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F
é
d
é
ration
des sciences
neurologiques
du Canada
canadian
neurological
sciences
Federation
The
journal
Canadian Journal of Neurological Sciences
The official Journal of: The Canadian Neurological Society, The Canadian Neurosurgical Society, The
Canadian Society of Clinical Neurophysiologists, The Canadian Association of Child Neurology
PM 40007777 R 9824
AN INTERNATIONAL JOURNAL PUBLISHED BY THE CANADIAN NEUROLOGICAL SCIENCES FEDERATION
Volume 40 Number 5 (Supplement 3) September 2013
Canadian Headache Society Guideline
Acute Drug Therapy for Migraine Headache
A Peer-reviewed SUPPLEMENT to
The Canadian Journal of Neurological Sciences
Suppl. 3 - S1 Canadian Headache Society Guideline: Acute Drug Therapy for Migraine Headache
Suppl. 3 - S4 Introduction to the Guideline, and General Principles of Acute Migraine Management
Section I
Suppl. 3 - S10 Targeted Review: Medications for Acute Migraine Treatment
Section II
Suppl. 3 - S33 Pharmacological Acute Migraine Treatment Strategies: Choosing the Right Drug for a Specific Patient
Section III
Suppl. 3 - S63 Guideline Summary for Primary Care Physicians
Section IV
Suppl. 3 - S69 Guideline Summary for Patients and Their Families
Section V
Suppl. 3 - S73 Guideline Development Summary
Appendix I
Suppl. 3 - S77 Acute Migraine Treatment - Information for Patients
Appendix II
Suppl. 3 - S79 Diary Completion Instructions/Headache Diary
Appendix III
Volume 40 / Number 5 / Supplement 3 / September 2013
F
é
d
é
ration
des sciences
neurologiques
du Canada
canadian
neurological
sciences
Federation
The
journal
Canadian Journal of Neurological Sciences
Irene Worthington1, Tamara Pringsheim3, Marek J. Gawel1,8,9, Jonathan Gladstone1,2, Paul Cooper4,
Esma Dilli5, Michel Aube6, Elizabeth Leroux7, Werner J. Becker3
on behalf of the Canadian Headache Society Acute Migraine Treatment Guideline Development Group
1Sunnybrook Health Sciences Centre, Toronto, Ontario; 2Gladstone Headache Clinic, Toronto, Ontario; 3University of Calgary and the Hotchkiss Brain Institute, Calgary, Alberta;
4University of Western Ontario, London, Ontario; 5University of British Columbia, Vancouver, British Columbia; 6McGill University, Montreal, Quebec, 7University of Montreal,
Montreal, Quebec; 8Rouge Valley Health System – Centenary, Toronto, Ontario; 9Women’s College Hospital, Toronto, Ontario, Canada.
Disclaimer: This guideline is designed to offer evidence-based strategies for the acute treatment of migraine. It is not, however, intended to
replace clinical judgment or establish a treatment protocol for all individuals with migraine. Although every attempt has been made to provide
current information, it is the responsibility of the practitioner to ensure that drugs and dosages are used correctly.
Editor-in-Chief/Rédacteur en chef
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Vivek Mehta EDMONTON, AB
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ISSN 0317 - 1671
Volume 40 / Number 5 / Supplement 3 / September 2013
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The
journal
Canadian Journal of Neurological Sciences
ABSTRACT: Objectives: The primary objective of this guideline is to assist the practitioner in choosing an appropriate acute medication
for an individual with migraine, based on current evidence in the medical literature and expert consensus. It is focused on patients with
episodic migraine (headache on ≤ 14 days a month). Methods: A detailed search strategy was used to find relevant meta-analyses,
systematic reviews and randomized double-blind controlled trials. Recommendations were graded with the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) Working Group, using a consensus group. In addition, a general literature review
and expert consensus were used for aspects of acute therapy for which randomized controlled trials are not available. Results: Twelve
acute medications received a strong recommendation for use in acute migraine therapy (almotriptan, eletriptan, frovatriptan, naratriptan,
rizatriptan, sumatriptan, zolmitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and acetaminophen). Four received a
weak recommendation for use (dihydroergotamine, ergotamine, codeine-containing combination analgesics, and tramadol-containing
combination analgesics). Three of these were NOT recommended for routine use (ergotamine, and codeine- and tramadol-containing
medications). Strong recommendations were made to avoid use of butorphanol and butalbital-containing medications. Metoclopramide
and domperidone were strongly recommended for use where necessary. Our analysis also resulted in the formulation of eight general acute
migraine treatment strategies. These were grouped into: 1) two mild-moderate attack strategies, 2) two moderate-severe attack or NSAID
failure strategies, 3) three refractory migraine strategies, and 4) a vasoconstrictor unresponsive-contraindicated strategy. Additional
strategies were developed for menstrual migraine, migraine during pregnancy, and migraine during lactation. Conclusion: This guideline
provides evidence-based advice on acute pharmacological migraine therapy, and should be helpful to both health professionals and
patients. The available medications have been organized into a series of strategies based on patient clinical features. These strategies may
help practitioners make appropriate acute medication choices for patients with migraine.
RÉSUMÉ: Lignes directrices de la Canadian Headache Society : médicaments pour traiter la crise aiguë de migraine. Objectifs : L’objectif
principal de ces lignes directrices est d’aider le médecin à choisir une médication appropriée pour un individu qui présente des crises aiguës de migraine.
