 5 mg)(2.5, 5 mg)

- - NaratriptanNaratriptan: PO (1, 2.5 mg): PO (1, 2.5 mg)- - RizatriptanRizatriptan: PO (5, 10 mg), ODT (5, 10 mg): PO (5, 10 mg), ODT (5, 10 mg)- - AlmotriptanAlmotriptan: PO (6.25, 12.5 mg): PO (6.25, 12.5 mg)- - FrovatriptanFrovatriptan: PO (2.5 mg): PO (2.5 mg)- - EletriptanEletriptan: PO (20, 40 mg): PO (20, 40 mg)- - Sumatriptan/NaproxenSumatriptan/Naproxen: PO (85/500 mg): PO (85/500 mg)

TriptansTriptansTriptansTriptans

• Group 1:Group 1:- Faster onset, higher - Faster onset, higher

potency, higher potency, higher recurrencerecurrence

--SumatriptanSumatriptan--Sumatriptan/NaproxenSumatriptan/Naproxen--ZolmitriptanZolmitriptan--RizatriptanRizatriptan--AlmotriptanAlmotriptan--EletriptanEletriptan

Rapoport AM, Tepper SJ, et al. CNS Drugs. Rapoport AM, Tepper SJ, et al. CNS Drugs. 2003.2003.

• Group 2:Group 2:- Slower onset, lower - Slower onset, lower

potency, lower potency, lower recurrencerecurrence

--NaratriptanNaratriptan--FrovatriptanFrovatriptan

TriptansTriptansTriptansTriptans• 5-HT1B agonists5-HT1B agonists::

- constrict pain-producing meningeal blood constrict pain-producing meningeal blood vesselsvessels

- also present in brainstem, significance also present in brainstem, significance uncertainuncertain

- preferentially expressed in intracranial preferentially expressed in intracranial extracerebral arteries > periphery (coronary extracerebral arteries > periphery (coronary arteries); coronary vasoconstriction up to 10-arteries); coronary vasoconstriction up to 10-20% may still occur20% may still occur

MaassenVanDenBrink A, et al. Circulation. 1998.MaassenVanDenBrink A, et al. Circulation. 1998.MacIntyre PD, et al. Circulation. 1993MacIntyre PD, et al. Circulation. 1993

TriptansTriptansTriptansTriptans• 5-HT1D agonists5-HT1D agonists::

- presynaptically inhibit trigeminal peptide presynaptically inhibit trigeminal peptide releaserelease

- inhibit central trigeminal nucleus caudalis inhibit central trigeminal nucleus caudalis nociceptive transduction and processingnociceptive transduction and processing

- inhibit nausea/vomiting in nucleus tractus inhibit nausea/vomiting in nucleus tractus solitariuus solitariuus

Tepper SJ, Millson D. Expert Opin Drug Saf. 2003.Tepper SJ, Millson D. Expert Opin Drug Saf. 2003.Tepper SJ. Med Clin North Am. 2001.Tepper SJ. Med Clin North Am. 2001.


• End result:End result:

1)1) Reversal of vasodilation Reversal of vasodilation

2)2) Decrease in neurogenic inflammation Decrease in neurogenic inflammation

3)3) Reduction of central nociceptive signal Reduction of central nociceptive signal transmission to the thalamus and cortextransmission to the thalamus and cortex

4)4) Cessation of ascending cortical pathways Cessation of ascending cortical pathways which lead to photo/phonophobia, N/V, which lead to photo/phonophobia, N/V, central sensitization central sensitization


• Contraindications: Contraindications: - Coronary artery disease- Coronary artery disease- Cerebrovascular disease- Cerebrovascular disease- Peripheral arterial disease- Peripheral arterial disease- Uncontrolled HTN- Uncontrolled HTN- Pregnancy (Category C)- Pregnancy (Category C)- Breastfeeding- Breastfeeding- Renal or hepatic failure- Renal or hepatic failure- Sepsis- Sepsis- Prinz-Metal angina- Prinz-Metal angina- Hemiplegic or basilar-type migraine- Hemiplegic or basilar-type migraine


• Risk factors for arterial diseaseRisk factors for arterial disease

- HTN, obesity, HLP, DM, smoking, premature - HTN, obesity, HLP, DM, smoking, premature CAD family hx (men < 55, women < 65), CAD family hx (men < 55, women < 65), postmenopausal womenpostmenopausal women

- 1 risk factor: ECG and administration of 1st - 1 risk factor: ECG and administration of 1st dose in office suggested in prescribing info. dose in office suggested in prescribing info. >1 Framingham risk factor: further work-up >1 Framingham risk factor: further work-up may be warranted, similar to a preoperative may be warranted, similar to a preoperative evaluation evaluation

Triptans (Serotonin 1B/1D Receptor Agonists )Triptans (Serotonin 1B/1D Receptor Agonists )DrugDrug






Sumatriptan nasal

spray (tested: 1-40 mg) (approved: 5, 10, 20 mg)

AA OccasionalOccasional Adverse events with nasal Adverse events with nasal spray: unpleasant taste, andspray: unpleasant taste, and

flushing. Chest symptoms flushing. Chest symptoms common but true ischemic common but true ischemic events rare. Contraindicated events rare. Contraindicated w/ risk of CAD, basilar or w/ risk of CAD, basilar or hemiplegic migraine, or hemiplegic migraine, or uncontrolled HTN. Based on uncontrolled HTN. Based on post-marketing information, post-marketing information, rare incidences of MI and rare incidences of MI and stroke have been reported. stroke have been reported. Naratriptan is associated Naratriptan is associated with a slower onset of with a slower onset of action and lower recurrence action and lower recurrence rate. Sumatriptan SC is rate. Sumatriptan SC is associated with a very rapid associated with a very rapid onset of action.onset of action.

