Drug Safety Alert
Drug Safety Alert
Drug Safety Alert
May 6, 2013, the U.S. Food and Drug Administration (FDA) advised health care professionals and
women that the anti-seizure medication valproate sodium and related products, valproic acid and
divalproex sodium, are contraindicated and should not be taken by pregnant women for the prevention
of migraine headaches. Based on information from a recent study, there is evidence that these
medications can cause decreased IQ scores in children whose mothers took them while pregnant.
Stronger warnings about use during pregnancy will be added to the drug labels, and valproates
pregnancy category for migraine use will be changed from "D" (the potential benefit of the drug in
pregnant women may be acceptable despite its potential risks) to "X" (the risk of use in pregnant
women clearly outweighs any possible benefit of the drug).
Valproate products will remain in pregnancy category D for treating epilepsy and manic episodes
associated with bipolar disorder.
BACKGROUND: Valproate products are approved for the treatment of certain types of epilepsy, the
treatment of manic episodes associated with bipolar disorder, and the prevention of migraine
headaches. They are also used off-label (for uses not approved by FDA) for other conditions,
particularly other psychiatric conditions.
This alert is based on the final results of the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD)
study showing that children exposed to valproate products while their mothers were pregnant had
decreased IQs at age 6 compared to children exposed to other anti-epileptic drugs. For additional
details, see the Drug Safety Communication Data Summary section.
RECOMMENDATION: Valproate products should not be used in pregnant women for prevention of
migraine headaches and should be used in pregnant women with epilepsy or bipolar disorder only if
other treatments have failed to provide adequate symptom control or are otherwise unacceptable.
Women who are pregnant and taking a valproate medication should not stop their medication but
should talk to their health care professionals immediately. Stopping valproate treatment suddenly can
cause serious and life-threatening medical problems to the woman or her baby.
Healthcare professionals and patients are encouraged to report adverse events or side effects related
to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting
Program:
Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the
address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
Read the complete MedWatch safety alert, including a link to the Drug Safety Communication at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350
868.htm.
Copies of this ICSI Health Care Guideline may be distributed by any organization to the organizations
employees but, except as provided below, may not be distributed outside of the organization without the
prior written consent of the Institute for Clinical Systems Improvement, Inc. If the organization is a legally
constituted medical group, the ICSI Health Care Guideline may be used by the medical group in any of
the following ways:
copies may be provided to anyone involved in the medical groups process for developing and
implementing clinical guidelines;
the ICSI Health Care Guideline may be adopted or adapted for use within the medical group only,
provided that ICSI receives appropriate attribution on all written or electronic documents and
copies may be provided to patients and the clinicians who manage their care, if the ICSI Health
Care Guideline is incorporated into the medical groups clinical guideline program.
All other copyright rights in this ICSI Health Care Guideline are reserved by the Institute for Clinical
Systems Improvement. The Institute for Clinical Systems Improvement assumes no liability for any adaptations or revisions or modifications made to this ICSI Health Care Guideline.
www.icsi.org
Copyright 2013 by Institute for Clinical Systems Improvement
Eleventh Edition
January 2013
Diagnosis algorithm
Evaluate type of headache
Take a detailed history
and assess functional
impairment
Rule out causes for
concern
Consider secondary
headache disorder
Refer to specialist when
indicated
Tension-Type Headache
algorithm
Establish diagnosis
Acute treatment
Prophylactic treatment
Patient education and
lifestyle modifications
Migraine Treatment
algorithm
Categorize and select
treatment based on
severity and functional
impairment
Consider special
treatment (including
DHE) for status
headache (See
Dihydroergotamine
Mesylate [DHE] algorithm)
Patient education and
lifestyle modifications
Cluster Headache
algorithm
Establish diagnosis
Acute treatment
Prophylactic treatment
Patient education and
lifestyle modifications
Is patient a female
whose headache may be
hormonally related?
no
yes
6
Menstrual-Associated
Migraine algorithm
Perimenopausal or
Menopausal
Migraine algorithm
On Estrogen-Containing
Contraceptives or
Considering EstrogenContaining Contraceptives
Migraine algorithm
Migraine Prophylactic
Treatment algorithm
Diagnosis Algorithm
10
11
12
Causes for concern:
Subacute and/or
progressive headache over
months
New or different headache
"Worst headache ever"
Any headache of maximum
severity at onset
Onset after the age of 50
years old
Symptoms of systemic
illness
Seizures
Any neurological signs
11
Detailed History
Characteristics of the
headache
Assess functional
impairment
Past medical history
Family history of migraines
Current medications and
previous medications for
headache (Rx and
over-the-counter)
Social history
Review of systems - to rule
out systemic illness
12
13
yes
Causes for
concern?
Consider secondary
headache disorder
no
21
Specialty
consultation
indicated?
14
Meets
criteria for primary
headache disorder?
no
24
yes
Refer to headache
specialist
no
25
22
Diagnosis of
primary headache
confirmed?
Perform diagnostic
testing if indicated
yes
yes
no
23
no
15
Findings
consistent with
secondary
headache?
26
yes
Determine secondary
headache type
Out of guideline
Evaluate type of
primary headache.
Initiate patient education
and lifestyle management
16
17
18
19
20
Migraine
(See Migraine
Treatment
algorithm)
Tension-type
(See Tension-Type
Headache
algorithm)
Cluster
(see Cluster
Headache
algorithm)
Chronic daily
headache
Other headache
Sinus Headache
15
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Institute for Clinical Systems Improvement
28
29
Is patient
experiencing a
typical headache?
Return to Diagnosis
algorithm
no
yes
30
31
35
38
43
Mild
Moderate
Severe
Status
(> 72 hour duration)
36
39
Moderate
treatment:**
- DHE
- Ergotamine
tartrate
- Lidocaine nasal
- Midrin and
others
- NSAIDs
- 5 HT agonists
(triptans)
See treatment
in #32
Severe
- Prochlorperazine
- Chlorpromazine
- DHE
- Ketorolac IM
- Magnesium
Sulfate IV
- 5 HT agonists
(triptans)
See treatment
in #32
- IV valproate
sodium
Adjunctive drug
therapy
Adjunctive drug
therapy
32
Mild treatment:**
- APAP/ASA/
Caffeine
- ASA
- Lidocaine nasal
- Midrin
- NSAIDs
- 5 HT agonists
(triptans)
Almotriptan
Eletriptan
Frovatriptan
Naratriptan
Rizatriptan
Sumatriptan
Sumatriptan/
Naproxen
Zolmitriptan
44
Adjunctive therapy
47
45
Patient meets
criteria for
DHE?
no
Chlorpromazine,
IV valproate sodium,
IV magnesium sulfate
or prochlorperazine
yes
46
Refer to DHE
algorithm
48
Successful?
Adjunctive drug
therapy
yes
no
37
33
Successful?
no
Successful?
no
yes
40
49
Successful?
Opiates
yes
yes
no
50
Successful?
yes
41
Specialty
consultation
indicated?
no
no
51
Dexamethasone
yes
52
42
Consultation with
headache specialist
Refer to:
Menstrual-Associated
Migraine algorithm
Perimenopausal or
Menopausal Migraine
algorithm
On Estrogen-Containing
Contraceptives or
Considering EstrogenContaining
Contraceptives with
Migraine algorithm
Successful?
yes
34
54
no
Headache resolved
53
yes
Is this a
hormone-related
migraine?
no
55
Is patient
candidate for
prophylactic
treatment?
56
no
Continue acute
treatment
yes
57
Refer to
Migraine Prophylactic
Treatment algorithm
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Tension-type
headache
59
60
Patient meets
criteria for tensiontype headache?
no
Return to Diagnosis
algorithm
yes
62
61
Does patient
currently have a
headache?
Acute treatment:
Acetaminophen
Aspirin
NSAIDs
Midrin
Adjunctive therapy
yes
no
63
64
Consider referral
Out of guideline
65
no
yes
Is patient candidate
for prophylactic
treatment?
Therapy
successful?
no
yes
66
Prophylactic treatment:
Amitriptyline
Other TCAs
Venlafaxine XR
Adjunctive therapy
68
67
Therapy
successful?
yes
no
69
Continue therapy
Return to Table of Contents
Institute for Clinical Systems Improvement
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Cluster headache
71
72
Patient meets
criteria for cluster
headache?
Return to Diagnosis
Algorithm
no
yes
74
73
Is patient currently
in a cluster cycle?
Reinforce patient
education
Consider pre-cluster
cycle specialty consult
no
yes
75
Acute treatment:
Oxygen
Sumatriptan SQ and
intranasal
Zolmatriptan intranasal
DHE
Start prophylactic
treatment
76
Bridging treatment
Corticosteroids
Occipital nerve block
77
Maintenance prophylaxis
Verapamil (first-line)
Avoid alcohol consumption
during cluster cycle
Therapy
successful?
no
yes
80
81
Continue therapy
through cycle, then
taper
yes
Therapy
successful?
82
no
Consider referral/
Out of guideline
www.icsi.org
84
Intravenous metoclopramide
10 mg IV
85
86
Return to Migraine
Treatment algorithm,
box 48
Caution: Dihydroergotamine mesylate must not be given to or continued in patients who develop the following
conditions:
Pregnancy
History of ischemic heart disease
History of Prinzmetal's angina
Severe peripheral vascular disease
Onset of chest pain following administration of test dose
Within 24 hours of receiving any triptan or ergot derivative
Elevated blood pressure
Patients with hemiplegic or basilar-type migraines*
Cerebrovascular disease
* Basilar-type migraine is defined as three of the following features: diplopia, dysarthria, tinnitus, vertigo, transient
hearing loss or mental confusion (Headache Classification Subcommittee of the International Headache Society, 2004
[Guideline]).
www.icsi.org
Menstrual only
Headache occurs exclusively
2 days before and first 2 days
of menstrual cycle
Associated but not limited to
menstruation
Occurs > 6-8 days/month
OR
Occurs > 3 days/month when
optimally treated and still
debilitating
88
89
90
yes
Therapy
successful?
Continue therapy
no
91
Consider cyclic
prophylaxis
NSAIDs
Triptans
94
92
93
Continue therapy
yes
no
Patient improves?
95
96
Continue therapy
yes
Patient improves?
no
97
Consider consult
with headache
specialist
Return to Table of Contents
Institute for Clinical Systems Improvement
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Perimenopausal or
menopausal with active
migraine history and is a
potential candidate for HT
99
100
Patient is
willing to start
HT?
no
yes
101
102
Continue therapy
1 03
Hormone therapy
Oral, transvaginal or transdermal
estrogen
Progestin if indicated
Estrogen-containing
contraceptives
Refer to the On Estrogen-Containing
Contraceptives or Considering
Estrogen-Containing Contraceptives
with Migraine algorithm
yes
Successful?
no
104
105
Successful?
no
yes
108
107
106
yes
Successful?
no
Specialty consultation
Return to Migraine
Treatment algorithm
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Institute for Clinical Systems Improvement
On estrogen-containing contraceptives
or considering estrogen-containing
contraceptives with migraine
110
Patient prefers
non-estrogen
birth control?
no
yes
111
112
Progestin methods
- Progestin-only contraceptives
- Depo-Provera
- IUD
Non-hormonal contraceptive methods
118
113
no
no
yes
At risk?
Headaches worsen?
Increase in frequency
Increase in severity
Develop an aura
yes
114
Continue therapy
115
no
120
119
Low-estrogen
contraceptives
Headaches worsen?
