M i g r a i n e a n d Te n s i o n - Typ e

Headache
Diagnosis and Treatment

Rebecca Burch, MD

KEYWORDS

Headache
Migraine
Migraine with aura
Tension-type headache
Treatment

Prevention
Nonpharmacologic treatment
Rescue treatment

KEY POINTS

The prevalence of migraine or severe headache in the last 3 months is 15.3% in the United
States; this includes 20.7% of women and 9.7% of men.

Migraine may be misdiagnosed as tension-type headache, sinus headache, or other
headache types. A diagnosis of migraine should be strongly considered for recurrent,
disabling headaches without red flags for secondary headache.

Tension-type headache typically responds to nonsteroidal antiinflammatory drugs or sim-
ple analgesics for acute treatment and tricyclic antidepressants for prevention.

Triptans are the mainstay of acute treatment for migraine and may be used in combination
with nonsteroidal antiinflammatory drugs, simple analgesics, or antiemetics.

Prevention should be offered when headaches are frequent or disabling, or when acute
treatments are overused or contraindicated. Topiramate, valproate, propranolol, meto-
prolol, and amitriptyline have the best evidence for efficacy. A new class of preventive
treatments, the calcitonin gene related peptide monoclonal antibodies, is now available.

INTRODUCTION

Migraine is a recurrent, often disabling headache with neurovascular

pathophysiology. It is highly prevalent in the United States and around the world,
affecting an estimated 37 million people in the United States and 1 billion people
worldwide.1 Migraine or severe headache in the last 3 months is reported by
15.3% of people in the United States.2 Migraine is more common in women
compared with men, with a prevalence of 20.7% in women and 9.7% in men.2
Migraine is most common during the ages of 18 to 50, a time of high potential
work productivity and family caregiving responsibilities.3 Migraine-related disability

Conflicts of Interest Statement: The author has no relevant conflicts of interest to disclose.
Department of Neurology, John R. Graham Headache Center, Brigham and Women’s Hospital,
Harvard Medical School, 1153 Centre Street, Suite 4H, Jamaica Plain, MA 02130, USA
E-mail address: [email protected]

Med Clin N Am - (2018) -–-

https://doi.org/10.1016/j.mcna.2018.10.003 medical.theclinics.com
0025-7125/18/ª 2018 Elsevier Inc. All rights reserved.
2 Burch

can therefore be significant. Economic losses owing to migraine-related disability are

attributable to both absenteeism and presenteeism, or decreased productivity even
during work days.4 US population-based studies suggest that lack of access to care,
incorrect diagnosis, and failure to prescribe acute and preventive treatments are all
barriers to optimal management of migraine.5
Tension-type headache is more prevalent than migraine. The epidemiology of
tension-type headache is less well-studied than that of migraine. The best avail-
able estimates suggest that about 40% of people in the United States have expe-
rienced tension-type headache in the last year.6 Because it is less severe,
however, it is less likely to be seen in health care settings and is associated with
less disability.7

DIAGNOSIS OF MIGRAINE AND TENSION-TYPE HEADACHE

The diagnostic criteria for migraine and tension-type headache are found in Table 1.8
Migraine is frequently mistaken for tension-type headache, and the Spectrum study
found that this was a common headache-related diagnostic error in primary care set-
tings.9 There are several sources of diagnostic confusion. The International Classifica-
tion of Headache Disorders criteria for migraine require only 2 of the 4 commonly seen
pain characteristics, which means that a bilateral and nonthrobbing headache can
meet the criteria for migraine if it is moderate to severe, worsens with physical activity,
and has the appropriate migraine accompanying features. Neck pain and provocation
by stress, which are sometimes thought to be associated with tension-type headache,
are common features of migraine as well. Neck pain is present in about two-thirds of
people with migraine and stress is one of the most commonly reported migraine
triggers.10,11
Migraine should also be considered when patients report a history of sinus head-
ache, “sick headaches” or headaches that have a strong menstrual relationship.
The Sinus, Allergy, and Migraine study found that 86% of patients who self-
reported a history of sinus headache met the criteria for migraine or probable
migraine.12 The authors noted that reported triggers were a common reason for misdi-
agnosis, with common triggers of migraine in this population including weather
changes, seasonal variation, and exposure to allergens.
Because migraine is common and frequently misdiagnosed, it is reasonable to err
on the side of diagnosing migraine if a headache is recurrent, disabling, and does
not have any red flags for secondary headache.9 Making an accurate diagnosis of
migraine leads to appropriate disease-specific treatment, which is more likely to be
effective.
Tension-type and migraine are both divided into subtypes according to headache
frequency.8 The headache is classified as episodic if present on fewer than 15 days
per month, or chronic if present 15 or more days per month. Episodic migraine may
increase in frequency and become chronic over time, a process called migraine chron-
ification or transformation. Chronic migraine has been associated with a higher burden
of comorbidity and disability.4