Ces lignes directrices sont basées sur les données actuelles de la littérature médicale et sur un consensus expert. Elles sont ciblées sur les patients qui
souffrent de migraine épisodique (céphalée présente ≤ 14 jours par mois). Méthode : Une stratégie de recherche détaillée a été utilisée pour identifier les
méta-analyses pertinentes, les revues systématiques et les essais contrôlés randomisés, à double insu. Les recommandations ont été classées selon le
Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group au moyen d’un groupe de consensus. De plus, une
revue générale de la littérature et un consensus expert ont été utilisés pour traiter des aspects du traitement de la crise aiguë pour lesquels des essais
contrôlés randomisés ne sont pas disponibles. Résultats : Douze médicaments pour le traitement de la crise aiguë ont reçu une forte recommandation pour
leur utilisation comme traitement de la crise aiguë de migraine (l’almotriptan, l’élétriptan, le frovatriptan, le naratriptan, le rizatriptan, le sumatriptan, le
zolmitriptan, l’ASA, l’ibuprofène, le naproxène sodique, le diclofénac potassique et l’acétaminophène). Quatre ont reçu une faible recommandation pour
leur utilisation (la dihydroergatomine, l’ergotamine, les analgésiques contenant de la codéine et les analgésiques contenant du tramadol). Trois n’étaient
pas recommandés pour utilisation de routine (l’ergotamine et les médicaments contenant de la codéine et ceux contenant du tramadol). Une forte
recommandation a été émise contre l’utilisation du butorphanol et des médicaments contenant du butalbital. La métoclopramide et le dompéridone ont
été fortement recommandés pour utilisation au besoin. Notre analyse a également mené à l’élaboration de huit stratégies générales de traitement. Elles
ont été regroupées ainsi : 1) deux stratégies pour traiter les crises légères ou modérées ; 2) deux stratégies pour traiter les crises modérées ou sévères ou
lors d’un échec du traitement par les AINS ; 3) trois stratégies pour le traitement de la migraine réfractaire et 4) une stratégie pour traiter un patient qui
ne répond pas à un vasoconstricteur ou chez qui une telle médication est contre -indiquée. Des stratégies additionnelles ont été développées pour la
migraine menstruelle, la migraine pendant la grossesse et la migraine pendant la lactation. Conclusion : Ces lignes directrices fournissent des conseils
fondés sur des preuves sur le traitement pharmacologique de la crise aiguë de migraine et devraient être utiles tant aux professionnels de la santé qu’aux
patients. Les médicaments disponibles ont été organisés en une série de stratégies selon le tableau clinique que présente le patient. Ces stratégies peuvent
aider les médecins à choisir une médication appropriée pour traiter les crises aigues chez les patients atteints de migraine.
Can J Neurol Sci. 2013; 40: Suppl. 3 - S1-S3
Suppl. 3 - S1
Canadian Headache Society Guideline:
Acute Drug Therapy for Migraine
Headache
Irene Worthington1, Tamara Pringsheim3, Marek J. Gawel1,8,9,
Jonathan Gladstone1,2, Paul Cooper4, Esma Dilli5, Michel Aube6,
Elizabeth Leroux7, Werner J. Becker3on behalf of the Canadian Headache
Society Acute Migraine Treatment Guideline Development Group
From 1Sunnybrook Health Sciences Centre, Toronto, Ontario; 2Gladstone Headache Clinic, Toronto, Ontario; 3University of Calgary and the Hotchkiss Brain Institute, Calgary,
Alberta; 4University of Western Ontario, London, Ontario; 5University of British Columbia, Vancouver, British Columbia; 6McGill University, Montreal, Quebec, 7University of
Montreal, Montreal, Quebec; 8Rouge Valley Health System – Centenary, Toronto, Ontario; 9Women’s College Hospital, Toronto, Ontario, Canada.
RECEIVED JUNE 9, 2013. FINAL REVISIONS SUBMITTED JUNE 22, 2013.
Correspondence to: W.J. Becker, Division of Neurology, 12th Floor, Foothills Hospital, 1403 29th St NW, Calgary, Alberta, T2N 2T9, Canada.
INTRODUCTION
The Canadian Headache Society Acute Migraine Treatment
Guideline Development Group:
Neurologists: Tamara Pringsheim, W. Jeptha Davenport, Gordon
Mackie, Suzanne N. Christie, Marek Gawel, Michel Aube,
Werner J. Becker, Esma Dilli, Paul Cooper, Rose Giammarco, R.
Allan Purdy, Gordon Robinson, Jonathan Gladstone, Elizabeth
Leroux, Farnaz Amoozegar, Sian Spacey, Viera Saly
Family Physicians: Gary Shapero, Eric Magnoux
Pharmacists: Irene Worthington
Nurses: Irene O’Callaghan, Valerie South
External Reviewers: Joyce Cote (pharmacist) Calgary Chronic
Pain Center and Alberta Health Services, Calgary, Alberta; Lori
Montgomery (Family Physician) University of Calgary and
Alberta Health Services, Calgary, Alberta
Contributions to the Guideline – Authors
Irene Worthington conducted initial and subsequent literature
searches, and was the primary author of Sections 1 and 2. She
contributed to Sections 3, 4, 5, and Appendix 2, participated in
consensus groups, and in the final preparation of the manuscript.
Werner J Becker was the primary author of Sections 3, 4, and
5, and of Appendices 1 and 2. He contributed to Sections 1 and
2 and the final preparation of the manuscript, and participated in
all consensus groups.
Tamara Pringsheim assisted in the literature review, provided
valuable advice for the data analysis, and provided extensive
feedback on the manuscript.
Marek J Gawel provided extensive feedback on the
manuscript and participated in consensus groups.
Jonathan Gladstone provided extensive feedback on the
manuscript and participated in consensus groups.
Paul Cooper provided extensive feedback on the manuscript
and participated in consensus groups.
Esma Dilli provided extensive feedback on the manuscript
and participated in consensus groups (except on sections related
to opioid and barbiturate use).
Michel Aube provided extensive feedback on the manuscript
and participated in consensus groups.
Elizabeth Leroux provided extensive feedback on the
manuscript and participated in consensus groups.
Other members of the Canadian Headache Society Acute
Migraine Treatment Guideline Development Group
Participated in consensus groups and / or provided feedback
on the manuscript.
External Reviewers
We are very grateful to our external reviewers who reviewed
draft manuscripts and provided extensive feedback. They did
not review the final manuscript, and the authors take full
responsibility for the content of this guideline.