Increase in frequency
Increase in severity
Develop an aura
yes
116
117
Continue therapy
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Institute for Clinical Systems Improvement
121
122
Prophylactic treatment
Assess factors that may
trigger migraine
Treatment:
Medication
- Beta-blocker
- Tricyclic antidepressants
- Ca++ channel blockers
- Antiepileptic drugs
Divalproex
Topiramate
Gabapentin
Reinforce education and
lifestyle management
Consider other therapies
(biofeedback, relaxation)
Screen for depression and
generalized anxiety
124
12 3
Successful? *
yes
no
125
127
126
Successful? *
yes
yes
no
128
Try combination of
beta-blockers and
tricyclics
130
12 9
Successful? *
no
131
Third-line prophylaxis
treatment or consultation
with headache specialist
www.icsi.org
10
Table of Contents
Work Group Leader
John Beithon, MD
Family Medicine, Lakeview
Clinic
HealthPartners Medical
Group and Regions
Hospital
Pamela Kildahl, RPh
Pharmacy
Hutchinson Medical
Center
Julie Krenik, MD
Family Medicine
Mayo Clinic
Mary Gallenberg, MD
Gynecology
Mark Liebow, MD
Internal Medicine
Linda Linbo, RN
Nursing
Jerry Swanson, MD
Neurology
ICSI
Kari Johnson, RN
Clinical Systems
Improvement Facilitator
Cassie Myers
Clinical Systems
Improvement Facilitator
Algorithm (Main)..........................................................................................................................................1
Algorithm (Diagnosis)..................................................................................................................................2
Algorithm (Migraine Treatment)..................................................................................................................3
Algorithm (Tension-Type Headache)............................................................................................................4
Algorithm (Cluster Headache)......................................................................................................................5
Algorithm (Dihydroergotamine Mesylate [DHE])........................................................................................6
Algorithm (Menstrual-Associated Migraine)................................................................................................7
Algorithm (Perimenopausal or Menopausal Migraine)................................................................................8
Algorithm (On Estrogen-Containing Contraceptives or Considering
Estrogen-Containing Contraceptives with Migraine)..............................................................................9
Algorithm (Migraine Prophylactic Treatment)...........................................................................................10
Evidence Grading...................................................................................................................................12-13
Foreword
Introduction...........................................................................................................................................14
Scope and Target Population................................................................................................................15
Aims......................................................................................................................................................15
Clinical Highlights...........................................................................................................................15-16
Implementation Recommendation Highlights......................................................................................16
Related ICSI Scientific Documents......................................................................................................16
Definition..............................................................................................................................................16
Special Circumstances..........................................................................................................................17
Annotations............................................................................................................................................18-45
Annotations (Diagnosis)..................................................................................................................18-28
Annotations (Migraine Treatment)..................................................................................................28-34
Annotations (Tension-Type Headache)...........................................................................................34-35
Annotations (Cluster Headache)......................................................................................................35-37
Annotations (Dihydroergotamine Mesylate [DHE])............................................................................37
Annotations (Menstrual-Associated Migraine)...............................................................................38-40
Annotations (Perimenopausal or Menopausal Migraine)................................................................40-41
Annotations (On Estrogen-Containing Contraceptives or Considering
Estrogen-Containing Contraceptives with Migraine)..................................................................41-42
Annotations (Migraine Prophylactic Treatment).............................................................................42-45
Quality Improvement Support...............................................................................................................46-62
Aims and Measures................................................................................................................................47-48
Measurement Specifications............................................................................................................49-59
Implementation Recommendations.............................................................................................................60
Implementation Tools and Resources.........................................................................................................60
Implementation Tools and Resources Table...........................................................................................61-62
Supporting Evidence.................................................................................................................................63-83
Conclusion Grading Worksheet Summary..................................................................................................64
Conclusion Grading Worksheets............................................................................................................65-67
Conclusion Grading Worksheet A Annotation #91
(Non-Steroidal Anti-Inflammatory Drugs).................................................................................65-66
Conclusion Grading Worksheet B Annotation #111 (Risk of Stroke)...............................................67
References..............................................................................................................................................68-75
Appendices.............................................................................................................................................76-83
Appendix A Drug Treatment for Headache..................................................................................76-79
Appendix B Drug Treatment for Adjunctive Therapy.......................................................................80
Appendix C Headache Clinical Summary....................................................................................81-83
Disclosure of Potential Conflicts of Interest.......................................................................................84-86
Acknowledgements....................................................................................................................................87-88
Document History.......................................................................................................................................89
ICSI Document Development and Revision Process..................................................................................90
www.icsi.org
11
Evidence Grading
Literature Search
A consistent and defined process is used for literature search and review for the development and revision of ICSI guidelines. The literature search was divided into two stages to identify systematic reviews,
(stage I) and randomized controlled trials, meta-analysis and other literature (stage II). Literature search
terms used for this revision are below and include diagnosis of headache, migraine treatment, tension-type
headache treatment, cluster headache treatment, menstrual-associated migraine treatment, perimenopause
or menopause migraine treatment, pharmacologic treatment of headache, Botox and headache from June
2010 through July 2012
GRADE Methodology
Following a review of several evidence rating and recommendation writing systems, ICSI has made a decision
to transition to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
GRADE has advantages over other systems including the current system used by ICSI. Advantages include:
explicit and comprehensive criteria for downgrading and upgrading quality of evidence ratings;
clear separation between quality of evidence and strength of recommendations that includes a
transparent process of moving from evidence evaluation to recommendations;
clear, pragmatic interpretations of strong versus weak recommendations for clinicians, patients and
policy-makers;
All existing Class A (RCTs) studies have been considered as high quality evidence unless specified
differently by a work group member.
All existing Class B, C and D studies have been considered as low quality evidence unless specified
differently by a work group member.
All existing Class M and R studies are identified by study design versus assigning a quality of
evidence. Refer to Crosswalk between ICSI Evidence Grading System and GRADE.
All new literature considered by the work group for this revision has been assessed using GRADE
methodology.
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Institute for Clinical Systems Improvement
12
Evidence Grading
Crosswalk between ICSI Evidence Grading System and GRADE
High, if no limitation
Low
Class B: [observational]
Cohort study
Class C: [observational]
Non-randomized trial with concurrent or
historical controls
Case-control study
Population-based descriptive study
Study of sensitivity and specificity of a
diagnostic test
Low
Low
*Low
* Following individual study review, may be elevated to Moderate or High depending upon study design
Meta-analysis
Systematic Review
Decision Analysis
Cost-Effectiveness Analysis
Class D: [observational]
Cross-sectional study
Case series
Case report
Class M: Meta-analysis
Systematic review
Decision analysis
Cost-effectiveness analysis
Low
Low
Low
Guideline
Low
Low
Evidence Definitions:
High Quality Evidence = Further research is very unlikely to change our confidence in the estimate of effect.
Moderate Quality Evidence = Further research is likely to have an important impact on our confidence in the
estimate of effect and may change the estimate.
Low Quality Evidence = Further research is very likely to have an important impact on our confidence in the
estimate of effect and is likely to change the estimate or any estimate of effect is very uncertain.
In addition to evidence that is graded and used to formulate recommendations, additional pieces of
literature will be used to inform the reader of other topics of interest. This literature is not given an
evidence grade and is instead identified as a Reference throughout the document.
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Institute for Clinical Systems Improvement
13
Foreword
Introduction
This guideline discusses the headache disorders most commonly seen in primary care offices. It is not a
comprehensive discussion of diagnosis and treatment of all headache syndromes, since many headaches
are rare and felt best treated by headache specialists or neurologists with specialization in headache. It is
intended for primary care clinicians to help with their diagnosis and treatment of four main types of headache:
migraine, tension-type headache, cluster headache and chronic daily headache. This guideline is necessarily
long and may be considered by some to be cumbersome. However, extensive information pertaining to
headaches is covered, along with the typical medications. As there are multiple easy-to-access information
sources available containing current detailed drug information, drug tables in the appendices highlight only
selected drugs whose dosing, side effects and contraindications might otherwise be challenging to locate.
For most headaches, diagnosis is made on the basis of history and physical exam with no imaging or laboratory assistance. There are, however, causes for concern listed in the algorithms, which may direct clinicians
to specific testing or referral.
Headache is a very common problem presenting to primary care clinicians, with about 3% of emergency
department visits and 1.3% of outpatient visits for headaches. While tension-type headache is the most
common type of headache overall, migraine is the most common headache type seen in clinical practice,
with visits for tension-type headache and cluster headaches being much less common in clinician's offices.
Therefore migraine is the first and primary headache type reviewed.
Migraine is a genetically influenced chronic brain condition marked by paroxysmal attacks of moderate to
severe throbbing headache. About 324 million persons suffer from migraine worldwide according to the
World Health Organization. Nearly 18% of women and 8% of men in the United States suffer from migraine
in any given year. Typically the disorder begins in adolescence and young adults but the lifetime cumulative incidence is 43% for women and 18% for men. Over 25% of migraine sufferers have more than three
headache days per month (Loder, 2010 [Low Quality Evidence]).
Women headache sufferers may present with a hormonal component to the course of headaches over their
lifetime, and an algorithm for treatment of hormone-related headache is also included. Headaches over three
times a month are often treated with prophylactic treatment as overuse of medication for acute migraine
may actually cause chronic headache.
Because headache is such a common disorder that is often misdiagnosed and undertreated or mistreated,
improved diagnosis of headache syndromes will improve the patient's experience of care, notably quality of
and satisfaction with care. Morbidity due to headaches is substantial, so improved diagnosis and treatment
will improve the health of the population. Reducing office visits, emergency department visits, and inpatient
admissions for uncontrolled headache syndromes along with reducing unnecessary tests and procedures
for headache diagnosis is likely to reduce total costs of care even if there are more visits for diagnosis of
headache and increased costs for headache-specific drugs.
Return to Table of Contents
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Institute for Clinical Systems Improvement
14
Foreword
Patients age 12 years and older who present with headache. For the purpose of this guideline, pain that
primarily involves the back of the neck and only involves the head to a limited extent is not considered a
headache. This guideline does not specifically address occipital neuralgia.
Return to Table of Contents
Aims
1. Increase the accurate diagnosis of primary headaches in patients age 12 years and older. (Annotation
#11)
2. Increase the percentage of patients with primary headache diagnosis who receive educational materials
about headache. (Annotation #15)
3. Increase the percentage of patients with primary headache syndrome who receive prophylactic treatment.
(Annotations #66, 77, 91, 94, 122, 131)
4. Increase the percentage of patients with migraine headache who have improvement in their functional
status. (Annotation #15)
5. Increase the percentage of patients with migraine headache who have a treatment plan or report adherence to a treatment plan. (Annotations #32, 33, 36, 42, 43, 44)
6. Decrease the percentage of patients with migraine headache who are prescribed opiates and barbiturates
for the treatment of migraines to less than 5%. (Annotations #36, 49)
7. Increase the percentage of patients with migraine headache who have appropriate acute treatment.
(Annotations #30, 32, 36)
Return to Table of Contents
Clinical Highlights
Headache is diagnosed by history and physical examination with limited need for imaging or laboratory
tests. (Annotation #11; Aim #1)
Warning signs of possible disorder other than primary headache are (Annotation #12; Aim #1):
-
-
-
-
-
-
Evidence such as fever, hypertension, myalgias, weight loss or scalp tenderness suggesting a systemic
disorder
Presence of neurological signs that may suggest a secondary cause
Seizures
Migraine-associated symptoms are often misdiagnosed as "sinus headache" by patients and clinicians.
Most headaches characterized as "sinus headaches" are migraines. (Annotation #15; Aim #1).
Early treatment of migraines with effective medications improves a variety of outcomes including duration, severity and associated disability. (Annotations #32, 36; Aim #7)
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Return to Table of Contents
15
Foreword
Drug treatment of acute headache should generally not exceed more than two days per week on a regular
basis. More frequent treatment other than this may result in medication-overuse chronic daily headaches.
(Annotations #32, 36; Aim #7)
Inability to work or carry out usual activities during a headache is an important issue for migraineurs.
(Annotation #30; Aim #4)
Prophylactic therapy should be considered for all patients. (Annotations #66, 77, 91, 94, 122, 131; Aim
#3)
Migraines occurring in association with menses and not responsive to standard cyclic prophylaxis
may respond to hormonal prophylaxis with the use of estradiol patches, creams or estrogen-containing
contraceptives. (Annotation #94; Aim #3)
Women who have migraines with aura have a substantially higher risk of stroke with the use of estrogencontaining contraceptive compared to those without migraines. Headaches occurring during perimenopause or after menopause may respond to hormonal therapy. (Annotations #109, 111; Aim #5)
Most prophylactic medications should be started in a low dose and titrated to a therapeutic dose to minimize side effects and maintained at target dose for 8-12 weeks to obtain maximum efficacy. (Annotation
#122; Aims #3, 5, 7)
The following system changes were identified by the guideline work group as key strategies for health care
systems to incorporate in support of the implementation of this guideline.
Develop a system for assessment of headache based on history and functional impairment.
Develop a system for results of this assessment to be used for identification of treatment options/
recommendations.
Develop systems that allow for consistent documentation and montoring based on type of headache.
Develop a system for follow-up assessment that identifies success in management of headache in
the primary care setting.
Definition
Clinician All health care professionals whose practice is based on interaction with and/or treatment of a
patient.
Return to Table of Contents
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16
Foreword
Special Circumstances
Adolescents
At this time the majority of the adolescent literature supports a strong placebo effect in this age group.
