The 2012 AHS/AAN Guidelines for Prevention of Episodic
Migraine: A Summary and Comparison With Other Recent
Clinical Practice Guidelineshead_2185930..945
Elizabeth Loder, MD, MPH; Rebecca Burch, MD; Paul Rizzoli, MD
Background.—Updated guidelines for the preventive treatment of episodic migraine have been issued by the American
Headache Society (AHS) and the American Academy of Neurology (AAN).We summarize key 2012 guideline recommenda-
tions and changes from previous guidelines.We review the characteristics, methods, consistency, and quality of the AHS/AAN
guidelines in comparison with recently issued guidelines from other specialty societies.
Methods.—To accomplish this,we reviewed theAHS/AAN guidelines and identified comparable recent guidelines through
a systematic MEDLINE search.We extracted key data, and summarized and compared the key recommendations and assessed
quality using the Appraisal of Guidelines Research and Evaluation-II (AGREE-II) tool. We identified 2 additional recent
guidelines for migraine prevention from the Canadian Headache Society and the European Federation of Neurological
Societies.All of the guidelines used structured methods to locate evidence and linked recommendations with assessment of the
evidence, but they varied in the methods used to derive recommendations from that evidence.
Results.—Overall, the 3 guidelines were consistent in their recommendations of treatments for first-line use. All rated
topiramate, divalproex/sodium valproate, propranolol, and metoprolol as having the highest level of evidence. In contrast,
recommendations diverged substantially for gabapentin and feverfew. The overall quality of the guidelines ranged from 2 to 6
out of 7 on the AGREE-II tool.
Conclusion.—The AHS/AAN and Canadian guidelines are recommended for use on the basis of the AGREE-II quality
assessment.Recommendations for the future development of clinical practice guidelines in migraine are provided.In particular,
efforts should be made to ensure that guidelines are regularly updated and that guideline developers strive to locate and
incorporate unpublished clinical trial evidence.
Key words: migraine, guidelines, prevention, prophylaxis, quality, AGREE-II
The American Headache Society (AHS) and the
updated guidelines for pharmacologic preventive
treatment of episodic migraine.1,2Migraine is a
common, disabling, and costly disorder. There is
no cure, but preventive treatment to decrease the
number and severity of headache attacks improves
health outcomes and quality of life.3It also reduces
disability and costs.4
From the Graham Headache Center and the Department of
Neurology, Division of Headache and Pain, Brigham and
Women’s and Faulkner Hospitals, Boston, MA, USA (E.
Loder, R. Burch, P. Rizzoli).
Address all correspondence to E. Loder, Department of Neu-
rology, Brigham and Women’s Hospital, 1153 Centre Street,
Boston, MA 02130, USA, email: email@example.com
To download a podcast featuring further discussion of this
article, please visit www.headachejournal.org
Accepted for publication April 23, 2012.
Conflict of Interest: PR and RB have no conflicts of interest
relevant to this paper. EL is a member of the dissemination
committee for the 2012 AHS/AAN Guidelines but was not
involved in their development. She is the president-elect of
the American Headache Society, which was a partner in the
development of the guidelines and endorsed the completed
Financial support for work: None.
Published by Wiley Periodicals, Inc.
© 2012 American Headache Society
The AHS/AAN guidelines are the result of a
systematic search, expert review, and synthesis of rel-
evant evidence for preventive treatments of episodic
migraine. The evidence identified in formulating the
previous guidelines in 2000 was supplemented with
evidence from a new search that extended through
Despite the availability of such up-to-date,
evidence-based recommendations, research suggests
that a majority of migraine sufferers who would
benefit from prevention therapies do not receive
them.5,6Possible barriers to the adequate preventive
treatment of migraine may be lack of physician
awareness of the contents of clinical practice guide-
lines or a lack of confidence in the methodology and
quality of such guidelines.7-9Variability in guideline
quality and consistency has been demonstrated in
other therapeutic areas.10-12One recent study on clini-
cal practice guideline quality concluded that the
quality of clinical practice guidelines improved only
slightly over the past 2 decades.13
We sought to summarize the key recommenda-
tions of the 2012 AHS/AAN guidelines and identify
areas of change from the 2000 guidelines that they
replace. In addition, we systematically review the
quality and consistency of these guidelines in com-
parison with 2 other recent migraine prevention
clinical practice guidelines.