Moderate-to-severeModerate-to-severe

migraine. Especiallymigraine. Especially

useful when nonoraluseful when nonoral

route is needed.route is needed.

Oral NaratriptanOral Naratriptan

(tested: 1-2.5 mg) (tested: 1-2.5 mg) (approved: 1, 2.5 mg)(approved: 1, 2.5 mg)

AA InfrequentInfrequent Moderate-to-severeModerate-to-severe

migraine.migraine.

Oral Rizatriptan Oral Rizatriptan (tested: 5-40 mg) (tested: 5-40 mg) (approved: 5, 10 mg)(approved: 5, 10 mg)

AA OccasionalOccasional

Oral Sumatriptan*Oral Sumatriptan*

(tested: 25-100 mg) (tested: 25-100 mg) (approved: 25, 50 mg)(approved: 25, 50 mg)


Oral ZolmitriptanOral Zolmitriptan

(tested: 1-25 mg)(tested: 1-25 mg)

(approved: 2.5, 5 mg)(approved: 2.5, 5 mg)


Sumatriptan SC Sumatriptan SC (tested: 1-8 mg) (tested: 1-8 mg) (approved: 6 mg)(approved: 6 mg)

AA FrequentFrequent Moderate-to-severeModerate-to-severe

migraine. Especiallymigraine. Especially

useful when nonoraluseful when nonoral

route is needed.route is needed.

TriptansTriptansTriptansTriptans• Vary in:Vary in:

- lipophilicity- lipophilicity- bioavailability- bioavailability- time to maximum plasma concentration (Tmax)- time to maximum plasma concentration (Tmax)- peak plasma concentrations (Cmax)- peak plasma concentrations (Cmax)- half-life (t1/2)- half-life (t1/2)- AUC- AUC- metabolismmetabolism- elimination routes- elimination routes- formulations- formulations- drug-drug interaction profiles- drug-drug interaction profiles- side effects- side effects

Rapoport AM, Tepper SJ, et al. CNS Drugs. 2003.Rapoport AM, Tepper SJ, et al. CNS Drugs. 2003.

Rapoport AM, Tepper SJ, Rapoport AM, Tepper SJ, Bigal ME, Sheftell FD. 2003Bigal ME, Sheftell FD. 2003 RouteRoute TmaxTmax T(1/2)T(1/2) MetabolismMetabolism

SumatriptanSumatriptan SCSC 0.17-0.20.17-0.2 22 Hepatic (MAO-A), Hepatic (MAO-A), renalrenal

NSNS 11 22

POPO 2.52.5 22

PRPR 2.52.5 22

Sumatriptan / Sumatriptan / NaproxenNaproxen

POPO S: 1S: 1

N: 5N: 5S: 2S: 2

N: 19N: 19

Hepatic (MAO-A), Hepatic (MAO-A), renalrenal

ZolmitriptanZolmitriptan POPO 22 2.72.7 Hepatic(MAO-A/Hepatic(MAO-A/CYP) CYP)

ODTODT 33 2.5-32.5-3

NSNS 44 33

RizatriptanRizatriptan POPO 1.21.2 22 Hepatic(MAO-A), Hepatic(MAO-A), renalrenal

ODTODT 1.6-2.51.6-2.5 22

AlmotriptanAlmotriptan POPO 1.4-3.81.4-3.8 3.2-3.73.2-3.7 Hepatic(MAO-A/Hepatic(MAO-A/CYP), renalCYP), renal

EletriptanEletriptan POPO 1-21-2 3.6-5.53.6-5.5 Hepatic(CYP3A4)Hepatic(CYP3A4)

NaratriptanNaratriptan POPO 2-32-3 5-6*5-6* Hepatic(CYP), Hepatic(CYP), renalrenal

FrovatriptanFrovatriptan POPO 2-42-4 2626 Hepatic(CYP), Hepatic(CYP), renalrenal

Does it matter which triptan I Does it matter which triptan I pick??pick??

Does it matter which triptan I Does it matter which triptan I pick??pick??

Choose based on patient and migraine characteristicsChoose based on patient and migraine characteristics Choose based on patient and migraine characteristicsChoose based on patient and migraine characteristics

CComorbiditiesomorbidities

OOnset to peak migraine painnset to peak migraine pain

RRecurrence of migraine after ecurrence of migraine after treatment (within 24 hours?)treatment (within 24 hours?)

NNausea and vomiting severityausea and vomiting severity

Which Triptan Do I Pick?Which Triptan Do I Pick?Which Triptan Do I Pick?Which Triptan Do I Pick?