Success of triptans and prophylactic medications in patients age 12-17 yield similar positive outcomes as in
adult studies, but placebo administered in blinded, controlled studies has a similar effect. There has been a
recent study that supports the use of almotriptan with statistically significant efficacy over placebo. As an
acute treatment, almotriptan in the dose of 12.5 mg was effective in relieving pain and associated symptoms
and was well tolerated (Linder, 2008 [High Quality Evidence]).
As a prophylactic treatment, topiramate 100 mg/day was effective in reduction of the number of migraine
headaches a month (Lewis, 2009 [High Quality Evidence]).
Psychological treatments, principally relaxation and cognitive behavioral therapies are effective treatments
of childhood headache (Eccleston, 2009 [Meta-analysis/Systematic Review]).
Pregnancy and Breastfeeding
Special consideration should be given to medication selection and management during pregnancy and
breastfeeding, considering the risks and benefits of selected drugs and their efficacy.
Return to Table of Contents
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17
Algorithm Annotations
Diagnosis Algorithm Annotations
10. Patient Presents with Complaint of a Headache
Recommendation:
Clinicians should perform an appropriate prompt evaluation of the patient who presents
with headache and initiate acute treatment.
Migraine is the most common headache disorder seen by primary care clinicians (Tepper, 2004 [Low Quality
Evidence]).
A patient may present for care of headaches during an attack or during a headache-free period. If a patient
presents during a headache, appropriate evaluation (history, examination, appropriate testing) needs to be
in a timely fashion. Once the diagnosis of primary headache is established, acute treatment is instituted.
If the patient has a history of recurrent headaches, a plan for treatment (acute and prophylactic) needs to
be established.
Return to Algorithm
Clinicians should gather a detailed history, including a focused physical and neurological
exam, of the patient who presents with headache.
Headache is one of the most frequent diseases seen in clinics by health care clinicians.
Clinicians, minimal general physical examination is performed at the first consultation of patient presenting
with a headache.
Symptoms and signs with the use of criteria can diagnose headache. The International Classification of
Headache Disorders, second edition (ICHD-II) system presently provides the gold standard. As empirical
evidence and clinical experience accumulate, criteria for diagnosing headaches will be revised (Olsen, 2006
[Reference]).
Detailed History
Inquire about functional disabilities at work, school, housework or leisure activities during the past three
months (informally or using well-validated disability questionnaire).
Assessment of the headache characteristics requires determination of the following:
Temporal profile:
Usual time of onset (season, month, menstrual cycle, week, hour of day)
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Autonomic features:
Nasal stuffiness
Rhinorrhea
Tearing
Ophthalmological examination to include pupillary symmetry and reactivity, optic fundi, visual
fields, and ocular motility
Cranial nerve examination to include corneal reflexes, facial sensation and facial symmetry
Symmetry of muscle tone, strength (may be as subtle as arm or leg drift), or deep tendon reflexes
Sensation
Plantar response(s)
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Headache features beyond that of International Classification of Headache Disorders, second edition (ICHDII) system criteria should raise concern of a more sinister underlying cause (Pryse-Phillips, 1997 [Guideline]).
Causes for concern in the diagnosis of headaches may alter a diagnosis of migraine to a secondary diagnosis
of headache, which can be more serious and/or life-threatening (Dalessio, 1994 [Guideline]; Edmeads,
1988 [Low Quality Evidence]).
Causes for concern must be evaluated irrespective of the patient's past history of headache. Warning signs
of possible disorder other than primary headache are:
A new or different headache or a statement by a headache patient that "this is the worst headache
ever."
Persistent headache precipitated by a Valsalva maneuver such as cough, sneeze, bending or with
exertion (physical or sexual).
Evidence such as fever, hypertension, myalgias, weight loss or scalp tenderness suggesting a systemic
disorder.
Neurological signs that may suggest a secondary cause. For example: meningismus, confusion,
altered levels of consciousness, changes or impairment of memory, papilledema, visual field defect,
cranial nerve asymmetry, extremity drifts or weaknesses, clear sensory deficits, reflex asymmetry,
extensor plantar response, or gait disturbances.
Seizures.
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The presence of the symptoms or signs listed above suggests a secondary cause for the headache and could
be indicative of an underlying organic condition. Alternate diagnoses include subarachnoid hemorrhage,
tumor, meningitis, encephalitis, temporal arteritis, idiopathic intracranial hypertension and cerebral venous
thrombosis, among others.
Secondary Headaches
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A new or different headache or a statement by a headache patient that "this is the worst headache
of my life":
Primary headache disorders (mainly tension-type headache and migraine) are exceedingly common. A
history of a primary headache disorder does not confer protection against a new, serious process that
presents with headache. The acuteness of a headache will largely define the differential diagnosis.
Headache that presents suddenly, "like a thunderclap," can be characteristic of several serious intracranial processes, including subarachnoid hemorrhage, venous sinus thrombosis, bacterial meningitis,
spontaneous cerebral spinal fluid leak, carotid dissection, and rarely, pituitary apoplexy and hypertensive
encephalopathy. The first investigation is a computed tomography head scan without contrast. If there
is no evidence of a subarachnoid hemorrhage, a lumbar puncture should be performed. If both studies
are normal and the suspicion of subarachnoid hemorrhage is still high, a magnetic resonance imaging
with and without gadolinium should be obtained. Neurological consultation is indicated and further
tests for consideration include magnetic resonance angiogram and magnetic resonance venogram.
If the headache is more subacute in onset, chronic meningitis may need to be considered along with
a space-occupying intracranial lesion or hydrocephalus. Again, neuroimaging should be performed.
Whether a lumbar puncture is done will be guided by the index of suspicion regarding a meningeal
process (e.g., meningitis).
Headache precipitated by a Valsalva maneuver such as cough, sneeze, bending or with exertion:
Valsalva headaches, while often representing primary cough headache, can signal an intracranial
abnormality, usually of the posterior fossa. The most commonly found lesion is a Chiari malformation,
although other posterior fossa lesions are sometimes found. Less commonly there are intracranial lesions
located elsewhere. A magnetic resonance imaging needs to be obtained to appropriately investigate for
these possibilities. Exertional headache, such as with exercise or during sexual activity, may represent
a benign process such as migraine. However, if the headache is severe or thunderclap in onset, investigations will be necessary as already outlined above.
Symptoms suggestive of a systemic disorder such as fever, myalgias, weight loss or scalp tenderness or a known systemic disorder such as cancer or immune deficiency:
Systemic disorders, while not incompatible with a coexistent primary headache disorder, should signal
caution. Patients should be carefully evaluated. Obviously, the differential diagnosis will be long, and
the index of suspicion for any given process will largely depend on the clinical setting.
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Presence of subtle neurological signs suggests a secondary cause for headache. For example,
meningismus, confusion, altered level of consciousness, memory impairment, papilledema, visual
field defect, cranial nerve abnormalities, pronator drift, extremity weakness, significant sensory
deficits, reflex asymmetry, extensor plantar response, or gait disturbance when accompanying a
headache should elicit caution:
While neurological signs may be unrelated to a headache, previously undocumented neurological
findings that are presumably new need to be carefully considered. Usually cranial imaging will be the
initial study. Depending on the index of suspicion, lumbar puncture and blood studies may be indicated.
Seizures:
While seizures can occasionally be a manifestation of a primary headache disorder such as migraine, this
is the exception and not the rule; it is a diagnosis of exclusion. Other etiologies for seizures including
space-occupying lesions, infection, stroke and metabolic derangements will need to be considered.
Again, magnetic resonance imaging is the imaging procedure of choice unless there is an issue of acute
head trauma, in which case a computed tomography head scan should be obtained initially.
subdural hematoma
epidural hematoma
acute hydrocephalus
tumor
obstructive hydrocephalus
This list is not intended to be all-inclusive but rather to represent the most commonly seen diagnosis for
secondary headache by the primary care clinician.
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The International Classification of Headache Disorders, second edition (ICHD-II) system for migraine
has been studied in a community population sample without consideration of treatment. Findings suggest
that the best criteria differentiating migraine from other headache types are the presence of nausea and/or
vomiting in combination with two of the following three symptoms: photophobia, phonophobia and osmophobia (Olesen, 2006 [Reference]).
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Cluster Headache
A. Severe unilateral orbital, supraorbital and/or temporal pain lasting 15 to 180 minutes untreated
B. Attack is associated with at least one of the following signs on the side of the pain:
1. Conjunctival injection
2. Lacrimation
3. Nasal congestion
4. Rhinorrhea
5. Forehead and facial swelling
6. Miosis
7. Ptosis
8. Eyelid edema
9. Agitation, unable to lie down
C. Frequency from one every other day to eight per day
D. Organic disorder is ruled out by the initial evaluation or by diagnostic studies. If another disorder is present, the
headaches should not have started in close temporal relationship to the disorder.
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Chronic Headaches
Chronic Tension-Type Headache
Chronic Migraine
A. Headache (tension type and/or migraine) on greater
A. Average frequency of greater than 15 attacks per
than or equal to 15 days per month for at least three
month
months*
B. At least two of the following pain characteristics:
B. Occurring in a patient who has had at least five
1. Pressing/tightening quality
attacks fulfilling criteria for 1.1 Migraine without
2. Mild to moderate intensity (may inhibit, but
aura
does not prohibit activities)
C. On greater than or equal to eight days per month for
3. Bilateral location
at least three months headache has fulfilled C1
4. Not aggravated by routine physical activity
and/or C2 below, that is, has fulfilled criteria for
C.
Both of the following:
pain and associated symptoms of migraine without
1. No vomiting
aura
2. No more than one of the following: nausea,
1. Has at least two of a-d
photophobia or phonophobia
(a) unilateral location
D. Organic disorder is ruled out by the initial
(b) pulsating quality
evaluation or by diagnostic studies. If another
(c) moderate or severe pain intensity
disorder is present, the headaches should not have
(d) aggravation by or causing avoidance of
started in close temporal relationship to the
routine physical activity (e.g., walking or
disorder.
climbing stairs)
and at least one of a or b
(a) nausea and/or vomiting
(b) photophobia and phonophobia
2. Treated and relieved by triptan(s) or ergot
before the expected development of C1 above
D. No medication overuse and not attributed to another
causative disorder
*Characterization of frequently recurring headache generally
requires a headache diary to record information on pain and
associated symptoms day by day for at least one month.
Sample diaries are available at
http://www.headache.org/for_Professionals/Headache_Dairy.
Hemicrania Continua
Medication Overuse Headache
A. Headache for more than three months fulfilling
A. Headache greater than or equal to 15
criteria B-D
days/month
B. Regular overuse for greater than three months
B. All of the following characteristics:
of one or more acute/symptomatic treatment
unilateral pain without side-shift
drugs as defined under one or more treatment
daily and continuous, without pain-free
drugs as noted below:
periods
1.
Ergotamine, triptans, opioids or
The table "Modified Diagnostic Criteria" has been modified from the International Classification of Headache
Disorders, second edition (ICHD-II) system criteria and describes the differentiating criteria applicable for
the diagnosis of migraine and other primary headache disorders.
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Clinicians should provide patient education and lifestyle management options to patients
with headache.
Clinicians should instruct patients with headache to maintain a diary to clarify the
frequency, severity, triggers and treatment responses to their headaches.
Migraine-associated symptoms are often misdiagnosed as "sinus headache" by patients and clinicians. This
has led to the under diagnosis and treatment of migraine.
While education is of paramount importance in managing any condition, it is especially important in the
ongoing management of headache. Patients may have to make lifestyle changes, are often required to make
self-management choices in the treatment of individual headaches, and should maintain a diary to clarify the
frequency, severity, triggers and treatment responses. Most patients should be educated on the following:
Most patients will benefit from stress reduction, regular eating and sleeping schedules, and regular
aerobic exercise.
Chronic daily headache, including transformed migraine, is associated with overuse of analgesics
or acute treatment drugs. Use of NSAIDs for acute treatment of headache for more than nine days
per month or use of aspirin more than 15 days is associated with an increased risk of chronic daily
headaches.
Keeping a headache diary has the potential benefit of monitoring treatment effect upon severity,
frequency and disability.
Acute treatment has the goal of shortening individual headaches, while prophylaxis can reduce
frequency and possibly severity.
The presentation of four clinical characteristics and duration can help clinicians determine if the migraine
headache is likely, possible or unlikely by using the simple mnemonic POUNDing (Pulsatile quality; duration of 4 to 72 hours; Unilateral location; Nausea or vomiting; Disabling intensity) for the screening of
migraine headache (Detsky, 2006 [Decision Analysis]). See the table, "Modified Diagnostic Criteria" for
more information.