All authors read the 2012 AHS/AAN guidelines
for migraine prevention, and EL summarized key
concepts and changes from the 2000 guidelines.These
were reviewed with PR and RB, and agreement on
the summary was reached by consensus. Although
these guidelines were published as 2 separate papers,
1 covering traditional pharmacologic agents for
non-steroidal anti-inflammatory drugs (NSAIDs),
complementary treatments and other miscellaneous
treatments, for the purposes of this review, we
consider the guidelines as a whole and refer to the
contents of the 2 documents as “the AHS/AAN
guidelines.”Although the 2012 guidelines incorporate
drugs used for short-term prophylaxis of menstrually
triggered migraine attacks among the other treat-
ments,for this review,we consider them separately to
facilitate comparison with other guidelines, which
generally do not consider such short-term treatments
to be comparable with daily,long-duration preventive
An additional caveat, conspicuous by its absence
from the guidelines presented here is onabotulinum-
toxinA. OnabotulinumtoxinA has been extensively
studied for treatment of episodic migraine and found
to be ineffective. It was not included in the current
AHS/AAN guidelines for preventive treatment of
episodic migraine because it is covered in another
AAN guideline, where it is identified as ineffective
for episodic migraine. OnabotulinumtoxinA was,
tion for the treatment of chronic migraine in October
2010, and at this writing is the only treatment specifi-
cally indicated for that migraine variant.Its exclusion
reflects simply that the guidelines we review and sum-
marize pertain to the treatment of episodic migraine
(ie, migraine with a headache burden of <15 days/
ment would be timely (and clinically relevant) but lies
beyond the scope of the present paper.
For the systematic review portion of this study,we
searched for clinical practice guidelines for the pre-
ventive treatment of migraine in adults 18 or older.
We included only guidelines based on a systematic
review and synthesis of evidence, and graded recom-
mendations linked to evidence quality. Guidelines
had to be written in English and endorsed by a
national or international professional organization.
We excluded guidelines that focused solely on the
treatment of specific subgroups of migraineurs,
eg, pregnant women or children. To ensure that the
clinical practice guidelines included in this review are
relevant to contemporary medical practice, inclusion
was limited to guidelines published from January
2008 through April 2012.
We searched MEDLINE from January 2008 to
April 2012 using the text words and Medical Subject
Heading terms of “migraine” and “guidelines.” The
electronic database search was supplemented by
searching websites that list guidelines. The search
strategy is contained inAppendix II.EL screened the
search results for inclusion. Full-text papers were
retrieved for potentially relevant clinical practice
guidelines and reviewed against inclusion criteria.
The included clinical practice guidelines were sum-
marized descriptively by EL and reviewed by RB
according to pharmacologic and other preventive
treatment options. For each treatment, we noted
whether the respective guideline recommended
that treatment, the level of evidence assigned to it,
and the appraised quality of studies supporting the
We compared treatment ratings among the
included guidelines. Because each guideline used dif-
ferent methods to rate and assign treatments to cat-
egories, we assumed that the top tier in each rating
system was comparable with the top tier in the other
guidelines,and so on.Thus,LevelA in theAHS/AAN
guidelines was considered equivalent to the “High”
level of evidence category in the Canadian guidelines
(regardless of the strength of the recommendation to
use or not use, which was based on judgments about
the balance of harms to benefits) and the “drugs of
first choice”category in European Federation of Neu-
rological Societies (EFNS). Similarly, Level B was
considered equivalent to the“Moderate”level of evi-
dence category in the Canadian guidelines and the
“drugs of second choice”category in the EFNS guide-
considered equivalent to the “Low” level of evidence
category in the Canadian guidelines and to the“drugs
of third choice” category in the EFNS guidelines.
All authors independently scored retrieved
guidelines according to the Appraisal of Guidelines
for Research and Evaluation (AGREE) II criteria.