MIGRAINE WITH AURA

About one-third of people with migraines have at least some attacks associated
with migraine aura.3 The diagnostic criteria for migraine aura are found in Box 1.
Aura is a focal neurologic event with a discrete time course, typically preceding
the development of migraine headache.13 Migraine aura can also occur in the
absence of headache.8 Visual aura is the most common aura subtype and is
 Migraine and Tension-Type Headache 3

Table 1
Diagnostic criteria for migraine and tension-type headache

Headache Type Migraine Tension-Type Headache

Number At least 5 At least 10
of attacks
Duration 4–72 h (untreated 30 min to 7 d
or unsuccessfully treated)
Pain At least 2 of the 4: At least 2 of the 4:
characteristics Unilateral location Bilateral location
Pulsating quality Pressing or tightening
Moderate or severe (nonpulsating) quality
pain intensity Mild or moderate intensity
Aggravation by or Not aggravated by routine
causing avoidance physical activity such as
of routine physical walking or climbing stairs
activity (eg, walking
or climbing stairs)
Accompanying During headache at least Both of the following:
features 1 of the following: No nausea or vomiting
Nausea and/or vomiting No more than one of
Photophobia and photophobia or
phonophobia phonophobia

Adapted from International Headache Society (IHS). The International Classification of Headache
Disorders, 3rd edition (ICHD-3). Available at: https://www.ichd-3.org/. Accessed June 24, 2018;
with permission.

present in about 95% of people who get aura of any type.14 In addition to visual
aura, typical aura also includes sensory changes or dysphasic speech. Hemiplegic
migraine presents with an aura including motor weakness, and should be differen-
tiated from numbness by neurologic examination during the event. Aura should be
distinguished from migraine prodromal symptoms, such as mood changes, in-
crease or decrease in appetite, fatigue, or systemic autonomic symptoms.15 Blurry
vision is frequently reported by patients as a migraine accompanying symptom, but
can be differentiated from visual aura in that it typically lasts throughout the head-
ache or develops in association with worsened pain, and in that it typically involves
the whole visual field.16
Patients should not be given a diagnosis of migraine with aura if there is uncer-
tainty about symptoms, owing to treatment and cardiovascular risk implications.
Women with migraine with aura have a 2-fold increase in the risk of ischemic
stroke compared with women without aura.17 Because exogenous estrogen
also increases the risk of stroke, use of estrogen containing contraceptives (also
called combined hormonal contraceptives [CHCs]) is contraindicated in women
with migraine with aura.18,19 It is not clear whether modern, lower estrogen
dose CHCs are associated with the same level of risk.20 In the absence of data
supporting safety, it is reasonable to follow current guidelines. It is worth
noting that the absolute risk of stroke in this population remains low even with
use of CHCs, and an individualized assessment of risks and benefits is
appropriate. Situations in which it may be reasonable to use CHCs include a
lack of reliable or effective contraceptive alternatives, medical conditions that
benefit from hormonal regulation, or limiting side effects from progesterone-only
formulations.18
4 Burch

Box 1
Diagnostic criteria for migraine aura

1. Aura symptoms may be visual, sensory, speech and/or language, motor, brainstem, retinal
2. Symptoms should have at least 3 of the following characteristics

At least 1 aura symptom spreads gradually over 5 minutes or longer

Two or more aura symptoms occur in succession

Each individual aura symptom lasts 5 to 60 minutes

At least 1 aura symptom is unilateral

At least 1 aura symptom is positive

The aura is accompanied, or followed within 60 minutes, by headache

Adapted from International Headache Society (IHS). The International Classification of Head-
ache Disorders, 3rd edition (ICHD-3). Available at: https://www.ichd-3.org/. Accessed June 24,
2018; with permission.