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Chronic daily headache refers to the presence of a headache more than 15 days per month for greater than
three months. Chronic daily headache is not a diagnosis but a category that may be due to disorders representing primary and secondary headaches. Secondary headaches are typically excluded with appropriate
neuroimaging and other tests. Chronic daily headache can be divided into those headaches that occur
nearly daily that last four hours or less and those that last more than four hours, which is more common.
The shorter-duration daily headache contains less-common disorders such as chronic cluster headache and
other trigeminal autonomic cephalgias. Only daily headaches of long duration are considered here.
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Chronic daily headache has been estimated to occur in 2.5-4% of the general population with surveys showing
that chronic tension-type headache is a bit more common than chronic migraine (transformed migraine).
In the clinic setting, chronic migraine is much more common than chronic tension-type headache. As with
migraine, chronic daily headaches are more common in women than men. An associated factor for chronic
daily headache is medication overuse. As outlined below, the Headache Classification Committee of the
International Classification of Headache Disorders, second edition (ICHD-II) has provided revised guidelines
for chronic migraine and medication overuse headache (Olesen, 2006 [Low Quality Evidence]).
In diary studies, patients who fulfill criteria for a diagnosis of the older definition of transformed migraine
also fulfill criteria for a diagnosis of the revised definition of chronic migraine, which is presented below
(Liebenstein, 2007 [Low Quality Evidence]; Bigal, 2006 [Low Quality Evidence]).
Please see the Modified Diagnostic Criteria table for the revised International Classification of Headache
Disorders, second edition (ICHD II) criteria for chronic migraine.
Medication-overuse headache
When medication overuse is present, this is the most likely cause of chronic headache. However, if the
acute headache relieving medications are discontinued for an extended period (often two months) and the
headache symptoms persist, it is likely chronic headache, not medication overuse type headache, even though
the ICHD-II criteria do not require this for the diagnosis of medication overuse.
Please see the Modified Diagnostic Criteria table for the International Classification of Headache Disorders,
second edition (ICHD-II), system revised criteria for medication-overuse headache.
Hemicrania Continua
A less common but not rare (and under recognized) cause for chronic daily headache is hemicrania continua.
Hemicrania continua description is a persistent, strictly unilateral headache responsive to indomethacin.
Please see the Modified Diagnostic Criteria table for the International Classification of Headache Disorders,
second edition (ICHD-II) criteria for hemicrania continua.
A much rarer disorder is that known as new daily persistent headache. This disorder is characterized by
its sudden onset, with the patient often able to note the date and time it began. There is no history of prior
significant headaches. It is typically bilateral and usually resembles migraine or tension-type headache.
Some individuals report an antecedent viral infection.
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Clinicians may consider specialty consultation when the diagnosis or etiology cannot
be confirmed, warning signals exist or quality of life is impaired.
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The decision to seek a specialty consultation will depend upon the practitioner's familiarity and comfort
with headache and its management. Specialty consultation may be considered when:
Headache attacks are occurring with a frequency or duration sufficient to impair the patient's quality
of life despite treatment or the patient has failed to respond to the acute remedies, or is in status
migrainosus
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Clinicians should use a detailed headache history, that includes duration of attacks and
the exclusion of secondary causes, as the principal means to diagnose primary headache.
Additional testing in patients without atypical symptoms or an abnormal neurologic
examination is unlikely to be helpful.
There are, as yet, no tests that confirm the diagnosis of primary headache. The diagnosis of primary headache
is dependent on the clinician. The work group recommends careful consideration before proceeding with
neuroimaging (computed tomography or magnetic resonance imaging). It is uncommon for neuroimaging
to detect an abnormality in persistent headaches of longer duration versus new onset situations. Selective
testing including neuroimaging or electroencephalogram, lumbar puncture, cerebrospinal fluid and blood
studies may be indicated to evaluate for secondary headache if causes of concern have been identified in the
patient history or physical examination. (See Annotation #12, "Causes for Concern?") Diagnosis may be
complicated if several headache types coexist in the same patient. The following symptoms significantly
increased the odds of finding a significant abnormality on neuroimaging in patients with non-acute headache:
History of headache causing awakening from sleep (although this can occur with migraine and
cluster headache) (Silberstein, 2000a [Guideline]).
In a study of 750 patients questioned, 47% had throbbing quality of headaches, while another study showed
30% of 1,000 cases of tension headache patients had pulsatile quality pain, 40% of all patients with migraine
have bilateral headaches. Duration of an attack is important. It is felt that pitfalls in interpreting diagnostic
criteria may lie in how questions are asked (Blau, 1993 [Low Quality Evidence]).
There is difficulty in developing an operational system to diagnose headaches with the lack of objective
diagnostic tests that identify various types of headache disorders absolutely. International Classification of
Headache Disorders, second edition (ICHD-II) criteria depend largely on a detailed headache history and
the exclusion of secondary cause for headache through a physical and neurological examination. Concern
of a secondary cause for headache may necessitate testing or further evaluation (Olesen, 1994 [Guideline]).
A total of 897 computed tomography scans or magnetic resonance images were done on migraine patients
with findings of three tumors and two arteriovenous malformations. At this time, there is evidence to define
the role of computed tomography and magnetic resonance imaging in the evaluation of headache patients.
1,800 computerized tomographic scans and magnetic resonance studies done on patients with headaches,
including those that were acute, progressively worsening, and chronic, found only 2.4% of those imaged
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had arteriovenous malformation, aneurysms, subdural hematoma or hydrocephalus was found (American
Academy of Neurology Quality Standards Subcommittee, 1994 [Guideline]).
In a retrospective study, 592 patients with headaches and normal neurological exam were examined by
computed tomography scanning between 1990 and 1993 at a cost of $1,000 per scan. None of the patients
had any serious intracranial pathology identified. This technique is costly and unrewarding (Akpek, 1995
[Cost-analysis]).
In a case series study 52 migraineurs were evaluated by spinal taps, cerebral spinal fluid analysis and tap
pressure. Pressures of cerebral spinal fluid and the chemistry evaluation of the same bore no direct relationship to the presence of headache diagnosis (Kovcs, 1989 [Low Quality Evidence]).
A summary statement reviewed articles from 1941 to 1994 with no study of electroencephalograms improving
diagnostic accuracy for the headache sufferer. Electroencephalography does not delineate subtypes or
screen for structural causes of headache effectively (American Academy of Neurology Quality Standards
Subcommittee, 1994 [Guideline]). In the absence of studies showing improved diagnostics with electroencephalogram, there is no indication for routine use of electroencephalograms in the diagnosis of headache.
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If diagnostic evaluation leads to a diagnosis other than primary headache, subsequent care of the patient
would fall beyond the scope of this guideline.
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Migraine is the most common headache disorder seen by primary care clinicians.
It is expected that a patient with headache will undergo a diagnostic workup (see the Diagnosis Algorithm)
establishing the diagnosis of migraine before initiating acute treatment.
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Each individual headache must be evaluated in the context of the patient's prior migraine headaches. The
practitioner must always remain alert to the possibility of secondary causes for headache, particularly when
there is a previously established history of a primary headache disorder such as migraine.
Migraine headache does not preclude the presence of underlying pathology (arterial dissection, intracranial
aneurysm, venous sinus thrombosis, ischemic or hemorrhagic stroke, temporal arteritis, etc.) that may also
present with "vascular headaches." If the history is scrutinized, ominous causes for headaches can often be
identified and treated with the potential to avoid catastrophe.
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Accurate categorization and characterization by both clinicians and patients is important. The categorization
of migraine influences choice of treatment method.
Severity levels:
Mild
Patient is aware of a headache but is able to continue daily routine with minimal alteration.
Moderate
Severe
Status
There may be additional features that influence choice of treatment. For example, parenteral administration
(subcutaneous, nasal) should strongly be considered for people whose time to peak disability is less than
one hour, who awaken with headache, and for those with severe nausea and vomiting.
Determining functional limitations during migraine episodes is the key to determining the severity and
therefore the best treatment for a patient. Clinicians and patients should stratify treatment based on severity
rather than using stepped care, though patients will often use stepped care within an attack. This algorithm
uses a stratified-care model.
Noise
Weather changes
Motion
Flying/high altitude
Physical strain
Lifestyle Habits:
Chronic high levels of stress
Smoking
Hormonal:
Puberty
Menopause
Menstruation or ovulation
Pregnancy
Depression
Excitement or exhilaration
"Let-down" response
Medications:
Nitroglycerin
Nifedipine
Oral contraceptives
Hormone therapy
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Dietary:
Dietary triggers vary considerably from patient to patient, are overall a minor and infrequent trigger for
migraine headaches, and will not consistently precipitate a migraine headache in an individual for whom
they have been a trigger in the past.
Citrus fruit
Aspartame
Caffeine
Aged cheese
Chocolate
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The guideline work group presumes most mild migraine headaches will be managed by self-care, which
implies an emphasis on over-the-counter medications. However, since only 2-12% of initially mild migraine
episodes remain mild (with the remainder progressing), treatments effective for mild headaches may be
useful for only a short time. Studies on treatment of migraine headache at the mild level show that triptans
are more effective in abolishing pain at this stage than if the headache is more severe. It is acceptable to
use other symptomatic headache relief drugs, as well as triptans, for mild headache. However, current
retrospective analyses of mild pain treatment studies reveal triptan response to two-hour pain freedom to
be superior to any other comparator drug. Please see Appendix A, "Drug Treatment for Headache," and
Appendix B, "Drug Treatment for Adjunctive Therapy."
Use of NSAIDs for acute treatment of headache for more than nine days per month or use of aspirin for
more than 15 days is associated with an increased risk of chronic daily headache.
Early treatment of migraines with effective medications improves a variety of outcomes including duration,
severity and associated disability (Valade, 2009 [Meta-analysis]).
Given a longer half-life of naratriptan, headache response is delayed with naratriptan when compared with
other selective 5-hydroxy tryptamine (5-HT) receptor agonists. However, headache recurrence may be less
frequent.
Second doses of triptans have not been shown to relieve headache more if the first dose has been ineffective.
Studies show that sumatriptan and naproxen sodium in combination may be more effective than either drug
alone. However, there are no studies that demonstrate that sumatriptan 85 mg/naproxen sodium 500 mg
is more effective than sumatriptan and naproxen sodium taken together. Therefore, a dose of sumatriptan
100 mg and a dose of naproxen sodium 550 mg taken at the same time is recommended.
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33. Successful?
Success for treatment of migraine is defined as complete pain relief and return to normal function within
two hours of taking medication. In addition, patients should not have intolerable side effects and should
find their medications reliable enough to plan daily activities despite migraine headache (Dowson, 2004a
[Low Quality Evidence]; Dowson, 2004b [Low Quality Evidence]).
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Consider reasons for treatment failure and change treatment plan.
Common reasons for migraine treatment failure:
Inadequate medication for degree of disability. Medication not well matched with most disabling
symptoms (e.g., using oral agents for a patient with vomiting) or inappropriate route of administration (e.g., using oral agents for a headache where maximum disability occurs quickly)
Inaccurate diagnosis
Patient adherence to therapy contributes to reaching treatment goals. The clinician-patient relationship plays
a key role in improving adherence. Clinicians should ask patients open-ended, non-threatening questions
regularly to assess adherence. Questions that probe for factors that contribute to non-adherence could include
those surrounding adverse reactions, misunderstandings of treatment, depression, cognitive impairment,
complex regimens and financial constraints.
Interventions to improve adherence include simplification of the drug regimen (frequency and complexity);
use of reminder systems; involvement of family or friends; a health care team approach including nurses,
pharmacists, and educators in addition to clinicians; written instructions; and educating the patient about
potential adverse effects, importance of therapy, and realistic treatment goals.
For example:
A. Assess the patient's knowledge of the condition and expectations for treatment:
"What is/will be the most difficult task for you in reaching your treatment goal?"
"How do you remember to take your medication each day? Do you use a reminder device such as
a pill box or alarm?"
"Do you have a difficult time opening medication bottles, swallowing pills or reading small print
on labels?"
"Are you comfortable with your ability to follow the treatment plan that we have designed
together?"
"Are you experiencing any unusual symptoms that you think may be due to your medication?"
Clinicians should avoid the use of opiates and barbiturates in the treatment of headache.
Early treatment of migraines with effective medications improves a variety of outcomes including duration,
severity, and associated disability (Valade, 2009 [Meta-analysis]).