The AGREE criteria are widely used to assess the
quality of clinical practice guidelines.They provide a
list of specific information that should be reported
in guideline publications. Specifically, the AGREE-II
assessment instrument contains 23 items distributed
among 6 quality domains, along with 2 global quality
The 6 domains and the guideline characteristics
assessed within each domain are: (1) Scope and
Purpose, which assesses the overall aim of the guide-
line and target groups for whom the guideline is
intended; (2) Stakeholder Involvement, which evalu-
ates the extent to which appropriate stakeholders
were involved in developing the guideline and
whether it represents the views of its intended users;
(3) Rigor of Development, which appraises the
process of gathering and summarizing the evidence
and methods used to develop recommendations; (4)
Clarity of Presentation,which evaluates the language,
structure, and format of the guideline; (5) Applicabil-
ity, which evaluates potential barriers and facilitators
to implementation and strategies to improve uptake
as well as resources needed to implement the guide-
line;and (6) Editorial Independence,which evaluates
biases because of competing interests. The overall
assessment includes rating the overall quality of the
guideline and stating whether the guideline is recom-
mended for use in practice.
Each item within a domain is rated on a 7-point
scale ranging from 1 (strongly disagree) to 7 (strongly
agree). A score of 1 indicates that there is no infor-
mation on that item or that it is very poorly reported.
A score of 7 indicates that criteria for the item delin-
eated in the AGREE-II user manual have been met
and that the reporting is complete and clear.A quality
score for each of the 6 domains is calculated, in
addition to a global assessment of overall guideline
quality and recommendations for clinical use. The
AGREE-II developers recommend that guideline
quality should be assessed by 2-4 reviewers.
Summary of AHS/AAN Migraine Prevention
Guideline Recommendations.—Tables 1–3 summa-
rize key recommendations of the AHS/AAN 2012
guidelines for preventive treatment of migraine. The
new guidelines assign treatments to 1 of 5 levels based
on the strength of evidence for their efficacy:LevelA,
Level B,Level C,Level U,and an“Other”group.The
last contains drugs that are established as,or probably
or possibly ineffective. This method of categorizing
treatments is based entirely on assessments of the
strength of scientific evidence of drug efficacy and
does not incorporate evidence about side effects or
qualitative clinical impressions.
ments in the 2000 guidelines.15In the 2000 guidelines,
indicating the highest level of recommendation and
1. Holland S, Silberstein SD, Freitag F, Dodick DW,
NSAIDs and other complementary treatments for
episodic migraine prevention in adults. Neurology.
2. Silberstein SD, Holland S, Freitag F, Dodick DW,
Argoff C. Evidence-based guideline update: Phar-
macologic treatment for episodic migraine preven-
tion in adults. Neurology. 2012;78:1337-1345.
3. D’Amico D, Solari A, Usai S, et al. Improvement in
quality of life and activity limitations in migraine
patients after prophylaxis. A prospective longitudi-
nal multicentre study. Cephalalgia. 2006;26:691-696.
4. Brown JS,Papadopoulos G,Neumann PJ,Friedman
M, Miller JD, Menzin J. Cost-effectiveness of
topiramate in migraine prevention: Results from a
pharmacoeconomic model of topiramate treatment.
5. Lipton RB, Bigal ME, Diamond M, et al. Migraine
prevalence,disease burden,and the need for preven-
tive therapy. Neurology. 2007;68:343-349.
6. Diamond S, Bigal ME, Silberstein S, Loder E,
Reed M,Lipton RB.Patterns of diagnosis and acute
and preventive treatment for migraine in the United
States: Results from the American Migraine Preva-
lence and Prevention study. Headache. 2007;47:355-
7. Oxman AD, Glasziou P, Williams JW Jr. What
should clinicians do when faced with conflicting
recommendations? BMJ. 2008;337:a2530.
8. Rouse C. Patient and practitioner noncompliance:
Rationing, therapeutic uncertainty, and the missing
conversation. Anthropol Med. 2010;17:187-200.
9. Mottur-Pilson C, Snow V, Bartlett K. Physician
explanations for failing to comply with “best prac-
tices. Eff Clin Pract. 2001;4:207-213.
10. Burda BU, Norris SL, Holmer HK, Ogden LA,
Smith ME. Quality varies across clinical practice
guidelines for mammography screening in women
aged 40-49 years as assessed by AGREE and
AMSTAR instruments. J Clin Epidemiol. 2011;64:
11. Cates JR,Young DN,Bowerman DS,Porter RC.An
independent AGREE evaluation of the Occupa-
tional Medicine Practice Guidelines.Spine J.2006;6:
12. Nagy E, Watine J, Bunting PS, et al. Do guidelines
for the diagnosis and monitoring of diabetes mellitus
fulfill the criteria of evidence-based guideline devel-
opment? Clin Chem. 2008;54:1872-1882.