Conflicts of Interest
Irene Worthington has served on Advisory Boards and/or
received speaker’s honoraria or educational travel grants from
Merck, Glaxo Smith Kline, Tribute Pharmaceuticals, Pfizer, and
Astra Zeneca.
Tamara Pringsheim has served on advisory boards for Shire
Canada and Merz Canada, and has received a travel award from
Teva Neuroscience.
Marek Gawel has served on advisory boards and / or received
research funding from GlaxoSmithKline, Pfizer Allergan,
Merck, Janssen, Neuraxon, Allergan, Astra Zeneca and Abbott.
Jonathan Gladstone has served on Advisory Boards and/or
been involved with clinical trials for and/or received educational
grants/speaker’s honoraria from: Allergan, Merck, Teva, Johnson
& Johnson and Pfizer. He holds investments in Allergan.
Paul Cooper has served on advisory boards for Allergan.
Esma Dilli has served on advisory boards for Allergan, UCB
and Tribune. She has received speaker’s honoraria from
Allergan, Merck and Johnson and Johnson.
Michel Aubé has served on Advisory boards and / or done
clinical trials for and /or received speaker’s honoraria from:
Merck, Teva, Johnson and Johnson, and Pfizer.
Elizabeth Leroux has served on advisory boards for and / or
received honoraria from Allergan, Merck, Pfizer, and Johnson
and Johnson. Her institution (Hôpital Notre-Dame, Montreal,
QC, Canada) has received grants from Pfizer, Merck, and Teva
Neuroscience.
Werner J Becker has served on Advisory boards and / or done
clinical trials for and /or received speaker’s honoraria from:
Allergan, Merck, AGA Medical, Medtronic, Teva, Johnson and
Johnson, Electrocore, and Pfizer.
R. Allan Purdy has served on medical advisory boards for
Merck and Electrocore.
Gary Shapero has served on advisory boards and / or received
speaker’s honoraria from Merck Frosst, Pfizer, Astra Zeneca,
McNeil, GSK, Teva, Alleregan, and Johnston and Johnston.
Gordon Mackie has served on medical advisory boards and /
or served as a consultant for, received educational travel grants
from or done clinical trials for Allergan, Tribute, Merck, Johnson
and Johnson, Pfizer, Astra Zeneca, and UCI.
Rose Giammarco has served on medical advisory boards, and
/ or received speaker’s honoraria or research funding from
Allergan, Pfizer, Johnson and Johnson, andTeva.
Suzanne Christie has served on Advisory Boards and/or
received Research Grants, Speaker’s Honoraria or Educational
Grants from Merck Frosst, Allergan, Pfizer, Teva, Electrocore,
and Johnson and Johnson.
Sian Spacey has received speaker’s honoraria from Tribute,
Johnson and Johnson and Allergan.
W. Jeptha Davenport, Farnaz Amoozegar, Eric Magnoux,
Gordon Robinson, Viera Saly, Valerie South, Irene O’Callaghan,
Joyce Cote, Lori Montgomery report no conflicts of interest.
This Guideline was produced without external funding or
industry support by the Canadian Headache Society.
THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
Suppl. 3 - S2
Guideline Structure
This guideline is divided into five sections and two
appendices. The targeted review in Section 2 is the core of the
guideline, but Sections 1 and 3 address many other issues
important for acute migraine treatment for which randomized
controlled trial information is not available.
A guideline summary for primary care physicians and a
summary for patients are also provided. Appendix 1 provides a
detailed summary of how the guideline was developed.
Appendix 2 provides a patient information sheet on acute
migraine treatment. Appendix 3 provides a headache diary with
instructions. A headache diary can also be downloaded from
headachenetwork.ca. The sections and appendices are listed
below. Each contains its own references in order to allow it to be
used on its own, and to allow for easier updating:
Section 1: Introduction to the Guideline, and General
Principles of Acute Migraine Management
Section 2: Targeted Review: Medications for Acute Migraine
Treatment
Section 3: Pharmacological Acute Migraine Treatment
Strategies: Choosing the Right Drug for a Specific Patient
Section 4: Acute Drug Therapy for Migraine Headache:
Guideline Summary for Primary Care Physicians
Section 5: Acute Drug Therapy for Migraine Headache:
Guideline Summary for Patients and Their Families
Appendix 1: Guideline Development Summary
Appendix 2: Acute Migraine Treatment: Information for
Patients
Appendix 3: Headache Diary
Disclaimer: This guideline is designed to offer evidence-based
strategies for the acute treatment of migraine. It is not, however,
intended to replace clinical judgment or establish a treatment
protocol for all individuals with migraine. Although every
attempt has been made to provide current information, it is the
responsibility of the practitioner to ensure that drugs and
dosages are used correctly.
Suppl. 3 - S3
LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES
Migraine is a common neurological disorder, which can
produce significant disability, and reduce health-related quality
of life.1,2 Canadian studies have shown migraine prevalence rates
of 23 to 26% in women, and 7.8 to 10% in men.2-4
Over 4,000,000 Canadians suffer from migraine5, and as a
result migraine is associated with a substantial social and
economic impact. A study done in 1990 calculated that 7,000,000
ABSTRACT: Objectives: To provide an overview of the objectives and target population of the guideline, and to review the general
principles of acute pharmacological migraine therapy. Methods: A general literature review and several consensus groups were used to
formulate an expert consensus for the general use of acute migraine medications. Results: The objective of the guideline is to assist the
physician in choosing an appropriate acute migraine medication for an individual with migraine, and thereby to reduce migraine-related
disability. The target population includes adults with episodic migraine (patients with migraine headache < 15 days/month). This
guideline is intended primarily for physicians who treat patients with migraine. Other health professionals may also find this guideline
helpful. Acute migraine therapy should be considered for the great majority of patients with migraine. A specific acute medication is
chosen based on evidence for efficacy, tolerability, migraine attack severity, patient preference, and on the presence of co-existing
disorders. General principles of acute migraine therapy include that the response of a patient to any given medication cannot be predicted
with certainty, and that treatment early in the attack is generally more effective than treatment later once the migraine attack is fully
developed. A suitable treatment approach (stratified or stepped approaches) and drug formulation (injection, tablet, wafer, powdered
formulation, or nasal spray) should be chosen based on patient clinical features. Excessively frequent use of acute medications
(medication overuse) should be avoided. Two or more acute medications can be combined if necessary. Conclusions: This guideline
provides evidence-based advice on the use of acute medications for migraine, and should provide useful guidance for acute migraine
therapy to both health professionals and patients.