WORKUP

Migraine and tension-type headache are primary headache disorders, or those that
are not caused by or attributed to another disorder. These are primarily clinical diag-
noses and there is currently no available serum, cerebrospinal fluid, or imaging test to
confirm a diagnosis of migraine or tension-type headache. Testing is instead used to
rule out potential underlying causes of secondary headache.21 A list of red flags that
should raise concerns for secondary headache is given in Box 2.22 There is no expert
consensus on a panel of serum tests for headache, but some considerations might
include an erythrocyte sedimentation rate and C-reactive protein in patients over
50 years of age, thyroid-stimulating hormone, vitamin B12 levels, testing for Lyme dis-
ease or other regional tick-borne illnesses, or iron studies where appropriate.21 The
yield of these tests is generally low and the possibility of false-positive results should
be considered. The most appropriate diagnostic test is typically neuroimaging.23 MRI
is preferred to computed tomography scanning owing to better assessment of

Box 2
Red flags that suggest secondary headache

History
“First or worst” headache
Risk factors for prothrombotic or immunocompromised state (eg malignancy, human
immunodeficiency virus infection, pregnancy)
Age less than 5 or greater than 50 years
Abrupt onset (thunderclap headache)
Change in headache character
Progressive worsening with lack of response to treatment
Positional worsening or improvement
Worsening with Valsalva or straining
Examination
Papilledema
Cognitive impairment
Fever, stiff neck
Focal neurologic deficits

Modified from Cady RK. Red flags and comfort signs for ominous secondary headaches. Otolar-
yngol Clin North Am 2014;47(2):294; with permission.
 Migraine and Tension-Type Headache 5

conditions that may mimic migraine such as intracranial neoplasm.23 The accumu-
lated radiation risk associated with multiple head computed tomography scans may
also not be negligible.24

TREATMENT OF TENSION-TYPE HEADACHE

Tension-type headache is by definition a mild to moderate headache and as such

often responds to over-the-counter analgesics.25 Guidelines from the European
Federation of Neurologic Societies found that the over-the-counter treatments acet-
aminophen, aspirin, ibuprofen, and naproxen had level A evidence (effective) for acute
treatment of tension-type headache, as did the prescription nonsteroidal antiinflam-
matory drugs (NSAIDs) ketoprofen and diclofenac.26 Caffeine, typically used in com-
bination preparations with NSAIDs, was rated level B (probably effective). Butalbital
combination analgesics and the acetaminophen, dichloralphenazone, and isomethep-
tene combination are also used for refractory tension-type headaches.27 Butalbital-
containing medications may contribute to increasing headache frequency when
used more than 2 days a week.28 Triptans are not effective for pure tension-type head-
ache. Some patients have headaches that meet criteria for migraine as well as head-
aches that are phenotypically consistent with tension-type headaches. In these
patients, the tension-type headaches are most likely a forme fruste of migraine and
often do respond to triptans.29
There are no guidelines to suggest when prevention should be started for tension-
type headache. It seems reasonable to consider starting prevention when headache
frequency reaches 2 days a week or more, but this largely depends on the level of
disability associated with the headaches and patient preference. Tricyclic antide-
pressants including amitriptyline have the best evidence for prevention of tension-
type headaches.26 Selective serotonin reuptake inhibitors have been studied but
have not been shown to have benefit over placebo or tricyclic antidepressants.30
The muscle relaxant tizanidine has also been shown to have some benefit.31 When
these treatments fail, preventives with evidence for efficacy in migraine are some-
times tried.