CORNCORN

CComorbiditiesomorbiditiesCComorbiditiesomorbidities

- Coronary artery disease- Coronary artery disease- Cerebrovascular disease- Cerebrovascular disease- Peripheral arterial disease- Peripheral arterial disease- Uncontrolled HTN- Uncontrolled HTN- Pregnancy (Category C)- Pregnancy (Category C)- Breastfeeding- Breastfeeding- Renal or hepatic failure- Renal or hepatic failure- Sepsis- Sepsis- Prinz-Metal angina- Prinz-Metal angina- Hemiplegic or basilar-type migraine- Hemiplegic or basilar-type migraine

OOnsetnset to migraine peak painto migraine peak painOOnsetnset to migraine peak painto migraine peak pain

• Group 1 (quicker onset) vs. Group 2 (slower Group 1 (quicker onset) vs. Group 2 (slower onset)onset)

-In general, response rates for group 2 triptans at 4 -In general, response rates for group 2 triptans at 4 hrs are similar to response rates for group 1 hrs are similar to response rates for group 1 triptans at 2 hrstriptans at 2 hrs

Tepper SJ, Spears RC. Neurol Clin. 2009.Tepper SJ, Spears RC. Neurol Clin. 2009.

• Subcutaneous injection or nasal spray form of Subcutaneous injection or nasal spray form of triptan needed if:triptan needed if:

- Patient wakes with migraine- Patient wakes with migraine

- Peak pain within 30 minutes- Peak pain within 30 minutes

RReturn of migraine after treatmenteturn of migraine after treatmentRReturn of migraine after treatmenteturn of migraine after treatment

• If migraine recurrence occurs within 24 If migraine recurrence occurs within 24 hours:hours:

- Combine triptan with NSAID- Combine triptan with NSAID

-Try a group 2 triptan (Naratriptan vs. -Try a group 2 triptan (Naratriptan vs. Frovatriptan)Frovatriptan)

NNauseaausea and vomiting severityand vomiting severityNNauseaausea and vomiting severityand vomiting severity

• If N/V occur early in the attack or are If N/V occur early in the attack or are severe:severe:

- A subcutaneous injection or nasal spray - A subcutaneous injection or nasal spray form of triptan should be usedform of triptan should be used

- *- *RememberRemember: dissolvable tablets are still : dissolvable tablets are still absorbed via GI tract, not sublinguallyabsorbed via GI tract, not sublingually

Triptan PearlsTriptan PearlsTriptan PearlsTriptan Pearls• Sumatriptan:Sumatriptan:- Highest potency (SC) and quickest onset (SC+NS) - Highest potency (SC) and quickest onset (SC+NS)

of all triptansof all triptans- Greatest flexibility- Greatest flexibility

• Rizatriptan:Rizatriptan:- Fastest onset of an - Fastest onset of an oraloral triptan triptan- Greatest likelihood of 2h pain-free and sustained - Greatest likelihood of 2h pain-free and sustained

pain-free responsepain-free response- Propranolol increases its serum concentration so - Propranolol increases its serum concentration so

Rizatriptan should be no more than 5mg per dose Rizatriptan should be no more than 5mg per dose if used togetherif used together

Rapoport AM, Tepper SJ, et al. CNS Drugs. 2003.Rapoport AM, Tepper SJ, et al. CNS Drugs. 2003.Rapoport AM, Tepper SJ. Arch Neurol. 2001.Rapoport AM, Tepper SJ. Arch Neurol. 2001.

Triptan PearlsTriptan PearlsTriptan PearlsTriptan Pearls• Zolmitriptan: Zolmitriptan: - Most likely to treat persistent HA when 1st dose - Most likely to treat persistent HA when 1st dose

failsfails

• Almotriptan:Almotriptan:- Group 1 triptan w/ least side effects- Group 1 triptan w/ least side effects

• Eletriptan:Eletriptan:- Highest potential for drug interactions. Decrease - Highest potential for drug interactions. Decrease

dosage w/ CyP3A4 drugs such as macrolides, dosage w/ CyP3A4 drugs such as macrolides, fungal, HIV, etc.fungal, HIV, etc.


Triptan PearlsTriptan PearlsTriptan PearlsTriptan Pearls

• Naratriptan: Naratriptan: - The "gentle triptan", least side effects- The "gentle triptan", least side effects

- Slower onset of action, but lowest recurrence - Slower onset of action, but lowest recurrence raterate

- Does not have monoamine oxidase - Does not have monoamine oxidase metabolism, so can be given w/ MAOI (as can metabolism, so can be given w/ MAOI (as can Eletriptan and Frovatriptan)Eletriptan and Frovatriptan)


Triptan PearlsTriptan PearlsTriptan PearlsTriptan Pearls

• FrovatriptanFrovatriptan- Slower onset of action, longest half - Slower onset of action, longest half

life, and lowest range of 24h HA life, and lowest range of 24h HA recurrence compared with placeborecurrence compared with placebo

- Good choice to give night prior to - Good choice to give night prior to expected migraine and known trigger expected migraine and known trigger (menstruation, travel, etc.)(menstruation, travel, etc.)