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The use of opiates and barbiturates should be avoided. This guideline emphasizes the use of other agents
over opiates and barbiturates, recognizing that many migraineurs are currently treated with drugs from the
latter two classes. In general, opiates are characterized by having a short pain-relief window, release inflammatory neurochemicals, and increase vasodilation; none of these addresses the currently known treatment
issues and pathophysiology of migraine.
Meperidine should be avoided. The metabolite of meperidine, normeperidine, has a long half-life and
produces less analgesic effect, and there is an increased risk of seizures that cannot be reversed by naloxone.
We have specifically excluded butorphanol because of its high potential for abuse and adverse side-effect
profile.
If an opiate must be used, meperidine should not be the opiate selected.
See Appendix A, "Drug Treatment for Headache."
37. Successful?
A headache specialist is a practitioner, often but not always, a neurologist who has extensive experience,
knowledge of, and demonstrated high standards of health care in the field of headache. There are advanced
training programs in headache medicine.
The American Headache Society has a membership directory of practitioners interested in the field of headache and can be contacted if the name of a recommended specialist in a particular geographic location is
required. (American Headache Society can be reached by e-mail at AHSHQ@talley.com. The Web site:
http://www.americanheadachesociety.org)
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Algorithm Annotations
daily headache is to be discouraged. The prokinetic agent metoclopramide could be considered next. This
guideline has no other preferences.
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Dihydroergotamine mesylate is effective in halting intractable migraine attacks or migraine status. Dihydroergotamine mesylate is also effective in halting the acute cycle of cluster headaches.
Dihydroergotamine mesylate must not be given to patients with the following conditions:
Cerebrovascular disease
* Basilar-type migraine is defined as three of the following features: diplopia, dysarthria, tinnitus, vertigo, transient hearing loss or mental confusion (Headache Classification Subcommittee of the International Headache
Society, 2004 [Guideline]).
Intravenous dihydroergotamine mesylate is the method most frequently employed to terminate a truly
intractable migraine attack or migraine status. The protocol outlined in the dihydroergotamine mesylate
algorithm is effective in eliminating an intractable migraine headache in up to 90% of patients within 48
hours. This method of administration has also been found to be effective in terminating an acute cycle of
cluster headaches, as well as chronic daily headaches with or without analgesic/ergotamine rebound.
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Clinicians should treat patients with migraine > 72 hours who do not meet criteria for
DHE, with chlorpromazine, intravenous valproate sodium, intravenous magnesium
sulfate or prochlorperazine.
See Appendix A, "Drug Treatment for Headache," and Appendix B, "Drug Treatment for Adjunctive Therapy."
If chlorpromazine, valproate sodium or intravenous magnesium sulfate was used previously, one may not
wish to repeat.
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48. Successful?
49. Opiates
These are not drugs of first choice, and headache practice recommends against the use of meperidine. Normeperidine, the active metabolite of meperidine, has a long half-life and is neuroexcitatory and neurotoxic.
There is inconsistent absorption of opiates, at least with meperidine, when injected intramuscularly, and they
are less effective than when given intravenously. Opiates release inflammatory neurochemicals and increase
vasodilation that are mechanistically counterproductive to currently known migraine pathophsiology and
can exacerbate headaches. Studies have been done using meperidine, but the effects are likely due to class
effect, and other opiates are likely to be just as effective (Duarte, 1992 [High Quality Evidence]). However,
it should be noted that there are no studies to support opiate effectiveness.
See Appendix A, "Drug Treatment for Headache," and Appendix B, "Drug Treatment for Adjunctive Therapy."
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51. Dexamethasone
See Appendix A, "Drug Treatment for Headache," and Appendix B,"Drug Treatment for Adjunctive Therapy."
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At this time the majority of the adolescent literature supports a strong placebo effect in this age group.
Success of triptans and prophylactic medications in patients age 12-17 yield similar positive outcomes as in
adult studies, but placebo administered in blinded, controlled studies has a similar effect. There has been a
recent study that supports the use of almotriptan with statistically significant efficacy over placebo. As an
acute treatment, almotriptan in the dose of 12.5 mg was effective in relieving pain and associated symptoms
and was well tolerated (Linder, 2008 [High Quality Evidence]).
Tension-type headache is one of the most common primary headaches. See Annotation #14, "Meets Criteria
for Primary Headache Disorder?" for episodic (less than 15 days per month) and chronic tension-type headache (more than 15 days per month).
It is important to evaluate the patient who comes to the office for tension-type headache for the possibility
of migraine. While the International Classification of Headache Disorders, second edition (ICHD-II) system
suggests migraine and tension-type headaches are distinct disorders, there is evidence to suggest that for the
migraineur, tension-type headache is actually a low-intensity migraine.
(Torelli, 2004 [High Quality Evidence]; Ashina, 2003 [Low Quality Evidence]; Zhao, 2003 [Low Quality
Evidence])
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Clinicians may utilize over-the-counter analgesics or prescription NSAIDs for tensiontype headache treatment.
Analgesics offer a simple and immediate relief for tension-type headache. Medication overuse is potentially
a concern that can lead to chronic daily headache. Use of drugs for acute treatment of headache for more
than nine days per month is associated with an increased risk of chronic daily headache.
See Appendix A, "Drug Treatment for Headache," and Appendix B, "Drug Treatment for Adjunctive Therapy."
(Torelli, 2004 [High Quality Evidence]; Ashina, 2003 [Low Quality Evidence]; Zhao, 2003 [Low Quality
Evidence])
Electromyography biofeedback has been found to have an effect on tension-type headaches. The goal is to
help patients recognize muscle tension. Fifty-three studies have shown medium to large effect (Bendtsen,
2010 [Guideline]).
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Prophylactic treatment, including the use of tricyclic antidepressants, may be used for
chronic tension-type headaches.
Prophylactic therapy is reserved for patients with chronic tension-type headache (more than 15 headaches
per month).
Tricyclic antidepressants are effective in reducing the frequency and severity of tension-type headache.
(Torelli, 2004 [High Quality Evidence]; Ashina, 2003 [Low Quality Evidence]; Zhao, 2003 [Low Quality
Evidence])
Return to Algorithm
There is no more severe pain than that sustained by a cluster headache sufferer. This headache is often termed
"suicide headache." Cluster headache is characterized by repeated short-lasting but excruciating intense
attacks of strictly unilateral peri-orbital pain associated with local autonomic symptoms or signs. The most
striking feature of cluster headache is the unmistakable circadian and circannual periodicity. Many patients
typically suffer daily (or nightly) from one or more attacks over a period of weeks or months.
(Dodick, 2000 [Low Quality Evidence]; Goadsby, 1997 [Low Quality Evidence]; Lipton, 1998 [High Quality
Evidence])
Return to Algorithm
Clinicians should utilize inhaled oxygen for the treatment of cluster headaches at a rate
of 7-15 L/min.
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Algorithm Annotations
Oxygen inhalation is highly effective when delivered at the beginning of an attack with a non-rebreathing
facial mask (7-15 L/min). Most patients will obtain relief within 15 minutes. Acute drugs may be difficult
to obtain in adequate quantity.
Subcutaneous sumatriptan and intranasal zolmitriptan are the most effective self-administered medication
for the relief of cluster headaches. Sumatriptan is not effective when used before the actual attack nor is
it useful as a prophylactic medication (Law, 2010 [Systematic Review]. Intranasal sumatriptan can also be
considered for acute treatment (Francis, 2010 [Moderate Quality Evidence]).
Dihydroergotamine mesylate provides prompt and effective relief from cluster headaches in 15 minutes, but
due to the rapid peak intensity and short duration of cluster headaches, dihydroergotamine mesylate may be
a less feasible option than sumatriptan.
See Appendix A, "Drug Treatment for Headache," and Appendix B, "Drug Treatment for Adjunctive Therapy."
(Dodick, 2000 [Low Quality Evidence]; Goadsby, 1997 [Low Quality Evidence]; Lipton, 1998 [High Quality
Evidence])
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Bridging treatment allows for the rapid suppression of cluster attacks in the interim until the maintenance
treatment reaches therapeutic levels.
Options for bridging treatment are:
Corticosteroids
(Capobianco, 2006 [Guideline]; Husid, 2006 [Low Quality Evidence]; Sandrini, 2006 [Low Quality
Evidence]; Ambrosini, 2005 [High Quality Evidence]; Peres, 2002 [Low Quality Evidence]; Dodick, 2000
[Low Quality Evidence])
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Algorithm Annotations
See Appendix A, "Drug Treatment for Headache," and Appendix B, "Drug Treatment for Adjunctive Therapy."
(Dodick, 2000 [Low Quality Evidence]; Olesen, 1999 [Reference]; Goadsby, 1997 [Low Quality Evidence];
Lipton, 1998 [High Quality Evidence])
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Metoclopramide (10 mg) is given either by direct intavenous injection over two-three minutes, or infused
intravenously in 50 mL of normal saline over 15 minutes. Each dose of metoclopramide should be administered 15 minutes prior to each dihydroergotamine mesylate injection. Although uncommon, acute extrapyramidal side effects such as dystonia, akathisia, and oculogyric crisis may occur after administration of
metoclopramide. Benztropine mesylate is effective in terminating this unusual adverse event, given as a 1
mg injection (intravenous or intramuscular). Often after five doses of metoclopramide, it may be given as
needed every eight hours for nausea (Ellis, 1993 [High Quality Evidence]).
Return to Algorithm
Begin dihydroergotamine mesylate 2 mg in 1,000 mL normal saline at 42 mL/hr. Limit the dose of DHE
to no more than 2 mg/24 hours.
Continue intravenous metoclopramide 10 mg IV every eight hours as needed for nausea.
Side effects:
If significant nausea occurs at any time, reduce the rate of dihydroergotamine mesylate to 21 to 30
mL/hr.
If diarrhea occurs, give diphenoxylate with atropine, one or two tablets, three times daily as
needed.
If excessive anxiety, jitteriness (akathisia) or dystonic reaction occurs, give intravenous benztropine
1 mg.
It may be continued up to seven days. Opioid analgesics should not be used since these are likely to prolong
the headache via analgesic rebound.
This is an adjusted Ford modification of the Raskin protocol. This is a continuous protocol as this is the
preferred method. This approach is an alternative to the intermittent dosing of dihydroergotamine mesylate
as outlined in the Raskin protocol, and some practitioners may prefer it rather than the intermittent dihydroergotamine mesylate protocol. Continuous dihydroergotamine mesylate, like the intermittent administration,
can be continued for seven days, although 72 hours is more typical. Opioid analgesics should not be used
with either protocol since these are likely to prolong the headache via analgesic rebound.
Ford, et al. described results of an open trial comparison between intermittent intravenous dihydroergotamine mesylate and continuous infusion dihydroergotamine mesylate. Success in treating migraine status
was virtually the same with each protocol. The Ford variation may be preferred by some clinicians. This
protocol should be used only with an intravenous pump (Ford, 1997 [Low Quality Evidence]; Queiroz, 1996
[Low Quality Evidence]; Raskin, 1986 [ Low Quality Evidence]).
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Algorithm Annotations
Clinicians should advise women who meet criteria for menstrual-associated migraine to
keep a continuous daily record of headache occurrence, severity, duration and menstrual
flow for at least two months.
"Menstrual migraine," a term misused by both patients and clinicians, lacks precise definition. The
International Classification of Headache Disorder, second edition (ICHS-II) system has proposed that
menstrual-only migraine be defined as attacks exclusively starting two days before and first two days
of the menstrual cycle (Pringsheim, 2008 [Meta-analysis]; Headache Classification Subcommittee of
the International Headache Society, 2004 [Guideline]). The woman should be free from attacks at all
other times of the cycle.
Many women who do not have attacks exclusively with menses are considered to have menstrualassociated migraines (MacGregor, 1996 [Low Quality Evidence]).
The clinician and patient need to discuss diary documentation. The patient should keep a continuous
daily record for at least two months to include the following:
Day/time of headache
Duration
Severity of headache
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Clinicians may consider non-hormonal cyclic prophylactic treatment with NSAIDs and
triptans for patients with menstrual-associated migraine.
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Algorithm Annotations
Triptans
There are good placebo studies supporting the use of triptans (sumatriptan, naratriptan, frovatriptan
and zolmitriptan) for cyclic prophylaxis (Tuchman, 2008 [High Quality Evidence]; Silberstein,
2000b [High Quality Evidence]; Newman, 1998 [Low Quality Evidence]).
Return to Algorithm
Clinicians may consider hormone prophylaxis treatment for patients with menstrualassociated migraines.
Transdermal estradiol
Estrogen levels decrease during the late luteal phase of the menstrual cycle, likely triggering migraine.