NONPHARMACOLOGIC TREATMENT AND LIFESTYLE MANAGEMENT FOR MIGRAINE

Nonpharmacologic treatments with evidence for efficacy for prevention of migraine

include thermal or electromyography biofeedback, relaxation training, and
cognitive–behavioral therapy.32 Some patients find that relaxation and biofeedback
practices may also help abort an early attack. The use of mindfulness-based stress
reduction, meditation, and acceptance and commitment therapy for the prevention
of migraine are also active areas of research.33
Positive lifestyle habits including regular exercise, maintaining adequate hydra-
tion, eating regular meals, and avoiding known triggers may reduce headache fre-
quency.34,35 Of these, sleep often has the greatest impact, and sleep duration
and quality should be assessed in any patient with bothersome headaches.36 Die-
tary interventions for the prevention of migraine are widely reported in the lay liter-
ature. Despite this, there are very few scientific studies supporting dietary restriction
or modification as a preventative strategy.37,38 If patients have noticed particular
food triggers, or are interested in trying a broader dietary intervention, dietary mod-
ifications can be made while keeping a headache diary to provide objective
evidence.39
Over-the-counter vitamin supplements and herbal preparations are often consid-
ered nonpharmacologic treatments. American Academy of Neurology guidelines
6 Burch

found that magnesium, feverfew, and vitamin B2 (riboflavin) had level B evidence for
efficacy and coenzyme Q10 was a level C for prevention of migraine.40 Petasites,
an extract from the butterbur plant, had level A evidence, but use of butterbur is
currently not recommend owing to reports of liver toxicity.41 Nonpharmacologic treat-
ments for migraine are summarized in Table 2.
There is increasing interest, particularly among patients, in medical cannabis and
cannabinoid treatments for migraine and other headache types. There is a paucity
of good quality evidence in this area, although some positive case reports have
been published.42 Anecdotally, many patients report an analgesic benefit from
marijuana use or the widely available cannabidiol oil. Marijuana use has been re-
ported as a risk factor for reversible cerebral vasoconstriction syndrome, which
causes cerebral vasospasm and can lead to ischemic or hemorrhagic stroke.43,44
There is also a lack of good information about safety in psychiatrically vulnerable
populations. Given this, it seems premature to recommend marijuana as a
treatment for migraine. At this time, the author does not recommend against use
for patients who find benefit from it, but does not recommend it as a treatment
either.

ACUTE TREATMENT OF MIGRAINE

Acute treatment, also called abortive or symptomatic treatment, is taken to relieve

the pain of a migraine attack. Classes of medications used for acute treatment of
migraine include simple analgesics such as acetaminophen, NSAIDs (both over the
counter and prescription), combination analgesics including the over-the-counter
aspirin/acetaminophen/caffeine combination and the prescription analgesics contain-
ing butalbital, serotonin receptor agonists (triptans), ergot derivatives (particularly
dihydroergomatine), and antiemetics.45 Several antiemetics have intrinsic antimigraine
properties, including metoclopramide, prochlorperazine, and promethazine.46 Butal-
bital and/or caffeine-containing combination analgesics are not recommended as
first-line agents owing to the risk of medication overuse headache.47,48 Opioids are

Table 2
Nonpharmacologic and behavioral treatments for migraine

Dose and
Treatment Frequency AHS or US Headache Consortium Level of Evidencea
CoQ10 75 mg TID or C
100 mg BID
Feverfew 6.25 mg TID B
Magnesium 500–600 mg/day B
Riboflavin 400 mg/day B
Thermal biofeedback B
combined with
relaxation training
Relaxation training B
Electromyographic B
biofeedback
Cognitive–behavioral B
therapy

Abbreviations: AHS, American Headache Society; BID, 2 times per day; TID, 3 times per day.
a
B 5 probably effective; C 5 possibly effective.
 Migraine and Tension-Type Headache 7

not recommended as a treatment for migraine except in very limited circumstances,