Triptan PearlsTriptan PearlsTriptan + NSAID CombinationTriptan + NSAID Combination

Triptan PearlsTriptan PearlsTriptan + NSAID CombinationTriptan + NSAID Combination

• Studies show Studies show increased efficacyincreased efficacy and and reduced reduced recurrencerecurrence for sumatriptan and rizatriptan + for sumatriptan and rizatriptan + NSAID and rizatriptan + COX-2 inhibitorsNSAID and rizatriptan + COX-2 inhibitors

Krymchantowski A. Krymchantowski A. Cephalalalgia Cephalalalgia 2001;21:425-426.2001;21:425-426.Krymchantowski AV, Barbosa JS. Krymchantowski AV, Barbosa JS. CephalalgiaCephalalgia 2002; 22:309–312. 2002; 22:309–312.Krymchantowski AV, Bigal ME. Krymchantowski AV, Bigal ME. BMC Neurol BMC Neurol 2004; 28; 4(1):10.2004; 28; 4(1):10.

• Sumatriptan/Naproxen combination pill:Sumatriptan/Naproxen combination pill:- Faster Sumatriptan Tmax for combination pill vs.

Sumatriptan 100 mg alone (1h vs. 1.5 hrs)- Cmax for Naproxen is 36% lower with combination

pill vs. Naproxen 550 mg alone- Tmax for Naproxen occurs 4 hrs later with

combination pill vs. Naproxen 550 mg alone (5h vs. 1-2h)

http://us.gsk.com/products/assets/us_treximet.pdf

Sumatriptan + Naproxen Sodium Combination Sumatriptan + Naproxen Sodium Combination Tablet: Pain Relief at 2 and 4 hoursTablet: Pain Relief at 2 and 4 hoursSumatriptan + Naproxen Sodium Combination Sumatriptan + Naproxen Sodium Combination Tablet: Pain Relief at 2 and 4 hoursTablet: Pain Relief at 2 and 4 hours

6153

44

28

75

64

54

37

0

20

40

60

80

2 Hours 4 Hours

Combo (n=726)

Sumatriptan 85 mg

(n=724)

Naproxen Sodium (n=720)

Placebo (N=742)

*P<0.05 Combination vs placebo, sumatriptan, and naproxen sodium

Pooled results from two head-to-head, randomized, double-blind, placebo-controlled trials, MT-301 and MT-302 of a single moderate or severe migraine attack. Individual study results were similar.

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Brandes et al. JAMA 2007;297:1443-1454Courtesy of Dr. Stewart Tepper, MD

*

*

ErgotsErgotsErgotsErgots• Dihydroergotamine (DHE), ErgotamineDihydroergotamine (DHE), Ergotamine

• Broader spectrum of receptors than triptans: Broader spectrum of receptors than triptans: - additional side effects, but… additional efficacy in some - additional side effects, but… additional efficacy in some

patients (1/3rd of patients respond poorly to triptans)patients (1/3rd of patients respond poorly to triptans)

• Interact with adrenergic and dopaminergic receptors, 5-HT Interact with adrenergic and dopaminergic receptors, 5-HT 1A, 1A, 1B*1B*, , 1D*1D*, , 1F*1F*, 2A, 2C, 3, 4 subtypes, 2A, 2C, 3, 4 subtypes(*RED = Triptan receptors)(*RED = Triptan receptors)

• Side effect profiles reflect agonist activity at:Side effect profiles reflect agonist activity at:- 5-HT1A receptors: nausea, dysphoria- 5-HT1A receptors: nausea, dysphoria- 5-HT2A and adrenergic receptors: peripheral - 5-HT2A and adrenergic receptors: peripheral

vasoconstrictionvasoconstriction- Dopamine D2 receptors: nausea, vomiting- Dopamine D2 receptors: nausea, vomiting

Bigal ME, Tepper SJ. Curr Pain Headache Rep. 2003Bigal ME, Tepper SJ. Curr Pain Headache Rep. 2003Silberstein SD, McRory DC. Headache. 2003Silberstein SD, McRory DC. Headache. 2003

Dihydroergotamine (DHE)Dihydroergotamine (DHE)Dihydroergotamine (DHE)Dihydroergotamine (DHE)

• Intravenous (IV), Subcutaneous (SC), Intravenous (IV), Subcutaneous (SC), Intramuscular (IM), Intranasal (IN) forms; Intramuscular (IM), Intranasal (IN) forms; (Inhaled DHE coming soon)(Inhaled DHE coming soon)

• IV DHE is very useful to break status IV DHE is very useful to break status migrainosusmigrainosus

• No triptan use in pre or post 24 hours of DHENo triptan use in pre or post 24 hours of DHE

• Contraindications same as triptans except Contraindications same as triptans except pregnancy is Category Xpregnancy is Category X

IV DHEIV DHEIV DHEIV DHE1. +/- EKG if concern for CAD risk1. +/- EKG if concern for CAD risk

2. IV Antiemetic +/- IV Diphenhydramine 30 mins prior to IV 2. IV Antiemetic +/- IV Diphenhydramine 30 mins prior to IV DHE (1 mg/1 mL)DHE (1 mg/1 mL)

3. 0.25 mg IV (virgin) vs. 0.50 mg IV. 3. 0.25 mg IV (virgin) vs. 0.50 mg IV. Then, 0.25 mg q15 mins Then, 0.25 mg q15 mins until 1 of the following: until 1 of the following: a) HA resolvesa) HA resolvesb) Severe nausea or other intolerable side effects occurb) Severe nausea or other intolerable side effects occurc) Cumulative dose of 1 mg reachedc) Cumulative dose of 1 mg reached