RÉSUMÉ: Introduction aux lignes directrices et aux principes généraux du traitement de la crise aiguë de migraine. Objectifs : Le but de cet
article est de fournir un aperçu des objectifs et de la population ciblée par les lignes directrices et de revoir les principes généraux du traitement
pharmacologique de la crise aiguë de migraine. Méthode : Nous avons effectué une revue de littérature et utilisé plusieurs groupes de consensus pour
formuler un consensus expert concernant l’utilisation générale des médicaments pour traiter la crise aiguë de migraine. Résultats : L’objectif des lignes
directrices est d’aider le médecin à choisir un médicament approprié pour traiter la crise aiguë de migraine chez un individu présentant de la migraine
et ainsi diminuer l’invalidité due à la migraine. La population cible est constituée d’adultes présentant de la migraine épisodique (des patients qui
présentent une céphalée migraineuse < 15 jours par mois). Ces lignes directrices sont destinées essentiellement aux médecins qui traitent des patients
migraineux. Les autres professionnels de la santé peuvent également en tirer profit. Le choix du traitement de la crise aiguë de migraine est basé sur
des preuves de son efficacité et de sa tolérabilité, sur la sévérité des crises de migraine, sur les préférences du patient et sur la présence de comorbidités.
Parmi les principes généraux du traitement de la crise aiguë de migraine, il est important de noter que la réponse d’un patient à un médicament particulier
ne peut être prédite avec certitude et que le traitement administré tôt au cours de la crise est généralement plus efficace que le traitement administré
lorsque la crise de migraine est bien installée. Une méthode de traitement convenable (méthode stratifiée ou par étapes) et la formulation du médicament
(injection, comprimé, capsule, poudre ou vaporisation nasale) devraient être choisies en fonction des manifestations cliniques que présente le patient.
Une fréquence excessive d’utilisation de la médication de phase aiguë (surconsommation de médicaments) est à éviter. Deux médicaments ou plus pour
traiter une crise aiguë peuvent être combinés si nécessaire. Conclusions : Ces lignes directrices fournissent des conseils fondés sur des preuves pour
l’utilisation de la médication pour traiter la crise aiguë de migraine et fournissent des conseils utiles sur son traitement, tant pour les professionnels de
la santé que pour les patients.
Can J Neurol Sci. 2013; 40: Suppl. 3 - S4-S9
Suppl. 3 - S4
Introduction to the Guideline, and
General Principles of Acute Migraine
Management
Irene Worthington1, Tamara Pringsheim3, Marek J. Gawel1,8,9,
Jonathan Gladstone1,2, Paul Cooper4, Esma Dilli5, Michel Aube6,
Elizabeth Leroux7, Werner J. Becker3on behalf of the Canadian Headache
Society Acute Migraine Treatment Guideline Development Group
From 1Sunnybrook Health Sciences Centre, Toronto, Ontario; 2Gladstone Headache
Clinic, Toronto, Ontario; 3University of Calgary and the Hotchkiss Brain Institute,
Calgary, Alberta; 4University of Western Ontario, London, Ontario; 5University of
British Columbia, Vancouver, British Columbia; 6McGill University, Montreal,
Quebec, 7University of Montreal, Montreal, Quebec; 8Rouge Valley Health System –
Centenary, Toronto, Ontario; 9Women’s College Hospital, Toronto, Ontario, Canada.
RECEIVED JUNE 9, 2013. FINAL REVISIONS SUBMITTED JUNE 22, 2013.
Correspondence to: W.J. Becker, Division of Neurology, 12th Floor, Foothills Hospital,
1403 29th St NW, Calgary, Alberta, T2N 2T9, Canada.
SECTION I
LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES
Suppl. 3 - S5
workdays were lost annually in Canada due to migraine.4
Disability related to migraine has been recognized by the World
Health Organization, which ranked migraine as 19th among all
causes of disability in terms of years lived with disability.6
The International Headache Society (IHS) has classified two
major subtypes: migraine without aura, and migraine with aura.
Migraine without aura is the most common migraine subtype,
and is characterized by headache attacks lasting 4 to 72 hours.
Headache attacks are usually accompanied by other symptoms
including photophobia, phonophobia, nausea, and sometimes
vomiting (for diagnostic criteria see Tables 1 and 2). Individuals
with migraine with aura experience in addition reversible focal
neurological symptoms, which usually precede the headache and
last up to 60 minutes, or occasionally longer (Table 2).7,8
Acute (symptomatic) pharmacological migraine therapy
refers to the use of medication to treat individual migraine
attacks. The great majority of adults with migraine in Canada
(90%) use acute medications for their migraine attacks.2Acute
medications are, however, only one component of migraine
treatment. Based on headache frequency in population studies, it
would appear that up to 25% of migraine sufferers might also
benefit from the use of daily preventive medications to reduce
migraine frequency.9Pharmacological prophylaxis should be
considered in patients with frequent and/or refractory migraine
attacks. All migraine sufferers should also consider careful
management of lifestyle factors and specific migraine triggers,
which can potentially increase migraine frequency (see
Headache Network Canada website: http://www.headache
network.ca (in English and French), Migraine Quebec website:
www.migrainequebec.com (in French; to be translated into
English), and American Headache Society website:
http://www.americanheadachesociety.org/professionalresources/
TriggerAvoidanceInformation.asp). In addition, behavioural
interventions including the mastery of relaxation techniques,
stress management, pacing, cognitive behavioural therapy, and
biofeedback have the potential to benefit many migraine
sufferers.10-12
Acute pharmacological migraine therapy includes both
“migraine-specific” medications (e.g., triptans, dihydro-
ergotamine), and “non-specific” medications (e.g., ASA,
acetaminophen, NSAIDs). It also includes adjunctive drugs
such as anti-emetics (e.g., domperidone, metoclopramide,
prochlorperazine) in oral or rectal formulations. The introduction
of sumatriptan subcutaneous injection in 1991 represented a
significant advance in the management of migraine. When the
first Canadian migraine guidelines were published in 1997, the
only triptan available was sumatriptan.7Since that time, six more
triptans have become available to Canadians. Although triptans
are generally considered to be the most effective of the acute
migraine medications overall, as recently as 2005, only 8% of
Canadians listed a triptan as their main migraine medication.2
Under-utilization of effective acute therapies has the potential to
negatively impact quality of life for migraine sufferers.