discussed elsewhere in this article.49 A summary of acute medication options for treat-
ment of migraine is listed in Table 3.
Many patients with migraine have milder subforms of the disease that respond well
to over-the-counter or nonspecific treatments.50 Most patients with more frequent
and severe migraine also have some less severe headaches that also respond to
these treatments.29 Patients with more severe migraines, which includes most pa-
tients who present to clinical settings, will require a prescription for a migraine-
specific therapy such as a triptan, or a prescription NSAID.50 Triptans are the first-
line treatments for migraine in most cases.51 Triptans should not be prescribed to
patients with a history of coronary artery disease or multiple risk factors for coronary
artery disease, patients who have coronary vasospasm, or who have poorly
controlled hypertension.52 selective serotonin reuptake inhibitor/serotonin and
norepinephrine reuptake inhibitor use is not necessarily a contraindication to starting
a triptan. Although concerns for serotonin syndrome led to a black box warning on
coprescription of these medication classes, the evidence for the existence of this
as a practical concern is very sparse.53 A recent large database study failed to
show a meaningful risk of serotonin syndrome in patients coprescribed a selective
serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor and a
triptan.54
There have been few head-to-head studies among triptans. Studies have found that
patients who do not respond to 1 triptan may have a better response to another.55 It is
not possible to predict which triptan will be most effective for a given patient and some
trial and error may be necessary. It is reasonable to try 3 or 4 different triptans before
switching to a different type of abortive therapy.
Triptans are generally well-tolerated. They may produce “triptan sensations,” feel-
ings of pressure, tightness, or flushing in the head, neck, or chest.56 Patients should
be counseled about the potential for triptan sensations when a triptan is initially
prescribed.
The goal of acute treatment, regardless of agent, is pain freedom.57,58 Many pa-
tients will report that their acute treatment “takes the edge off” or provides only partial
relief. This incomplete response to acute treatment is a risk factor for migraine chron-
ification and also increases the disability associated with a migraine attack.59 If a pa-
tient reports an incomplete response, treatment should be optimized by increasing
the dose of the acute treatment, recommending earlier use of treatment, switching
agents within or between classes, or combining different classes of treatments
(such as combining a triptan with an NSAID, antiemetic, or both). In patients with
nausea, migraine disability may also be reduced by use of an antiemetic.60 Although
many patients report improvement of nausea with relief from the headache, this is not
always the case and treatment of migraine pain and nausea should be considered
separately.
Many patients with migraine have both more and less severe headaches, particu-
larly as headache frequency increases. Two treatment approaches have been pro-
posed in this scenario. Stepped care is the practice of starting with a nonspecific
treatment such as acetaminophen or an over-the-counter NSAID, followed by a
migraine-specific therapy such as a triptan if the headache continues or escalates.
In stratified care, the patient is asked to predict whether the headache is likely to
be mild versus moderate or severe, and choose either a nonspecific treatment or a
migraine-specific treatment based on this prediction.61 Treatment outcomes are
consistently better when stratified care is used.62 Many patients still use stepped
care despite this, often out of concern for running out of their limited number of
8 Burch

Table 3
Acute treatments for migraine headache

AHS Level of
Dose and Evidence for
Medication Frequency Migrainea Notes
Simple analgesics and combination analgesics
Acetaminophen 1000 mg A For nonincapacitating attacks
Aspirin/acetaminophen/ 500/500/ A Risk of medication overuse,
caffeine 130 mg particularly with OTC
availability
Isometheptene/ 65/100/ B (for Intermittently available
dichloralphenazone/ 325 mg isometheptine
acetaminophen alone)
Butalbital/acetaminophen/ 50/325/ C High risk of medication overuse
caffeine 40 mg headache; risk of withdrawal
seizure with daily use of high
doses
Butalbital/caffeine/aspirin 50/325/ C High risk of medication overuse
40 mg headache; risk of withdrawal
seizure with daily use of high
doses
NSAIDs
Aspirin 500 mg A
Diclofenac 50, 100 mg A Dissolving powder may be more
effective than tablet form
Ibuprofen 200, 400, A
800 mg
Indomethacin 25–50 mg N/A High incidence of gastric
discomfort
Ketoprofen 100 mg B
Naproxen 500, 550 mg A Naproxen sodium may be more
effective than naproxen base
Triptans and ergot derivatives
Almotriptan 12.5 mg A May have a more benign side
effect profile
Eletriptan 20, 40 mg A
Frovatriptan 2.5 mg A Long acting; also used BID for
menstrual migraine
prophylaxis
Naratriptan 1.0, 2.5 mg A Long acting; also used BID for
menstrual migraine
prophylaxis
Rizatriptan 5, 10 mg A Also available in an orally
dissolving tablet
Sumatriptan PO 25, 50, A Most broadly covered by
100 mg insurance; also available as a
SQ 4, 6 mg rectal suppository
NS 5, 10,
20 mg

(continued on next page)