4. Repeat max tolerated dose (up to 1 mg) q8h with IV 4. Repeat max tolerated dose (up to 1 mg) q8h with IV Antiemetic +/- IV Diphenhydramine 30 mins prior to IV DHEAntiemetic +/- IV Diphenhydramine 30 mins prior to IV DHE

5. AAN Practice Parameter Guidelines suggest IV DHE is safe 5. AAN Practice Parameter Guidelines suggest IV DHE is safe and effective up to 3 mg/day and 20 mg/week (packaging and effective up to 3 mg/day and 20 mg/week (packaging says 6 mg/week)says 6 mg/week)

IM / SC DHEIM / SC DHEIM / SC DHEIM / SC DHE

• 1 mg (1 ml) at onset of migraine 1 mg (1 ml) at onset of migraine

• Then, q1h x 2 for a max dose of 3 mg/attack, Then, q1h x 2 for a max dose of 3 mg/attack, OROR

• Once every 8 hours x 3-5 days or until HA free Once every 8 hours x 3-5 days or until HA free x 24 hrsx 24 hrs

• IM and SC DHE are limited to 3 mg/day and 20 IM and SC DHE are limited to 3 mg/day and 20 mg/week (packaging says 6 mg/week)mg/week (packaging says 6 mg/week)

IN DHEIN DHEIN DHEIN DHE• Insert in nostril, aim away from face, don't sniffInsert in nostril, aim away from face, don't sniff

• 1 spray in each nostril (0.5 mg each nostril = 1 mg total 1 spray in each nostril (0.5 mg each nostril = 1 mg total dose)dose)

• In 15 minutes, repeat 1 spray in each nostril (0.5 mg each In 15 minutes, repeat 1 spray in each nostril (0.5 mg each nostril = 1 mg total dose)nostril = 1 mg total dose)

• Total treatment dose: 4 sprays = 2 mg; May repeat this Total treatment dose: 4 sprays = 2 mg; May repeat this cycle q8h x 72h or until HA is resolved (whichever comes cycle q8h x 72h or until HA is resolved (whichever comes first)first)

• Per packaging, max dose: 4 mg/attack, 6 sprays/day and Per packaging, max dose: 4 mg/attack, 6 sprays/day and 8 sprays/week. (As above, we often use higher doses)8 sprays/week. (As above, we often use higher doses)

When do I consider DHE?When do I consider DHE?When do I consider DHE?When do I consider DHE?

• Long migraines with multiple recurrences, Long migraines with multiple recurrences, including menstrually-related migrainesincluding menstrually-related migraines

• Migraine upon awakening, as its central Migraine upon awakening, as its central effects may reverse central sensitization effects may reverse central sensitization less responsive to triptansless responsive to triptans

• Can be used at moderate to severe levels of Can be used at moderate to severe levels of pain, in the presence of allodynia, when pain, in the presence of allodynia, when triptans are less effectivetriptans are less effective

Baron EP, Tepper SJ. Headache. 2010.Baron EP, Tepper SJ. Headache. 2010.

When do I consider DHE?When do I consider DHE?When do I consider DHE?When do I consider DHE?• Can be used repetitively to break status Can be used repetitively to break status

migrainosis (migraine lasting > 72 hours)migrainosis (migraine lasting > 72 hours)

• Repetitively for rescueRepetitively for rescue

• Repetitively as a bridge to wean a patient out Repetitively as a bridge to wean a patient out of medication overuse headacheof medication overuse headache

• With nausea and vomiting, when a non-oral With nausea and vomiting, when a non-oral alternative is necessaryalternative is necessary

Baron EP, Tepper SJ. Headache. 2010.Baron EP, Tepper SJ. Headache. 2010.

Ergot Alkaloids and DerivativesErgot Alkaloids and Derivatives

DrugDrughttp://www.aan.com/http://www.aan.com/

professionals/practice/pdfs/professionals/practice/pdfs/gl0087.pdfgl0087.pdf




DHE SC (tested: 1mg)

(approved: 1 mg)

BB OccasionalOccasional Most common adverseMost common adverse

events with DHE includeevents with DHE include

nausea, vomiting,nausea, vomiting,

dysphoria, flushing,dysphoria, flushing,

restlessness, and anxiety.restlessness, and anxiety.

Should not be used inShould not be used in

patients at risk for ischemicpatients at risk for ischemic

heart disease. Treatmentheart disease. Treatment

associated with low associated with low recurrence rates. DHErecurrence rates. DHE

SC/IM has considerableSC/IM has considerable

less adverse events than IV.less adverse events than IV.

Use in patients withUse in patients with

moderate-to-severemoderate-to-severe

migraine.migraine.DHE IM (tested: 1 mg) BB OccasionalOccasional

DHE IV (tested: 1-2

mg)

BB FrequentFrequent

DHE IV plus

antiemetics (0.5-1 mg DHE)

BB FrequentFrequent Useful in patients w/ Useful in patients w/ long-standing HA. long-standing HA. May be used as May be used as therapy of choice in therapy of choice in ED.ED.

DHE nasal spray

(tested: 0.5-4 mg)

(approved: 2 mg)

AA OccasionalOccasional Common adverse events: Common adverse events: nasal congestion, N/V. nasal congestion, N/V. Should not be used inShould not be used in

patients with risk of CAD.patients with risk of CAD.