Population-based data in 2005 indicated that at least 200,000
Canadian women with migraine were very unsatisfied with the
effectiveness of their acute migraine medications.2,13
These guidelines have been developed to assist both health
professionals and patients to develop more effective acute
migraine treatment strategies.
Table 1: International Headache Society criteria for
migraine without aura8
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 two of the following characteristics:
- unilateral location
- pulsating quality
- moderate or severe pain intensity
- aggravation by or causing avoidance of routine physical
activity (e.g., walking or climbing stairs)
D. During headache, at least one of the following is present:
- nausea and / or vomiting
- photophobia and phonophobia
E. Not attributed to another disorder
Table 2: International Headache Society criteria for typical
migraine with aura*8
A. At least 2 attacks fulfilling criteria B-D
B. Aura consisting of at least one of the following, but no motor
weakness:
1. fully reversible visual symptoms including positive
features (e.g., flickering lights, spots or lines) and/or negative
features (i.e., loss of vision)
2. fully reversible sensory symptoms including positive
features (i.e., pins and needles) and/or negative features (i.e.,
numbness)
3. fully reversible dysphasic speech disturbance
C. At least two of the following:
1. homonymous visual symptoms and/or unilateral sensory
symptoms
2. at least one aura symptom develops gradually over ≥ 5
minutes and/or different aura symptoms occur in succession
over ≥ 5 minutes
3. each symptom lasts ≥ 5 and ≤ 60 minutes
D. Headache fulfilling criteria B-D for Migraine without aura
begins during the aura or follows aura within 60 minutes
E. Not attributed to another disorder
* Other less common types of migraine with aura include typical aura
with non-migraine headache, typical aura without headache, familial
hemiplegic migraine, and others.
THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
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Guideline Objectives and Target Population
Objectives
The primary objective of this guideline is to assist the
physician in choosing an appropriate acute medication for an
individual with migraine, based on current evidence in the
medical literature. An additional objective is to assist the
practitioner in using the chosen medication in the most effective
manner.
The main clinical question that this guideline aims to help
answer for the medical practitioner is, “Which acute medication
should be prescribed for an individual patient in a specific
clinical situation?”
The ultimate purpose or goal of this guideline is to reduce the
headache-related disability suffered by individuals with
migraine.
Target population
This guideline provides evidence-based recommendations for
the outpatient acute management of adults (18 years-of-age or
older) with episodic migraine (patients who experience migraine
headache attacks on less than 15 days/month). It does not include
recommendations for pediatric patients and for the emergency
room management of acute migraine.
Although it is likely that physicians will extrapolate from the
evidence presented here and use it for the care of patients with
chronic migraine (headache on 15 days a month or more, with
diagnostic criteria for migraine met on at least eight days a
month), many of the clinical trials reviewed for this guideline did
not include patients with headache frequencies of this
magnitude.
Who should use this guideline?
This guideline is intended primarily for physicians who treat
patients with migraine, including both family physicians, and
specialists. Other health professionals who treat patients with
migraine may also find this guideline helpful. As migraine is a
chronic disorder, and it is important that patients with migraine
partner with their health care professionals in order to achieve
the best management success possible, individuals with migraine
and their families may also find this guideline useful.
Expert consensus and recommendations
The core of this guideline is Section 2 “Targeted Review:
Medications for Acute Migraine Treatment”. The
recommendations in this section are based on a targeted review
as described in that section. Evidence from randomized
controlled trials is not available, however, to guide clinicians
with regard to all the clinical decisions that must be made. To
recognize this, treatment suggestions made in other sections of
this guideline are labeled as “expert consensus”, as they are
based on a general literature review and on the expert opinion of
clinicians experienced in migraine treatment. These expert
opinions were developed through expert consensus groups (See
Appendix 1).
Goals of Acute Migraine Therapy
The goals of acute (or symptomatic) migraine therapy are to
relieve pain and the associated symptoms of migraine (e.g.,
nausea, vomiting, photophobia, phonophobia) rapidly and
consistently, with minimal or no adverse events, and to relieve
migraine-related disability so that the patient can return quickly
to normal function.7Although some patients may be able to
achieve the goal of becoming pain-free within two hours of
taking an acute medication, those who only achieve partial
headache relief (pain reduction) should try at least several acute
medications (including several triptans if not contraindicated)
over time for different migraine attacks, to determine if it is
possible for them to reach this goal.
General Principles of Acute Migraine Therapy
1. The response of the individual with migraine to a specific
acute drug cannot be predicted with certainty
Response to acute medications is individual and
idiosyncratic.7If the response to the first medication is not
excellent, several medications may need to be tried (in
succession) over time for different attacks to determine the most
suitable medication in terms of efficacy and tolerability. Access
to two different medications may be necessary if a patient suffers
from attacks of varying severities. The choice of a particular
symptomatic medication should take into account the efficacy of
past treatments, and the presence of any concomitant disorders
that may preclude use of certain medications. For patients with
severe attacks, a rescue medication may be needed if their usual
medication fails.