Estrogen replacement prior to menstruation has been used to prevent migraine.
Estradiol patches, 50-100 mcg, are applied 48 hours prior to expected onset of migraine and used for
one week.
The 50 mcg estradiol patch, applied 48 hours before anticipated onset of menses and continuing for
seven days, was effective in relieving headaches in a subgroup of women with menstrual migraines
confirmed by neurophysiological testing. Others have shown a better clinical outcome with 100 mcg
estradiol patches than with lower dose patches. Oral estrogen has been less effective than transdermal
estrogen in prophylaxis of menstrual migraine.
(Becker, 1999 [Low Quality Evidence]; Cupini, 1995 [Low Quality Evidence]; Larsson-Cohn, 1970
[Low Quality Evidence])
Estrogen-containing contraceptives
Estrogen-containing contraceptives have a variable effect on migraines, causing worsening of headaches
in some patients, improvement of headaches in a small percentage of patients, and no change in migraines
in other patients. We are not aware of any population-based studies on this topic.
The effect of estrogen-containing contraceptives on migraines is unpredictable. In one study, migraines
worsened in 39% of patients, improved in 3%, and remained unchanged in 39%. Another author reported
improvement in migraines in 35% of patients when estrogen-containing contraceptives were started.
(Becker, 1999 [Low Quality Evidence]; Cupini, 1995 [Low Quality Evidence]; Larsson-Cohn, 1970
[Low Quality Evidence])
In a contraceptive containing drospirenone, an extended 168-day placebo-free oral contraceptive regimen
showed a significant decrease in duration, severity of headaches and loss of function due to headache
compared with a standard 21/7 oral contraceptive cycle (Sulak, 2007 [Low Quality Evidence]). In 2011,
the Food and Drug Administration concluded that drospirenone may be associated with a higher risk for
blood clots than other progestin-containing pills. http://www.fda.gov/Drugs/DrugSafety/ucm273021.htm.
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Algorithm Annotations
functioning and quality of life and a decrease in analgesic medications used for headache relief. Two
patients discontinued therapy and had increased headache frequency. The monthly cost of GnRH agonist
therapy is about 10 times the cost of conventional hormone therapy. GnRH agonists and "add back"
therapy may also be associated with erratic bleeding. This therapy should probably be managed by a
gynecologist or endocrinologist in concert with a headache specialist.
Tamoxifen, danazol and bromocriptine have shown limited efficacy in treatment of menstrual migraine.
Whether oophorectomy is an effective treatment for refractory migraines is not settled at this time.
(Herzog, 1997 [Low Quality Evidence]; Murray, 1997 [Low Quality Evidence]; Lichten, 1991 [Low
Quality Evidence]; O'Dea, 1990 [Low Quality Evidence])
Return to Algorithm
Perimenopause is the span of time from the reproductive to the post-reproductive interval.
Hormone therapy may worsen, improve or leave migraines unchanged.
In a study of 112 women taking hormone therapy, 52 reported worsening of migraines, 50 reported improvement, and 10 reported no change in migraine headaches. More women improved with transdermal than
oral estrogen (Wang, 2003 [Low Quality Evidence]; Nappi, 2001 [High Quality Evidence]; MacGregor,
1997 [Low Quality Evidence]).
Women with these conditions are not candidates for hormone therapy:
Pregnancy or unexplained bleeding: these are temporary but absolute contraindications to hormone
therapy.
Past history of breast cancer or endometrial cancer: while usually considered contraindications to
hormone therapy, short-term use for severe menopausal symptoms may be considered with proper
precautions.
Return to Algorithm
Progestin if indicated
Estrogen-containing contraceptives
(Fettes, 1999 [Low Quality Evidence]; de Lignieres, 1996 [Low Quality Evidence]; Silberstein, 1993
[Low Quality Evidence])
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Algorithm Annotations
104. Successful?
Successful is commonly defined as a 50% reduction in frequency in headache days and/or severity of
headaches.
Return to Algorithm
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Clinicians should evaluate for vascular risk factors before prescribing estrogen
containing contraceptives for treatment of migraine.
Migraine aura
Smoking
Women who have migraine with an aura probably have significantly increased ischemic stroke risk if
estrogen-containing contraceptives are used. This risk probably increases with age as baseline stroke
rates increase, so that the increased risk may be acceptable to the younger patient (i.e., under age 30),
but not to the older patient. It is probably too simplistic to say that no patient with migraine with aura
should use estrogen-containing contraceptives. The decision should be individualized and should be
made with the patient.
It appears reasonable that women who have prolonged migraine auras (certainly those beyond 60 minutes),
multiple aura symptoms, or less common aura symptoms (i.e., dysphasia, hemiparesis) should be strongly
discouraged from using estrogen-containing contraceptives.
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Algorithm Annotations
Patients who develop a migraine aura for the first time while using estrogen-containing contraceptives, or
whose previous typical migraine aura becomes more prolonged or complex should discontinue estrogencontaining contraceptives.
Use of oral contraceptives in patients with a history of migraine increases the risk of stroke. [Conclusion
Grade II: See Conclusion Grading Worksheet B Annotation #111 (Risk of Stroke)]
Women with migraine aura who smoke and are hypertensive further increase their risk. Additional risk is
also noted if they are taking estrogen-containing contraceptives.
Return to Algorithm
Clinicians may prescribe prophylactic treatment for patients with migraine history
after realistic goals and expectations have been established with the patient.
Three or more severe migraine attacks per month that fail to respond adequately to symptomatic
therapy.
Less frequent but protracted attacks that impair the patient's quality of life.
Prophylactic therapy
Prior to instituting prophylactic therapy for migraine, it is imperative that realistic goals and expectations be established. Patients should have a clear understanding that the goals of preventive therapy
are to:
Decrease migraine attack frequency by 50% or more
Decrease pain and disability with each individual attack
Enhance response to acute, specific, anti-migraine therapy
One or more of these goals may be achieved.
Medications
The choice of prophylactic agent depends upon:
Side-effect profile
Comorbid conditions
Medication interactions
Evidence-based efficacy
Patients should also understand that there is usually a latency of at least three to six weeks between
the initiation of medication and recognizable efficacy. Often, an 8- to 12-week trial is necessary,
allowing an adequate period for drug titration to a dosage likely to attain efficacy. It is also not
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Algorithm Annotations
uncommon for initial side effects to subside after continued therapy, and patients should be made
aware of this so as to avoid premature discontinuation of a potentially effective medication.
The choice of prophylactic medication should be individualized according to the side-effect profile,
the presence of comorbid conditions and risk of medication interactions. For example, a tricyclic
antidepressant may be especially useful with a migraineur with depression, while sodium valproate
may be ideal for a patient with epilepsy.
Reinforce education and lifestyle management. Refer to Annotation #15, "Evaluate Type of Primary
Headache. Initiate Patient Education and Lifestyle Management."
Adolescents
As a prophylactic treatment topiramate, 100 mg/day was effective in reduction of the number of
migraine headaches a month (Lewis, 2009 [High Quality Evidence]).
Medications
The following references pertain to the medications used in prophylactic treatment.
Antiepileptics
Valproate sodium
(Hering, 1992 [High Quality
Evidence];
Klapper, 1997 [High Quality
Evidence])
Gabapentin
(Mathew, 2002 [High Quality
Evidence])
Topiramate
(Brandes, 2004 [High Quality
Evidence]; Silberstein, 2004
[High Quality Evidence])
Beta-Blockers
Atenolol
(Johannsson, 1987 [Low
Quality Evidence])
Tricyclics
Amitriptyline
(Couch, 1979 [High
Quality Evidence])
Metoprolol
Doxepin
Nadolol
Nortiptyline
Nebivolol
(Schellenberg, 2008 [High
Quality Evidence])
Propranolol
(Carroll, 1990 [High
Quality Evidence])
Timolol
Other Therapies
The treatment therapies listed below are in alphabetical order and do not indicate work group preference
or scientific support.
Acupuncture
A systematic (Cochrane) review of acupuncture in migraine prophylaxis demonstrated that adding
acupuncture to patients getting only acute treatment for headaches reduced the number of headaches
patients had. When true and sham acupuncture were compared, they both reduced the number of
headaches. There was no difference in benefit between true and sham acupuncture groups when
results for all trials were pooled. Acupuncture demonstrated slightly better outcomes and fewer
adverse effects than drugs shown to be helpful for prophylaxis (Linde, 2009 [Systematic Review]).
Biofeedback
Various methods of biofeedback have been used as adjunctive therapy for migraine and tensiontype headaches. A meta-analysis of 53 studies of biofeedback in combination with relaxation for
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Algorithm Annotations
tension-type headache demonstrated these to be more effective than headache monitoring, placebo
or relaxation, especially in reducing headache frequency. Most of these studies were randomized
controlled trials. Effects were most pronounced in adolecents (Nestoriuc, 2008 [Meta-analysis]).
Coenzyme Q10
In one randomized placebo-controlled trial, coenzyme Q10 was superior to placebo for attack
frequency, headache days and days with nausea (Sndor, 2005 [High Quality Evidence]).
Feverfew
This herbal therapy is made from crushed chrysanthemum leaves. 250 mcg of the active ingredient, parthenolide, is considered necessary for therapeutic effectiveness. Because these are herbal
preparations, the quantity of active ingredient varies with the producer (Vogler, 1998 [Systematic
Review]; Johnson, 1985 [High Quality Evidence]).
Magnesium
Daily oral dosages of 400 to 600 mg of this salt have been shown to be of benefit to migraineurs in
European studies (Peikert, 1996 [High Quality Evidence]).
Onabotulinum toxin
Onabotulinum toxin has been approved by the Food and Drug Administration for the treatment
of chronic migraine. Since this approach would be used by headache specialists or others trained
specifically for use of this product, onabotulinum toxin is beyond the scope of this discussion.
Physical therapy
Individuals unable to take medication or interested in other nonpharmacological headache management, may benefit from physical therapy including craniocervical exercises. Craniocervical exercises
designed to correct postural faults by retraining and strengthening craniocervical flexion, cervicothoracic extension, scapular retraction, thoracic extension and normalization of lumbar lordosis
have been shown to significantly reduce tension-type and cervicogenic headaches over a prolonged
time frame (van Ettekoven, 2006 [High Quality Evidence]; Jull, 2002 [High Quality Evidence]).
Relaxation training
Relaxation training includes progressive muscular relaxation, breathing exercises and directed
imagery. The goal is to develop long-term skills rather than to treat individual events. Repetitive
sessions and practice by the patient increase the success of these therapies in reducing headache
frequency (Reich, 1989 [High Quality Evidence]).
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Algorithm Annotations
Riboflavin
A randomized, placebo-controlled study has found daily supplements of 400 mg moderately effective in reducing the frequency and severity of migraine (Schoenen, 1998 [High Quality Evidence]).
Several additional treatment modalities are available. The modalities listed below lack sufficient
scientific support to be recommended as therapies of proven value.
Cervical manipulation
Previous studies suggested potentially high levels of risk associated with improper application of
this modality. Although some studies report few complications, the scientific evidence of significant benefit is not convincing. There is well-documented evidence of cerebral infarction and death
from cervical manipulation (Haldeman, 2002 [Low Quality Evidence]; Krueger, 1980 [Low Quality
Evidence]; Parker, 1980 [High Quality Evidence]). A systematic review demonstrates that numerous
deaths have been associated with high-velocity, short-lever thrusts of the upper spine with rotation
(Ernst, 2010 [Meta-analysis]).
Return to Algorithm
After 6-12 months, a gradual taper of prophylactic migraine treatment is recommended unless headaches become more frequent or more severe.
Return to Algorithm
A beta-blocker and tricyclic antidepressant may be more effective and produce fewer side effects in
combination than a single drug at a higher dose from either class.
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The Aims and Measures section is intended to provide protocol users with a menu
of measures for multiple purposes that may include the following:
population health improvement measures,
quality improvement measures for delivery systems,
measures from regulatory organizations such as Joint Commission,
measures that are currently required for public reporting,
measures that are part of Center for Medicare Services Physician Quality
Reporting initiative, and
other measures from local and national organizations aimed at measuring
population health and improvement of care delivery.
This section provides resources, strategies and measurement for use in closing
the gap between current clinical practice and the recommendations set forth in the
guideline.