Associated with lowAssociated with low

incidence of recurrence.incidence of recurrence.

Moderate-to-severe Moderate-to-severe HA. TreatmentHA. Treatment

option for patients w/option for patients w/

nausea and/or nausea and/or vomiting.vomiting.

Ergot Alkaloids and DerivativesErgot Alkaloids and Derivatives

DrugDrughttp://www.aan.com/http://www.aan.com/

professionals/practice/pdfs/professionals/practice/pdfs/gl0087.pdfgl0087.pdf




Oral Ergotamine

(tested: 1-5 mg)

(approved: 2 mg)

BB FrequentFrequent Nausea and vomitingNausea and vomiting

common adverse events.common adverse events.

Treatment may beTreatment may be

associated with ischemia,associated with ischemia,

ergotism, and rebound.ergotism, and rebound.

Consider for selectedConsider for selected

patients with patients with moderate to severemoderate to severe

migraine.migraine.

Ergotamine plus

caffeine (tested:

2-6 mg ergotamine +

200-600 mg caffeine)

(approved: 2 mg

ergotamine + 200 mg

caffeine)

BB FrequentFrequent

Ergostine plus

caffeine (tested:

2 mg + 200 mg)

BB FrequentFrequent

Acute Treatment Key PointsAcute Treatment Key PointsAcute Treatment Key PointsAcute Treatment Key Points• Begin Begin APPROPRIATEAPPROPRIATE medication at medication at

APPROPRIATEAPPROPRIATE dose at dose at EARLIESTEARLIEST (<30 mins) sign (<30 mins) sign of migraine painof migraine pain

Cady R, et al. Headache. 2000.Cady R, et al. Headache. 2000.Cady R, et al. Clin Ther. 2000.Cady R, et al. Clin Ther. 2000.Pascual J, et al. Headache. 2000.Pascual J, et al. Headache. 2000.Dowson A, et al. Headache. 2004.Dowson A, et al. Headache. 2004.Diener H, et al. Neurology. 2004.Diener H, et al. Neurology. 2004.Hu X, et al. Headache. 2002.Hu X, et al. Headache. 2002.Mathew N, et al. Headache. 2004.Mathew N, et al. Headache. 2004.Klapper J, et al. Cephalalgia. 2004.Klapper J, et al. Cephalalgia. 2004.Cady R, et al. Curr Med Res Opin. 2004.Cady R, et al. Curr Med Res Opin. 2004.

• Limited to no roleLimited to no role for butalbital-containing for butalbital-containing analgesics or opiates/opioids as 1st line acute analgesics or opiates/opioids as 1st line acute migraine therapymigraine therapy

• Goals should be pain free in 2 hours and 24 hour Goals should be pain free in 2 hours and 24 hour pain reliefpain relief

RESCUERESCUERESCUERESCUE

RESCUERESCUE(Also contraindications to triptans, ergots, NSAIDs; or (Also contraindications to triptans, ergots, NSAIDs; or

adjunctive therapy)adjunctive therapy)

RESCUERESCUE(Also contraindications to triptans, ergots, NSAIDs; or (Also contraindications to triptans, ergots, NSAIDs; or

adjunctive therapy)adjunctive therapy)

• AntiemeticsAntiemetics- Prochlorperazine 10 mg IV, Metoclopramide 10mg IV, - Prochlorperazine 10 mg IV, Metoclopramide 10mg IV,

Dolasetron 12.5 mg IV, Ondansetron 4 mg IV, Dolasetron 12.5 mg IV, Ondansetron 4 mg IV, Granisetron 1 mg IV, Promethazine 25 mg IVGranisetron 1 mg IV, Promethazine 25 mg IV

http://www.aan.com/professionals/practice/pdfs/gl0087.pdfhttp://www.aan.com/professionals/practice/pdfs/gl0087.pdf

• AnticonvulsantsAnticonvulsants- Valproic acid 500-1000 mg IV, Levetiracetam 250-1000 mg - Valproic acid 500-1000 mg IV, Levetiracetam 250-1000 mg

IVIVMatchar DB, et al.Matchar DB, et al.

http://www.aan.com/professionals/practice/pdfs/gl0087.pdfhttp://www.aan.com/professionals/practice/pdfs/gl0087.pdfEdwards, et al. Cephalalgia. 1999.Edwards, et al. Cephalalgia. 1999.Edwards, et al. Headache. 2001.Edwards, et al. Headache. 2001.Mathew, et al. Cephalalgia. 1999.Mathew, et al. Cephalalgia. 1999.

• MagnesiumMagnesium- 1-2 g IV; may be more effective for migraine with auraBigal, et al. Cephalalgia. 2002.Cete, et al. Cephalalgia. 2005.

RESCUERESCUERESCUERESCUE• NSAIDSNSAIDS- Ketorolac 30 mg IV; 60 mg IM; 10 mg PO TID with food until HA - Ketorolac 30 mg IV; 60 mg IM; 10 mg PO TID with food until HA

free x 24 hours, or have used for 5 days.free x 24 hours, or have used for 5 days.

• SteroidsSteroids- Dexamethasone 4-6 mg IV; 4 mg PO TID day 1, then 4 mg PO

BID day 2, then 4 mg PO day 3; Methylprednisolone 250-500 mg IV

Klapper JA, et al. Headache. 1991.Saper JR. Neurol Clin. 1989.