EXPERT CONSENSUS
i. Several acute medication trials may be necessary before
an appropriate acute medication is found for a specific
patient. Some patients with attacks of varying severity may
need access to more than one medication for successful
migraine management.
ii. A rescue plan should be discussed with patients with
severe migraine attacks whose usual acute medication
does not provide adequate headache relief consistently for
every attack.
2. Early intervention: Most patients should be encouraged to
take their acute medication early in the attack
To experience maximum effectiveness, patients should use
acute medications as early as possible after headache onset, and
while the pain is still mild. For the triptans, several prospective
studies have shown improved efficacy with early treatment (see
Table 6 in Section 2). Triptans may be more effective when taken
early in the attack, because they can prevent but not reverse
central sensitization. Central sensitization, as manifested by
cutaneous allodynia, may occur in up to 75% of patients within
20 to 60 minutes of migraine onset.14
When discussing early treatment, patients should be educated
with regard to the effects of medication overuse, and the need to
differentiate migraine attacks from tension-type headache. For
patients with frequent migraine attacks, early treatment may
need to be used very cautiously. More effective acute treatment
may result in less symptomatic medication use; however,
LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES
Suppl. 3 - S7
indiscriminate use of early treatment has the potential to lead to
acute medication overuse in some patients.15 Patients may find
taking acute medication during the migraine aura useful to
manage their headaches, but for triptans there is evidence that
they are best taken at the onset of head pain rather than during
the aura. This is particularly true for subcutaneous sumatriptan
(see Section 3).
EXPERT CONSENSUS
i. Patients should be advised to take acute medications as
early as possible during their migraine attacks while pain
is still mild, unless at risk for medication overuse
headache.
3. An appropriate treatment approach should be chosen
Three basic treatment strategies have been documented as
options for acute migraine treatment.16 In Section 3 of this
guideline, we use the term “strategy” for acute treatment
paradigms for specific patient groups, based on patient clinical
features. To avoid confusion, we will therefore use the term
“approach” rather than “strategy” for the more broad or
generalized concepts of stratified and step care approaches to
care, while recognizing that these were termed “strategies” in the
original publications that described them:
a. “Stratified care”: The medication chosen for a patient is
based on attack severity and/or degree of migraine-related
disability.17,18
b. “Step care within an attack”: A simple analgesic or
NSAID is used initially for a migraine attack. If the first
medication is not successful, another medication (e.g., a
triptan), is used a few hours later.
c. “Step care across attacks”: The practitioner prescribes an
initial medication (e.g., NSAID), and the patient tries this
for several attacks. If this medication is not sufficiently
effective, the practitioner would prescribe another
medication (e.g., a triptan) for subsequent attacks.
In practice, many patients have tried several non-prescription
medications prior to consulting a physician for their headaches;
therefore, a “step care across attacks” approach is already in
place when the physician prescribes a more effective medication.
“Stratified care” is likely to be the most effective acute
treatment approach, and has been shown to be cost effective.19 It
has been promoted by several guidelines (The U.S. Headache
Consortium20, and the European Federation of Neurological
Societies21,22). Stratified care is the model of care recommended
here for patients with the most severe migraine attacks, while a
modified or “hybrid” model of care, which incorporates features
of both stratified care and the “step care across attacks” model,
is recommended for most patients with migraine in this guideline
(see Section 3). “Step care within an attack” has been promoted
by some guidelines, but it has the disadvantage that if the first
medication fails, the second presumably more effective
medication may fail as well, because it is taken later in the attack
(at a time when it may no longer be as effective as it could have
been if taken earlier). The “step care across attacks” approach
has the potential disadvantage that if the initial medication
provided by the physician is ineffective, patients may become
discouraged and not pursue additional medical care for their
migraine (become a “lapsed consulter”). If this approach is
chosen, patients should be informed early of the remaining
treatment options, so that they realize other therapies are
available for their migraine should that prove necessary.
It needs to be recognized that many patients with migraine
have more than one attack severity. If they are able to identify
early in the attack whether they are going to experience a severe
attack or one of lesser intensity, they may be able to choose an
appropriate medication for their attack based on the stratified
care model. If patients are unable to identify the ultimate severity
of their migraine attack early in its course, a “step care within an
attack” approach may be appropriate if the majority of their
attacks are relatively mild and respond to an NSAID or other
medication, and if their more severe attacks still respond to their
second medication even when taken later in the attack.
EXPERT CONSENSUS
i. When recommending an acute migraine medication,
consideration should be given to attack severity
(“stratified care” approach) and past response to
medications.
ii. If a “step care across attacks” approach is chosen,
patients should be educated with regard to remaining
available treatment options, to reduce the risk of patients
becoming discouraged and no longer consulting for their
headaches.
iii. Although a “step care within an attack” approach may be
suitable for some patients, patients should be advised that
most acute medications are more effective if taken early in
the migraine attack.
4. A suitable medication formulation should be chosen
Patient preference needs to be considered when
recommending a particular medication formulation.23,24
However, some formulations have advantages over others in
specific clinical situations. For some patients, it may be
advantageous to use one formulation for some attacks, and
another formulation for others.
a. For migraine attacks that build up very rapidly and/or are
characterized by early vomiting, and for attacks that
present full-blown upon awakening, an injectable
formulation (e.g., subcutaneous sumatriptan) has the
potential to be most effective.25-27
b. Patients with nausea and those who vomit only later in the
attack may find nasal spray formulations to be more
helpful than oral formulations, as medications delivered
by nasal spray are partially absorbed through the nasal
mucosa.23,24,28,29
c. Patients with lesser degrees of nausea or nausea that is
exacerbated by taking water, and those who wish to treat
their attacks early in situations where water may not be
readily available, may find the orally disintegrating tablets
more useful than regular tablets which are swallowed.