The subdivisions of this section are:
Aims and Measures
Implementation Recommendations
Implementation Tools and Resources
Implementation Tools and Resources Table
46
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6. Decrease the percentage of patients with migraine headache who are prescribed opiates and barbiturates
for the treatment of migraines to less than 5%. (Annotations #36, 49)
Measure for accomplishing this aim:
a. Percentage of patients with migraine headache with a prescription for opiates or barbiturates for
the treatment of migraine.
7. Increase the percentage of patients with migraine headache who have appropriate acute treatment.
(Annotations #30, 32, 36)
Measure for accomplishing this aim:
a. Percentage of patients with migraine headache prescribed appropriate acute treatment.
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Measurement Specifications
Measure #1a
Percentage of patients diagnosed with primary headache using the appropriate diagnostic criteria.
Population Definition
Data of Interest
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older for which appropriate diagnostic criteria were used.
Denominator:
Number of patients age 12 years and older diagnosed with a primary headache.
Review electronic medical records for patients age 12 years and older with one of headache diagnoses:
migraine, tension-type, cluster, sinus or chronic daily headache. Determine whether appropriate diagnostic
criteria were used to determine diagnosis.
Notes
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Measure #2a
Percentage of patients with a primary headache who received educational materials on headache.
Population Definition
Data of Interest
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older with primary headache, who received educational
materials on headache. This can include information about:
Stress reduction, regular eating and sleeping schedules, and regular aerobic exercise
Treatment approaches
Denominator:
Review electronic medical records for patients age 12 years and older with a primary headache. Review
records to determine whether patients received written educational materials on headache.
Notes
Providing education is of paramount importance in managing any chronic illness; it is especially important
in the ongoing management of migraine. Patients may have to make lifestyle changes and are often required
to make self-management choices in the treatment of individual headaches and to maintain a diary to clarify
the frequency, severity, triggers and treatment responses to their headaches.
This is a process measure, and improvement is noted as an increase in the rate.
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Measure #3a
Percentage of patients with primary headache syndrome who are prescribed prophylactic treatment when
appropriate.
Population Definition
Data of Interest
# of patients who are prescribed prophylactic treatment when appropriate
# of patients with headache diagnosis
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older with primary headache syndrome who are prescribed
prophylactic treatment when appropriate.
Denominator:
Number of patients age 12 years and older with primary headache diagnosis syndrome.
Review electronic medical records for patients age 12 years and older with primary headache syndrome.
Review records to determine whether patients were prescribed prophylactic treatment when appropriate.
Notes
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Measure #4a
Population Definition
Data of Interest
Number of days per month with migraine for patients who are diagnosed with migraine headache.
Review electronic medical records for patients age 12 years and older with diagnosis of migraine headache.
Review records to determine the number of days per month the patients had migraine.
Notes
This is an outcome measure, and the goal is a decerease in days with migraine.
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Measure #4b
Percentage of patients with migraine headache who are showing improvement in functional status shown
by using one of the following disease-specific tools or questionnaires (e.g., MIDAS, Headache Impact Test
(HIT), Migraine Specific Quality of Life [MSQ])*.
* While general functional status/quality of life assessment tools are easier to administer, disease-specific
measures may be easier to interpret for disease-specific disability. Tools can be found at http://www.headaches.org.
Population Definition
Data of Interest
# of patients who are assessed for functional status using disease-specific tools
# of patients with migraine headache diagnosis
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older and migraine headache diagnosis, who are showing
improvement in functional status shown by using one of the following disease-specific tools
or questionnaires (e.g., MIDAS, Headache Impact Test, Migraine Specific Quality of Life).
Denominator:
Number of patients age 12 years and older with migraine headache diagnosis.
Review electronic medical records for patients age 12 years and older with migraine headache diagnosis.
Review records to determine whether patients were assessed for functional status using disease-specific
tools or questionnaires such as MIDAS, HIT or MSQ.
Notes
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Measure #4c
Percentage of patients with migraine headache seen for migraine in the emergency department/urgent care.
Population Definition
Data of Interest
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older and migraine headache diagnosis who are seen for
migraine in the emergency department/urgent care.
Denominator:
Number of patients age 12 years and older with migraine headache diagnosis.
Review electronic medical records for patients age 12 years and older with migraine headache diagnosis.
Review records to determine whether patients were seen for migraine in the emergency department/urgent
care.
Notes
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Measure #4d
Percentage of patients with decreased migraine headache shown by using a calendar or diary.
Population Definition
Data of Interest
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older and migraine headache diagnosis, who have headache calendar or diary.
Denominator:
Number of patients age 12 years and older with migraine headache diagnosis.
Review electronic medical records for atients age 12 years and older with migraine headache diagnosis.
Review records to determine whether patients reported having headache calendar or diary.
Notes
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Measure #5a
Population Definition
Data of Interest
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older and migraine headache diagnosis, who have a
treatment plan.
Denominator:
Number of patients age 12 years and older with a migraine headache diagnosis.
Review electronic medical records for patients age 12 years and older with migraine headache diagnosis.
Review records to determine whether patients had treatment plan.
Notes
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Measure #5b
Percentage of patients with migraine headache with a treatment plan who report adherence to their treatment plan.
Population Definition
Patients age 12 years and older with diagnosis of migraine headache and have a treatment plan.
Data of Interest
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older and migraine headache diagnosis and treatment
plan who report adherence to their treatment plan.
Denominator:
Number of patients age 12 years and older with migraine headache diagnosis and treatment
plan.
Review electronic medical records for patients age 12 years and older with migraine headache diagnosis
and treatment plan. Review records to determine whether patients report adherence to their treatment plan.
Notes
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Measure #6a
Percentage of patients with migraine headache with a prescription for opiates or barbiturates for the treatment of migraine.
Population Definition
Data of Interest
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older and migraine headache diagnosis who are prescribed
opiates or barbiturates for the treatment of migraine.
Denominator:
Number of patients age 12 years and older with migraine headache diagnosis.
Review electronic medical records for patients age 12 years and older with migraine headache diagnosis.
Review records to determine whether patients were prescribed opiates or barbiturates for the treatment of
migraine.
Notes
This is a process measure, and improvement is noted as a decrease in the rate to less than 5% usage in a
facility. This measure is intended to address overuse in prescription on opioids and narcotics for the treatment of migraine headache.
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Measure #7a
Population Definition
Data of Interest
Numerator/Denominator Definitions
Numerator :
Number of patients age 12 years and older and migraine headache diagnosis who are prescribed
appropriate acute treatment.
Denominator:
Number of patients age 12 years and older with migraine headache diagnosis.
Review electronic medical records for patients age 12 years and older with migraine headache diagnosis.
Review records to determine whether patients were prescribed appropriate acute treatment.
Notes
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Implementation Recommendations
Prior to implementation, it is important to consider current organizational infrastructure that address the
following:
Culture and the need to shift values, beliefs and behaviors of the organization.
The following system changes were identified by the guideline work group as key strategies for health care
systems to incorporate in support of the implementation of this guideline:
Develop a system for assessment of headache based on history and functional impairment.
Develop a system for results of this assessment to be used for identification of treatment options/
recommendations.
Develop systems that allow for consistent documentation and montoring based on type of headache.
Develop a system for follow-up assessment that identifies success in management of headache in
the primary care setting.
The author, source and revision dates for the content are included where possible.
The content is clear about potential biases and when appropriate conflicts of interests and/or
disclaimers are noted where appropriate.
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Title/Description
Audience
American Academy of
Family Physicians
Patients and
Families
http://familydoctor.org/familydoctor/en.html
Headache Care
http://www.headachecare.com
American Headache
Society (AHS)
Committee for Headache
Education
Healthfinder
Health Care
Professionals;
Patients and
Families
http://
www.americanheadachesociety.
org
http://www.healthfinder.gov
Patients and
Families
http://www.healthpartners.com
ICSI
Providers
http://www.icsi.org
Mayo Clinic
http://www.mayoclinic.com
Health Care
Professionals;
Patients and
Families
http://www.nlm.nih.gov/medlineplus
Patients and
Families
http://www.4woman.org
HealthPartners
Medical Group
National Library of
Medicine's MEDLINE
plus National
Institutes of Health
National Women's
Health Information
Center
National Headache
Foundation
http://headaches.org
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Author/Organization
Title/Description
Audience
Primary Care
Network
Health Care
Professionals
http://www.primarycarenet.org
Quality Metric
Incorporated
General health assessment tools including the Headache Impact Test (HIT).
(Need to register prior to
accessing information.)
Health Care
Professionals;
Patients and
Families
http://www.amihealthy.com
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Supporting Evidence:
63
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Design
Type
RCT
Author/Year
High
Quality
Population Studied/Sample
Size
Authors' Conclusions/
Work Group's Comments (italicized)
Work Group's Conclusion: Non-steroidal anti-inflammatory drugs should be considered approaches of first choice in the
prophylactic treatment of migraine associated with menses. Many clinicians consider triptans to be equally effective, but there
are no comparative studies.
65
Design
Type
Non
Random
Author/Year
Sances, Martignoni,
Fioroni, et al.
(1990)
Low
Quality
Population Studied/Sample
Size
Authors' Conclusions/
Work Group's Comments (italicized)
www.icsi.org
66
Low
Review
Becker (1999)
Quality
Low
Design
Type
Tzourio,
CaseTehindrazanaControl
rivelo, Iglsias, et
al. (1995)
Author/Year
Conclusion Grade: II
-Assumptions:
a. Women with migraine with aura have relative
stroke risk of approximately 6
b. Low-dose oral contraceptives with estrogen
content below 50 g have increased ischemic
stroke risk of approximately 2
c. If a patient with migraine with aura uses oral
contraceptives and if the odds ratios are multiplicative, the expected relative ischemic stroke risk
might be 6*2=12
-Expected incidence of ischemic stroke per
100,000 women per year:
Age
Without Migraine
Migraine with
Aura
No OC use OC use No OC use OC use
15-19 0.4
0.8
2
5
20-24 1.4
3
8
16
25-29 1.9
4
11
23
30-34 2.4
5
14
29
35-39 3.4
7
20
41
40-44 11.6
23
70
139
Primary Outcome Measure(s)/Results (e.g., pvalue, confidence interval, relative risk, odds
ratio, likelihood ratio, number needed to treat)
-Cases: 72 women under age 45 -Baseline characteristics: no differences in age,
BMI, history of diabetes, educational backyears hospitalized for first
ground, or hormonal content of oral contracepischemic stroke
tives; smoking status, oral contraceptive use
-Controls: 173 women who
status, and history of hypercholesterolemia difagreed to participate from
fered between groups
among 225 randomly selected
-No association between migraine and present
patients hospitalized in same
use of oral contraceptives in cases or controls
centers during same time for
-Migraine and ischemic stroke were strongly
acute orthopedic or benign
associated (60% of cases vs. 30% of controls;
rheumatological illness
p<0.001); association persisted after controlling
-Interviewed (telephone) cases
for age, history of hypertension, use of oral conand controls about history of
traceptives, and smoking
headaches and vascular risk
factors; subjects were not aware -In migrainous women using oral contraceptives
(at time of stroke for cases, at time of interview
of aim of study
for controls), risk of stroke was 13.9 (OR=13.9;
95%CI: 5.5-35.1) compared to those without
migraine not using oral contraceptive
Work Groups Comments: investigators used a structured interview to reduce potential for classification bias;
recall bias is possible
-Risk for ischemic stroke associated
with migraine without aura is probably
low enough that it is not a major consideration in prescribing oral contraceptives unless the patient has other
major risk factors or unless headaches
become substantially exacerbated
when oral contraceptives are started
-For patients with migraine with aura
or who develop migraine while taking
oral contraceptives, the additional
ischemic stroke risk should be considered in clinical practice
Authors' Conclusions/
Work Group's Comments (italicized)
Use of oral contraceptives in patients with a history of migraine increases the risk of stroke.
www.icsi.org
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Wendt J, Cady R, Singer R, et al. A randomized, double-blind, placebo-controlled trial of the efficacy
and tolerability of a 4-mg dose of subcutaneous sumatriptan for the treatment of acute migraine attacks
in adults. Clin Ther 2006;28:517-26. (High Quality Evidence)
Winner P, Ricalde O, Le Force B, et al. A double-blind study of subcutaneous dihydroergotamine vs
subcutaneous sumatriptan in the treatment of acute migraine. Arch Neurol 1996;53:180-84. (High
Quality Evidence)
Zhao C, Stillman MJ. New developments in the pharmacotherapy of tension-type headaches. Expert
Opin Pharmacother 2003;12:2229-37. (Low Quality Evidence)
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Note: As there are multiple, easy-to-access information sources available that contain current
detailed drug information, the tables on the following pages highlight only those selected
drugs, their dosing, side effect and contraindications that may be otherwise challenging to
locate. Therefore, this is not intended as an inclusive listing of medication treatment options.