• Muscle RelaxersMuscle Relaxers- Methocarbamol 1-2 g IV; Chlorzoxazone 500-1000 mg qid x 5

days

• NeurolepticsNeuroleptics (other than antiemetics) can also be useful (other than antiemetics) can also be useful- Olanzapine, Quetiapine, Haloperidol*- Olanzapine, Quetiapine, Haloperidol**Fisher H. J Emerg Med. 1995.*Fisher H. J Emerg Med. 1995.

““DirtyDirty”” Rescue: Rescue: Butalbital combos and Butalbital combos and

Opiates/OpioidsOpiates/Opioids

““DirtyDirty”” Rescue: Rescue: Butalbital combos and Butalbital combos and


• No class I studies exist showing efficacy No class I studies exist showing efficacy of barbiturates / butalbital-containing of barbiturates / butalbital-containing meds in acute migraine treatmentmeds in acute migraine treatment

• Both butalbital combos and Both butalbital combos and opiates/opioids pose a high risk of MOH opiates/opioids pose a high risk of MOH (Rebound HA), dependency and are best (Rebound HA), dependency and are best avoidedavoided

Rescue:Rescue: Butalbital combos and Butalbital combos and


Rescue:Rescue: Butalbital combos and Butalbital combos and

Opiates/OpioidsOpiates/Opioids• Limited role for opiate/opioid use in acute Limited role for opiate/opioid use in acute

migraine treatment:migraine treatment:

- Occasionally when abortives have failed- Occasionally when abortives have failed

- When abortives are contraindicated- When abortives are contraindicated-Allergy-Allergy-Pregnancy-Pregnancy-Breastfeeding-Breastfeeding-Other medical contraindications-Other medical contraindications

Summary: Acute Therapies for Migraine (2000)Group 1:Group 1:

Proven pronounced Proven pronounced statistical and clinical statistical and clinical benefit (at least 2 double-benefit (at least 2 double-blind, placebo-controlledblind, placebo-controlled

studies + clinical studies + clinical impression of effect)impression of effect)

Group 2:Group 2:

Moderate statistical and Moderate statistical and clinical benefit (1 double-clinical benefit (1 double-blind, placebo-controlled blind, placebo-controlled study + clinical study + clinical impression of effect)impression of effect)

Group 3:Group 3:

Statistically but not Statistically but not proven clinically proven clinically OROR

clinically but not proven clinically but not proven statistically effective statistically effective (conflicting or (conflicting or inconsistent evidence)inconsistent evidence)

Group 4:Group 4:

Proven to be Proven to be statistically or statistically or clinically ineffective clinically ineffective (failed efficacy vs.(failed efficacy vs.

placebo)placebo)

Group 5:Group 5:

Clinical and statistical Clinical and statistical benefits unknownbenefits unknown

(insufficient evidence(insufficient evidence

available)available)

-Acetaminophen + ASA + Caffeine PO

-ASA PO

-DHE SC, IM, IV*

-DHE IV + antiemetic

-DHE IN

-Ibuprofen PO

-Naproxen sodium PO

-Naratriptan PO

-Prochlorperazine IV

-Rizatriptan PO

-Sumatriptan SC, IN, PO

-Zolmitriptan PO

-Butorphanol IN

************Almotriptan, Frovatriptan, Eletriptan, Sumatrip/Naproxen all released after these guidelines, but should be included.

-Acetaminophen + Codeine PO

-Butalbital + ASA +

Caffeine + Codeine PO

-Butorphanol IM

-Chlorpromazine IM, IV

-Diclofenac K, PO

-Ergotamine + Caffeine + Pentobarbital +

Belafolline® PO

-Flurbiprofen, PO

-Isometheptene compound, PO

-Ketorolac IM

-Lidocaine IN

-Meperidine IM, IV

-Methadone IM

-Metoclopramide IV

-Naproxen PO

-Prochlorperazine IM, PR

-Butalbital + ASA +

Caffeine PO

-Ergotamine PO

-Ergotamine + Caffeine PO

-Metoclopramide IM, PR

-Acetaminophen PO

-Chlorpromazine IM

-Granisetron IV

-Lidocaine IV

-Dexamethasone IV

-Hydrocortisone IV

http://www.aan.com/http://www.aan.com/professionals/practice/professionals/practice/pdfs/gl0087.pdfpdfs/gl0087.pdf

**Final Word on Acute Treatments****Final Word on Acute Treatments****Final Word on Acute Treatments****Final Word on Acute Treatments**

• Guard against medication-overuse headache (MOH; rebound HA). Causes of MOH:

1) NSAIDS or Triptans: > 10 days/month

2) Opioids: > 8 days/month

3) Butalbital compounds > 5 days/month

Bigal ME, Lipton RB. Overuse of acute migraine medications and migraine

chronification. Curr Pain Headache Rep. 2009 Aug;13(4):301-7.

Prevention in Prevention in EpisodicEpisodic Migraine… Migraine…Prevention in Prevention in EpisodicEpisodic Migraine… Migraine…

• Medication use: 1. Initiate meds with the highest level of evidence-based

efficacy.

2. Initiate therapy with the lowest effective dose. Increase slowly until clinical benefits are achieved in the absence of, or until limited by, adverse events.