13. Alonso-Coello P,Irfan A,Sola I,et al.The quality of
clinical practice guidelines over the last two decades:
A systematic review of guideline appraisal studies.
Qual Saf Health Care. 2010;19:e58.
14. Brouwers MC, Kho ME, Browman GP, et al.
AGREE II: Advancing guideline development,
reporting and evaluation in health care. J Clin
15. Silberstein SD. Practice parameter: Evidence-based
guidelines for migraine headache (an evidence-
based review):Report of the Quality Standards Sub-
committee of theAmericanAcademy of Neurology.
16. Vedula SS, Bero L, Scherer RW, Dickersin K.
Outcome reporting in industry-sponsored trials of
gabapentin for off-label use. N Engl J Med. 2009;
17. Demarin V, Vukovic V, Lovrencic-Huzjan A,
et al.Evidence based guidelines for the treatment of
primary headaches. Acta Med Croatica. 2008;62:99-
18. Treatment Guideline Subcommittee of the Taiwan
Headache Society.Treatment guidelines for preven-
tive treatment of migraine. Acta Neurol Taiwan.
19. Ravishankar K, Chakravarty A, Chowdhury D,
Shukla R, Singh S. Guidelines on the diagnosis
and the current management of headache and
related disorders. Ann Indian Acad Neurol. 2011;
20. Canadian Headache Society Prophylactic Guide-
lines Development Group. Canadian headache
society guideline for migraine prophylaxis. Can J
Neurol Sci. 2012;39(2 Suppl. 2):1-62.
21. Evers S, Afra J, Frese A, et al. EFNS guideline on
EFNS task force. Eur J Neurol. 2009;16:968-981.
22. Tfelt-Hansen P, Bjarnason NH, Dahlof C, et al.
Evaluation and registration of adverse events in
clinical drug trials in migraine. Cephalalgia. 2008;28:
23. Tfelt-Hansen P,Pascual J,Ramadan N,et al.Guide-
lines for controlled trials of drugs in migraine:Third
edition. A guide for investigators. Cephalalgia.
24. Ioannidis JP. Adverse events in randomized trials:
Neglected, restricted, distorted, and silenced. Arch
Intern Med. 2009;169:1737-1739.
25. McCrory D. Report on gabapentin (Neurontin®)
for migraine prophylaxis: Evaluation of efficacy,
effectiveness and marketing. Expert consultant’s
report. Available at: http://dida.library.ucsf.edu/pdf/
oxx18q10 (accessed April 12, 2012).
26. Loder E. Menstrual migraine: Timing is everything.
27. Chan AW. Out of sight but not out of mind: How to
search for unpublished clinical trial evidence. BMJ.
28. Wieseler B, Kerekes MF, Vervoelgyi V, McGauran
N, Kaiser T. Impact of document type on reporting
quality of clinical drug trials: A comparison of reg-
istry reports, clinical study reports, and journal pub-
lications. BMJ. 2012;344:d8141.
Understanding why evidence from randomised
clinical trials may not be retrieved from Medline:
Comparison of indexed and non-indexed records.
30. Lehman R,Loder E.Missing clinical trial data.BMJ.
31. Tfelt-Hansen P. Subcutaneous sumatriptan: Results
of a peculiar, unpublished, comparative, double-
blind, randomised, and controlled trial. J Headache
32. Tfelt-Hansen PC. Published and not fully published
double-blind,randomised,controlled trials with oral
naratriptan in the treatment of migraine: A review
based on the GSK Trial Register. J Headache Pain.
33. Tfelt-Hansen PC. Unpublished clinical trials with
sumatriptan. Lancet. 2009;374:1501-1502.
34. Hart B,Lundh A,Bero L.Effect of reporting bias on
meta-analyses of drug trials: Reanalysis of meta-
analyses. BMJ. 2012;344:d7202.
Additional Supporting Information may be found in
the online version of this article:
Table 1. AHS/AAN Migraine Prevention Guide-
lines Drugs Recommended for Use.
Table 2. AHS/AAN Migraine Prevention Guide-
lines, Drugs Recommended for Short-Term Prevention
of Migraine Associated With Menstruation.
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material) should be directed to the corresponding
author for the article.