Orally disintegrating tablets do not have a faster onset of
action, as they are not absorbed through the buccal
mucosa, but rather are swallowed with saliva, and
absorbed in gastrointestinal tract.23,24,30
d. For patients without significant nausea, regular oral
THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
Suppl. 3 - S8
tablets, orally disintegrating tablets, nasal sprays and
injections are all appropriate options. The injection
formulation has the greatest efficacy, but higher cost and
more discomfort.26,27 Because of partial nasal absorption,
nasal spray formulations may have a slightly faster onset
of action than tablets.28,29 The evidence for significant
absorption through the nasal mucosa is strongest for
zolmitriptan nasal spray.31,32
e. Some oral formulations are designed for faster drug
delivery and onset of action, as compared to regular oral
tablets. Examples are diclofenac powder for oral solution,
sumatriptan DF (fast dissolving) tablet, and others (e.g.,
effervescent ASA, liquid-containing NSAID preparations).
Patients should be made aware of these options where
appropriate, so that those with migraine attacks that
increase rapidly in intensity can take advantage of these
special formulations if they wish to.
EXPERT CONSENSUS
i. When choosing an acute migraine medication for a
specific patient, consideration should be given to the
clinical features of the attack including rate of increase of
headache intensity and the presence of nausea and / or
vomiting early in the attack, and an appropriate
medication formulation should be chosen. Some patients
may require more than one formulation.
5. Medication overuse needs to be avoided because of the risk
of medication overuse headache
All the commonly used acute medications have the potential
to cause medication overuse headache (MOH) in patients with
migraine when used too frequently over a period of several
months or more.33-35 To avoid MOH, commonly accepted
recommendations are to:
a. Limit use of acetaminophen, ASA, and NSAIDs to a
maximum of 14 days a month.36,37
b. Limit use of triptans, ergotamine, opioids and combination
analgesics to a maximum of 9 days a month.36,37
For patients taking medications from both classes, the
important principle is for the patient to be free of acute
medications at least 20 days a month.36,37 The International
Headache Society (IHS) Diagnostic Criteria indicate that
patients taking both triptans and NSAIDs should limit their use
of these to a total of 9 days a month to avoid risk of MOH
(http://ihs-classification.org/en/01_einleitung/03_anleitung/).
For patients with frequent attacks who are at risk of MOH,
behavioural approaches to migraine management and
prophylactic medications should be considered in addition to
acute medications.
EXPERT CONSENSUS
i. When initiating treatment with acute migraine
medications, the patient should be educated with regard to
medication overuse headache. Patients should avoid use
of ASA, NSAIDs and acetaminophen on more than 14 days
per month, and use of triptans, ergots, opioids, or
combination analgesics on more than 9 days a month.
Patients taking different acute medications on different
days should limit their total use of acute medications to 9
days a month if one of their medications is a triptan, a
combination analgesic, an ergotamine, or an opioid.
ii. Patients should be advised to monitor their acute
medication use if their attacks are frequent, preferably
with a headache diary, in order to reduce the risk of
medication overuse headache.
iii. Pharmacological prophylaxis should be considered for
patients with frequent migraine attacks who may be at risk
of medication overuse.
6. Two or more acute medications can be combined if
necessary
Some patients may obtain better migraine attack relief if they
take two or more acute medications simultaneously for their
migraine attacks. For many patients, triptans satisfactorily treat
migraine related nausea as well as the headache. Others,
however, may benefit from taking an anti-nauseant (e.g.,
metoclopramide 10 mg) with their triptan. Some patients with
attacks that do not respond satisfactorily to a triptan alone may
have better relief if they take an NSAID (e.g., naproxen sodium
550 mg) with their triptan. These acute treatment options are
discussed in more detail in Section 3 of the guideline.
EXPERT CONSENSUS
i. Although a single acute medication may relieve migraine
attacks satisfactorily for many patients, others may benefit
from taking more than one medication simultaneously
(e.g., an NSAID with an anti-nauseant; an anti-nauseant
with a triptan, or a triptan with an NSAID).
Choosing an Acute Migraine Medication
There is no ideal acute migraine medication. Practitioners
should find the principles of acute migraine therapy outlined
above helpful in choosing an acute medication for a specific
patient. Medication cost has not been directly considered in the
recommendations in this guideline, although it is considered to
some extent in the “combined acute medication treatment
approach” in Section 3. In this approach, unless the patient has
severe attacks and fits into the “stratified care” approach, less
expensive NSAIDs are tried before a triptan is chosen (if
necessary) as the patient’s primary acute medication.
In addition, other considerations in choosing an acute
medication for a specific patient include:
1. Efficacy: How strong is the evidence that the drug is
effective in acute migraine therapy and how effective is it
compared to other treatment options?
2. Drug side effect profile: How safe is the drug, and how
well tolerated?
3. Co-existing medical and/or psychiatric disorders: Does the
patient have another disorder that is a contraindication for
some of the acute migraine medications (e.g., a history of
peptic ulcer, or cardiovascular disease)?
4. Patient preference: Section 2 provides information on the
evidence for efficacy and side effects of the various acute
migraine medications. Further guidance in choosing an
acute medication for a specific patient is given in Section
3. A patient survey has indicated that an overwhelming
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Suppl. 3 - S9
majority of patients consider complete relief of head pain,
no recurrence, and rapid onset of action as important or
very important attributes of acute migraine therapy.38
Fortunately, many clinical trials use endpoints relevant to
these preferences, and these are used in this guideline
where possible.
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sequential recruitment of spinal and supraspinal nociceptive
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16. Lipton RB, Stewart WF, Stone AM, Lainez MJ, Sawyer JP,
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42:3-9.