All drugs are listed in alphabetical order, not in order of work group preference. Drugs are
listed by their generic names and include brand names only where the generic name may not
be well recognized. These drug treatment tables have been compiled from package inserts,
PDR.net and Micromedex.
When viewing the following Drug Treatment tables, please consider the following key for the
symbols used in each table:
* Patient, lying down supine, head extended 45 degrees and rotated 30 degrees, drips 0.4 mL of 4% lidocaine solution in the nostril ipsilateral to headache when unilateral, or most clear nostril when headache
is bilateral.
** Please note use of parenteral corticosteroids should be considered as treatment of last resort and
initiated only after careful consideration of the risks as they pertain to each individual. Their use is
empiric and based upon anecdotal evidence. The rationale for the use of corticosteroids is uncertain,
but they may reduce perivascular inflammation or sensitize the blood vessels to the vasoconstrictive
effect of circulating catecholamines and specific anti-migraine agents.
*** Ergotamine is not commonly used and not recommended as a first-line treatment.
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Drug
Dose
Chlorpromazine (CPZ)
Injection
Dexamethasone
Injection**
DHE
(dihydroergotamine
mesylate)
Injection
Side Effects
Drowsiness,
extrapyramidal
symptoms
Nausea, vomiting,
diarrhea, abdominal
cramps, dizziness,
paresthesia and leg
pain
Nasal spray
Nasal congestion,
throat discomfort,
nasal irritation,
nausea, chest
tightness, tingling,
vomiting
Hydrocortisone
Injection**
100-250 mg IM
Repeat parenteral or oral
equivalent may be given
within 24 hrs
2 by mouth at onset; 1 every
hr as needed; not to exceed
5 in 12 hrs; not to exceed 2
treatment days per week or
40 caps per month
0.4 ml-0.5 mL intranasally
over 30 seconds
Cushingoid
0.5-1 mg subcutaneous, IM
or IV, may repeat in 1 hour;
not to exceed 3 mg in 24
hours IM or 2 mg IV
Isometheptene Mucate
65 mg
Dichloralphenazone 100
mg
Acetaminophen 325 mg
Midrin CIV
Lidocaine 4% Solution*
Contraindications
Drowsiness,
dizziness
Burning or numbness
in nose or pharynx
Refer to the first page of Appendix A for the key explaining the symbols.
Many of the medications listed are available in a variety of formulations for different routes of administration (e.g.,
oral, intravenous, rectal suppository).
Basilar-type migraine is defined as free of the following features: diplopia, diparthria, tennitus, vertigo, transient
hearing loss or mental confusion (Headache Classification Subcommittee of the International Headache Society, 2004
[Guideline])
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Drug
Dose
Side Effects
Contraindications
Magnesium Sulfate
Injection
1 gm IV
Flushing,
hypotension,
burning sensation
in the face and
neck
Prochlorperazine IV
Drowsiness,
extrapyramidal
symptoms
Hypotension
Nausea, vomiting,
tremor, dizziness
Refer to the first page of Appendix A for the key explaining the symbols.
Many of the medications listed are available in a variety of formulations for different routes of administration (e.g.,
oral, intravenous, rectal suppository).
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Dose
Side Effects
Caffeine
Minimum 65 mg by mouth
Tremors, nausea
Metoclopramide
10 mg IV
Drowsiness, extrapyramidal
symptoms
Prochlorperazine
Drowsiness, extrapyramidal
symptoms
Promethazine
Drowsiness, extrapyramidal
symptoms
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Accurate diagnosis of primary headache requires a thorough physical exam and detailed headache history to rule out
secondary causes (e.g., hematoma, tumor, metabolic disorders, craniocervical arterial dissection, hydrocephalus, etc.).
Neuroimaging, EEG, lumbar puncture, or cerebrospinal fluid and blood studies may be indicated to evaluate for secondary
causes. These tests are not indicated for primary headache diagnosis.
Warning signs of possible disorder other than primary headache:
o Headaches that worsen over weeks or months
o Persistent headache brought on by cough, sneeze,
o New or different headache or "worst headache ever"
bending over, or physical or sexual exertion
o Sudden, severe onset or "thunderclap" headache
o Neurological signs suggestive of secondary cause:
o New onset of headaches after age 50
confusion, altered level of consciousness, memory
o Seizures
impairment, papilledema, visual field defect, cranial
o Symptoms suggestive of systemic disorder: fever,
nerve asymmetry, extremity weaknesses, clear
hypertension, myalgia, scalp tenderness, or weight
sensory deficits, reflex asymmetry, extensor plantar
loss
response, or gait disturbances
Cluster headache**:
o Frequency: one every other day to 8 per day
o Severe unilateral orbital, supraorbital and/or
temporal pain
o Pain lasting 15 to 180 minutes untreated
o One or more of the following occur on same side
as the pain:
Conjunctival injection
Lacrimation (tearing)
Nasal congestion
Rhinorrhea
Forehead and facial swelling
Miosis (constricted pupil)
Ptosis (eyelid drooping)
Eyelid edema
Agitation, unable to lie down
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Early treatment of migraines, using effective medications, improves a variety of outcomes, such as duration, severity, and
disability associated with chronic pain.
Long-term and first-line use of opiates and barbiturates should be avoided due to lack of studies to support effectiveness, side
effects, and potential for abuse.
Adjunctive therapy for all migraines:
Mild migraine treatment (self-management):
o Rest in quiet, dark room
o APAP/ASA/Caffeine
o IV rehydration
o ASA alone
o Antiemetics:
o Lidocaine nasal
Hydroxyzine
o Midrin
Metoclopramide
o NSAIDs
Prochlorperazine
o Triptans
Promethazine
Moderate migraine treatment:
o Caffeine
o DHE (dihydroergotamine mesylate)
Cluster headache treatment:
o Lidocaine nasal
o Acute treatment:
o Midrin
Oxygen
o NSAIDs
Sumatriptan SQ (self-management)
o Triptans
Zolmitriptan nasal (self-management)
Severe migraine treatment:
o Prochlorperazine
o Chlorpromazine
o DHE
o Ketorolac IM
o Magnesium Sulfate IV
o Triptans
DHE
Bridge treatment (for quick suppression of attacks until
maintenance treatment reaches therapeutic level):
Corticosteroids
Occipital nerve block
Maintenance treatment (for sustained suppression of
attacks over the expected cluster cycle):
Avoid alcohol during cycle
Verapamil
Steroids
Lithium
Depakote
Topiramate
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*Note: All information provided in this summary is for non-pregnant persons age 12 and over. Due to fetal risk and the complications
of medication management, pregnant women, those who desire to become pregnant, or those who are breastfeeding should be treated
based on the appropriate chronic pain and obstetrical guidelines.
** Other disorders have been ruled out, or if another disorder is present, the headaches did not start around the same time as the
disorder.
Used with permission by McKesson Health Solutions, 2012. The information contained in this Summary is based on the ICSI
guideline and is not a comprehensive review.
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ICSI has long had a policy of transparency in declaring potential conflicting and
competing interests of all individuals who participate in the development, revision
and approval of ICSI guidelines and protocols.
In 2010, the ICSI Conflict of Interest Review Committee was established by the
Board of Directors to review all disclosures and make recommendations to the board
when steps should be taken to mitigate potential conflicts of interest, including
recommendations regarding removal of work group members. This committee
has adopted the Institute of Medicine Conflict of Interest standards as outlined in
the report, Clinical Practice Guidelines We Can Trust (2011).
Where there are work group members with identified potential conflicts, these are
disclosed and discussed at the initial work group meeting. These members are
expected to recuse themselves from related discussions or authorship of related
recommendations, as directed by the Conflict of Interest committee or requested
by the work group.
The complete ICSI policy regarding Conflicts of Interest is available at
http://bit.ly/ICSICOI.
Funding Source
The Institute for Clinical Systems Improvement provided the funding for this
guideline revision. ICSI is a not-for-profit, quality improvement organization
based in Bloomington, Minnesota. ICSI's work is funded by the annual dues of
the member medical groups and five sponsoring health plans in Minnesota and
Wisconsin. Individuals on the work group are not paid by ICSI but are supported
by their medical group for this work.
ICSI facilitates and coordinates the guideline development and revision process.
ICSI, member medical groups and sponsoring health plans review and provide
feedback but do not have editorial control over the work group. All recommendations are based on the work group's independent evaluation of the evidence.
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84
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Acknowledgements:
All ICSI documents are available for review during the revision process by
member medical groups and sponsors. In addition, all members commit to
reviewing specific documents each year. This comprehensive review provides
information to the work group for such issues as content update, improving
clarity of recommendations, implementation suggestions and more. The
specific reviewer comments and the work group responses are available to
ICSI members at http://www.icsi.org/Headache.
The ICSI Patient Advisory Council meets regularly to respond to any
scientific document review requests put forth by ICSI facilitators and work
groups. Patient advisors who serve on the council consistently share their
experiences and perspectives in either a comprehensive or partial review of a
document, and engaging in discussion and answering questions. In alignment
with the Institute of Medicine's triple aims, ICSI and its member groups are
committed to improving the patient experience when developing health care
recommendations.
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87
Acknowledgements
Invited Reviewers
During this revision, the following groups reviewed this document. The work group would like to thank
them for their comments and feedback.
HealthPartners Health Plan, Minneapolis, MN
Lakeview Clinic, Waconia, MN
Marshfield Clinic, Marshfield, WI
Mayo Clinic, Rochester, MN
Medica Health Plan, Hopkins, MN
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Document Drafted
Jan May 1997
John Beithon, MD
Family Practice, Work Group
Leader
Lakeview Clinic
Rick Carlson, MS
Measurement Advisor
HealthPartners
Elizabeth Detlie, MD
Family Practice
North Suburban Family
Clinicians
David Dodick, MD
Neurology
Mayo Clinic
Chris Hult, MD
Family Practice
HealthPartners
First Edition
Aug 1998
Second Edition
Jun 2000
Third Edition
Jun 2001
Fourth Edition
Aug 2002
Fifth Edition
Aug 2003
Sixth Edition
Dec 2004
Seventh Edition
Feb 2006
Eighth Edition
Feb 2007
Ninth Edition
Apr 2009
Tenth Edition
Feb 2011
Eleventh Edition
Begins Feb 2013
Wendy Milligan
Health Education
HealthPartners
Chris Schroeder, RN
Facilitator
ICSI
Frederick Taylor, MD
Neurology
Park Nicollet Clinic HealthSystem Minnesota
Leonard Warren, MD
Family Practice
Quello Clinic
89
Since 1993, the Institute for Clinical Systems Improvement (ICSI) has developed more than 60 evidence-based
health care documents that support best practices for the prevention, diagnosis, treatment or management of a
given symptom, disease or condition for patients.
The information contained in this ICSI Health Care Guideline is intended primarily for health professionals and
other expert audiences.
This ICSI Health Care Guideline should not be construed as medical advice or medical opinion related to any
specific facts or circumstances. Patients and families are urged to consult a health care professional regarding their
own situation and any specific medical questions they may have. In addition, they should seek assistance from a
health care professional in interpreting this ICSI Health Care Guideline and applying it in their individual case.
This ICSI Health Care Guideline is designed to assist clinicians by providing an analytical framework for the
evaluation and treatment of patients, and is not intended either to replace a clinician's judgment or to establish a
protocol for all patients with a particular condition.
ICSI's medical group members and sponsors review each guideline as part of the revision process. They provide
comment on the scientific content, recommendations, implementation strategies and barriers to implementation.
This feedback is used by and responded to by the work group as part of their revision work. Final review and
approval of the guideline is done by ICSI's Committee on Evidence-Based Practice. This committee is made up
of practicing clinicians and nurses, drawn from ICSI member medical groups.
These are provided to assist medical groups and others to implement the recommendations in the guidelines.
Where possible, implementation strategies are included that have been formally evaluated and tested. Measures
are included that may be used for quality improvement as well as for outcome reporting. When available, regulatory or publicly reported measures are included.
Scientific documents are revised every 12-24 months as indicated by changes in clinical practice and literature.
ICSI staff monitors major peer-reviewed journals every month for the guidelines for which they are responsible.
Work group members are also asked to provide any pertinent literature through check-ins with the work group
midcycle and annually to determine if there have been changes in the evidence significant enough to warrant
document revision earlier than scheduled. This process complements the exhaustive literature search that is done
on the subject prior to development of the first version of a guideline.
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