3. Give each drug an adequate trial (2 to 3 months).

4. Avoid interfering medications (e.g., overuse of acute medications).

5. Use of a long-acting formulation may improve compliance.

http://www.neurology.org/content/55/6/754.full.pdf


• Evaluation:

1. Monitor the patient’s headache through a headache diary +/- MIDAS: Migraine Disability Assessment Scale)

2. Re-evaluate therapy. If after 3 to 6 months headaches are well controlled, consider tapering or discontinuing treatment.



• Take coexisting conditions into account (stroke, CAD, Raynaud’s, epilepsy, mood disorders, weight, etc).

1. Select a drug that will treat the coexistent condition and migraine, if possible.

2. Establish that the treatments being used for migraine are not contraindicated for the coexistent disease.

3. Establish that the treatments being used for coexistent conditions do not exacerbate migraine.

4. Beware of all drug interactions.


2012 AHS/AAN

Guidelines for Prevention

of Episodic Migraine

Level A: established as effective for prevention

Level A: established as effective for prevention

• Anticonvulsants:

-Divalproex/sodium valproate: 400-1000 mg/day (FDA approved)

-Topiramate 25-200 mg/day (FDA approved)

• Antihypertensives:

-Metoprolol: 47.5-200 mg/day

-Propranolol 120-240 mg/day (FDA approved)

-Timolol 10-15 mg/day (FDA approved)

• Complementary:

-Petasites (butterbur): 50-75 bid

Level B: probably effective as prevention

Level B: probably effective as prevention

• Antidepressants:

-Amitriptyline: 25-150 mg/day

-Venlafaxine ER: 150 mg/day


-Atenolol: 100 mg/day

• Complementary:

-Magnesium: 600 mg trimagnesium dicitrate qd

-Feverfew: 50-300 mg bid; 2.08-18.75 mg tid for MIG-99 preparation

-Riboflavin: 400 mg/day

-Histamine: 1-10 ng subcutaneously twice a week

• NSAIDs:

-Fenoprofen: 200-600 mg tid

-Ibuprofen: 200 mg bid

-Ketoprofen: 50 mg tid

-Naproxen: 500-1100 mg/day

-Naproxen sodium: 550 mg bid

Level C: possibly effective for prevention

Level C: possibly effective for prevention


-Candesartan: 16 mg/day

-Lisinopril: 10-20 mg/day

-Nebivolol: 5 mg/day

-Pindolol: 10 mg/day

-Clonidine: 0.75-0.15 mg/day; patch formulations also studied

-Guanfacine: 0.5-1 mg/day

• Anticonvulsants:

-Carbamazepine: 600 mg/day

• Complementary:

-Coenzyme Q10: 100 mg tid

• Antihistamines:

-Cyproheptadine: 4 mg/day

• NSAIDs:

-Flurbiprofen: 200 mg/day

-Mefenamic acid: 500 mg tid

ChronicChronic Migraine MigraineChronicChronic Migraine Migraine

• Chronic migraine: Chronic migraine: - ≥ ≥ 15 days/month with HA lasting ≥ 4 15 days/month with HA lasting ≥ 4

hours/day for ≥ 3 consecutive months in hours/day for ≥ 3 consecutive months in people with current or prior diagnosis of people with current or prior diagnosis of episodic migraine. episodic migraine.

• Onabotulinum Toxin Type A (Botox)Onabotulinum Toxin Type A (Botox)- OnlyOnly FDA-approved treatment of FDA-approved treatment of chronicchronic

migraine (approved for ≥ age 18).migraine (approved for ≥ age 18).- Useful when other preventives fail or are Useful when other preventives fail or are

contraindicatedcontraindicated

ConclusionConclusionConclusionConclusion

• General Principles of Acute Migraine General Principles of Acute Migraine ManagementManagement

1.1. Educate pts about migraine, its treatment and Educate pts about migraine, its treatment and encourage participation in management encourage participation in management (triggers, HA diaries to determine need for (triggers, HA diaries to determine need for prevention, etc.).prevention, etc.).

2.2. Use migraine specific meds (triptans, DHE) Use migraine specific meds (triptans, DHE) earlyearly with moderate-severe migraine and those with moderate-severe migraine and those poorly responsive to NSAIDS or combination poorly responsive to NSAIDS or combination analgesics.analgesics.

ConclusionConclusionConclusionConclusion3.3. Tailor triptan use based on patient Tailor triptan use based on patient and migraine characteristics (and migraine characteristics (CORNCORN). ). →→

4.4. Consider a self-administered rescue med for Consider a self-administered rescue med for severe migraine failing all other treatments.severe migraine failing all other treatments.

5.5. Guard against medication-overuse headache Guard against medication-overuse headache (MOH; rebound HA). (MOH; rebound HA). Causes of MOH:Causes of MOH:

-NSAIDS or triptans: > 10 days/month-NSAIDS or triptans: > 10 days/month-Opioids: > 8 days/month-Opioids: > 8 days/month-Butalbital compounds > 5 days/month-Butalbital compounds > 5 days/month

6. 6. Preventives should target other comorbidities, Preventives should target other comorbidities, at same time of decreasing overall HA burden.at same time of decreasing overall HA burden.

No disclosures. Some medications discussed may be used off label.

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