Canadian guidelines for the pharmacological treatment of
migraine were first published in 1997.1At that time, the only
migraine specific medications available were the ergot
derivatives (ergotamine and dihydroergotamine), and the
5-HT1B/1D receptor agonist (triptan), sumatriptan. Since
publication of these guidelines, another six triptans have become
available in Canada. Non-specific acute medications (e.g., ASA,
NSAIDs, and acetaminophen) also have a role in migraine
ABSTRACT: Objective: To assess the evidence base for drugs used for acute treatment of episodic migraine (headache on ≤ 14 days a
month) in Canada. Methods: A detailed search strategy was employed to find relevant published clinical trials of drugs used in Canada
for the acute treatment of migraine in adults. Primarily meta-analyses and systematic reviews were included. Where these were not
available for a drug or were out of date, individual clinical trial reports were utilized. Only double-blind randomized clinical trials with
placebo or active drug controls were included in the analysis. Recommendations and levels of evidence were graded according to the
principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, using a consensus
group. Results: Eighteen acute migraine medications and two adjunctive medications were evaluated. Twelve acute medications
received a strong recommendation with supporting high quality evidence for use in acute migraine therapy (almotriptan, eletriptan,
frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and
acetaminophen). Four acute medications received a weak recommendation for use with low or moderate quality evidence
(dihydroergotamine, ergotamine, codeine-containing combination analgesics, and tramadol-containing combination analgesics). Three
of these medications were NOT recommended for routine use (ergotamine, and codeine- and tramadol-containing medications), and
strong recommendations were made to avoid use of butorphanol and butalbital-containing medications. Both metoclopramide and
domperidone received a strong recommendation for use with acute migraine attack medications where necessary. Conclusion: Our
targeted review formulated recommendations for the available acute medications for migraine treatment according to the GRADE
method. This should be helpful for practitioners who prescribe medications for acute migraine treatment.
RÉSUMÉ: Revue ciblée : les médicaments pour traiter la crise aiguë de migraine. Objectif : Le but de l’étude était d’évaluer les données sur
lesquelles est fondée l’utilisation des médicaments pour le traitement de la crise aiguë de migraine épisodique (céphalée présente ≤ 14 jours par mois)
au Canada. Méthode : Nous avons utilisé une stratégie de recherche détaillée pour identifier les essais cliniques publiés qui étaient pertinents et qui
portaient sur les médicaments utilisés au Canada pour le traitement de la crise aiguë de migraine chez l’adulte. Ce sont principalement des méta-analyses
et des revues systématiques qui ont été utilisées. Seuls les essais cliniques randomisés à double insu, contrôlés par placebo ou médicament actif, ont été
inclus dans l’analyse. Les recommandations et les niveaux de preuve ont été classés selon les principes du Grading of Recommendations Assessment,
Development and Evaluation (GRADE) Working Group, par un groupe de consensus. Résultats : Dix-huit médicaments pour traiter la crise aiguë de
migraine et deux médicaments d’appoint ont été évalués. Douze médicaments ont reçu une forte recommandation fondée sur des données de haute
qualité pour leur utilisation dans le traitement de la crise aiguë de migraine (l’almotriptan, l’élétriptan, le frovatriptan, le naratriptan, le rizatriptan, le
sumatriptan, le zolmigriptan, l’ASA, l’ibuprofène, le naproxène sodique, le diclofénac potassique et l’acétaminophène). Quatre médicaments pour traiter
la crise aiguë de migraine ont reçu une recommandation faible fondée sur des données de qualité faible ou modérée (la dihydroergotamine, l’ergotamine,
les analgésiques contenant de la codéine et les analgésiques contenant du tramadol). Trois de ces médicaments n’étaient pas recommandés pour
utilisation de routine (l’ergotamine et les médicaments contenant de la codéine et les médicaments contenant du tramadol) et des recommandations fortes
ont été émises contre l’utilisation de médicaments contenant du butorphanol et du batalbital. Le métoclopramide et le dompéridone ont reçu une forte
recommandation pour leur utilisation en association avec les médicaments pour traiter les crises aiguës de migraine si nécessaire. Conclusion : Notre
revue ciblée nous a mené a formuler des recommandations selon la méthode GRADE concernant les médicaments disponibles pour traiter la crise aiguë
de migraine. Ceci devrait aider les médecins qui prescrivent des médicaments pour traiter la crise aiguë de migraine.
Can J Neurol Sci. 2013; 40: Suppl. 3 - S10-S32
Suppl. 3 - S10
Targeted Review: Medications for Acute
Migraine Treatment
Irene Worthington1, Tamara Pringsheim3, Marek J. Gawel1,8,9,
Jonathan Gladstone1,2, Paul Cooper4, Esma Dilli5, Michel Aube6,
Elizabeth Leroux7, Werner J. Becker3on behalf of the Canadian Headache
Society Acute Migraine Treatment Guideline Development Group
From 1Sunnybrook Health Sciences Centre, Toronto, Ontario; 2Gladstone Headache
Clinic, Toronto, Ontario; 3University of Calgary and the Hotchkiss Brain Institute,
Calgary, Alberta; 4University of Western Ontario, London, Ontario; 5University of
British Columbia, Vancouver, British Columbia; 6McGill University, Montreal,
Quebec, 7University of Montreal, Montreal, Quebec; 8Rouge Valley Health System –
Centenary, Toronto, Ontario; 9Women’s College Hospital, Toronto, Ontario, Canada.
RECEIVED JUNE 9, 2013. FINAL REVISIONS SUBMITTED JUNE 26, 2013.
Correspondence to: W.J. Becker, Division of Neurology, 12th Floor, Foothills Hospital,
1403 29th St NW, Calgary, Alberta, T2N 2T9, Canada.
SECTION II
LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES
Suppl. 3 - S11
management. The objective of this section of the guideline is to
assess the evidence base for drugs used for acute treatment of
episodic migraine (headache on ≤ 14 days a month) in Canada.
METHODOLOGY
A targeted review of the literature as outlined below was
completed to assess available evidence for acute migraine
medications in adults. Only drugs available in Canada are
included in the guideline. Appendix 1 provides more information
on the development of this guideline. For further details on the
general principles of acute medication use, please see Section 1
of this guideline. Section 3 provides treatment strategies for
choosing a specific acute medication for an individual patient.
Literature Search Strategy
A MEDLINE search of the English language for migraine
disorders and use of triptans, ergotamine, dihydroergotamine,
analgesics, NSAIDs, and antiemetics was performed. Only
randomized, controlled trials (RCTs) and meta-analyses/
systematic reviews of acute migraine medications in adults (18
years-of-age and older) and available in Canada were