 Migraine and Tension-Type Headache 9

Table 3
(continued )
AHS Level of
Dose and Evidence for
Medication Frequency Migrainea Notes
Zolmitriptan PO 2.5, A Also available as an orally
5.0 mg dissolving tablet
NS 2.5,
5.0 mg
Dihydroergotamine NS 0.5– A Pretreat with an antiemetic
2.0 mg owing to a high incidence of
nausea
Opioids
Codeine/acetaminophen 25/400 mg B High risk of medication overuse
headache
Other opioids Other oral High risk of medication overuse
opioids not headache; avoid routine or
studied for first line use
acute
treatment
of migraine
Antiemetics
Metoclopramide 5, 10 mg N/A Less sedating than
phenothiazine antiemetics;
risk of akathisia reaction; may
reduce migraine pain
Ondansetron 4, 8 mg N/A Not sedating; no benefit for
migraine pain
Prochlorperazine PO 5, 10 mg N/A Risk of sedation, akathisia
PR 25 mg reaction; may reduce
migraine pain
Promethazine 12.5, N/A Risk of sedation, akathisia
25.0 mg reaction; may reduce
PR 25 mg migraine pain

Abbreviations: AHS, American Headache Society; BID, 2 times per day; N/A, not applicable; NS,
nasal spray; NSAIDs, nonsteroidal antiinflammatory drugs; OTC, over the counter; PO, orally; PR,
rectal suppository; SQ, subcutaneously.
a
A 5 established as effective; B 5 probably effective; C 5 possibly effective.

triptans each month. When possible, patients should be educated to treat with their
triptan first line if there is a reasonable possibility that the headache will be moderate
to severe.
Acute treatment is more effective when taken early in the attack.63 Animal and
human studies have found that triptans are less effective once central sensitization,
or the progression of neuronal activation from the periphery to the brainstem
pain nuclei as a migraine evolves, sets in. The clinical marker for central sen-
sitization is cutaneous allodynia, the feeling of burning pain to light touch of the
scalp.64

MEDICATION OVERUSE HEADACHE

The frequency of acute medication use should be limited to prevent the develop-
ment of medication overuse headache.65 Medication overuse is diagnosed when
10 Burch

a patient has headache more than 15 days per month and is taking a medication
that can cause medication overuse headache more than 10 days per month
(ergot, triptans, opioids, combination analgesics including butalbital containing an-
algesics, or any combination of different types of acute medications) or 15 days per
month (acetaminophen, NSAIDs).8 Opioids and butalbital-containing medications
are the medication classes most likely to contribute to medication overuse head-
ache.48 Many patients who have migraine or tension-type headache use acute
treatment very frequently. It is worth noting that withdrawal of the overused medi-
cation will result in improvement of the headache, indicating that the overused
medication is actually contributing to the headache, in only about 50% of cases.66
Despite this finding, migraine or tension-type headache and medication overuse
headache can be diagnosed in combination if the headache meets criteria for
both conditions.

RESCUE THERAPY AND TREATMENT OF STATUS MIGRAINOSUS

Rescue therapy is an important component of the migraine treatment plan for many
patients, particularly if accompanying nausea or vomiting are severe, symptoms
escalate rapidly, the migraine is present upon awakening, or if first-line acute treat-
ments are often unreliable.45 Routine planning for rescue treatment may prevent un-
expected days of migraine disability, emergency room visits, and the need for urgent
management of migraines outside of office visits. Box 3 lists rescue treatments for
migraine.
Nonoral routes of administration are favored for rescue therapy.67 The onset of ac-
tion is typically faster and treatment effects are more robust for parenteral and rectally
administered treatments than for oral treatments, and patients with severe vomiting
are typically unable to absorb oral treatments.68 Nasal sprays and orally dissolving
tablets are largely absorbed through the gastrointestinal tract and some patients do
not respond to them fully. Sumatriptan is available as a subcutaneous injection and
rectal suppository. Promethazine and prochlorperazine suppositories are helpful for
patients with vomiting or who find benefit from sleep, as sedation is a common side
effect. Indomethacin is also available as a suppository and may be helpful for patients
who respond well to NSAIDs. Dihydroergotamine nasal spray may be useful for pa-
tients who are not vomiting. Very rarely, it may be appropriate to use an opioid in a
responsive patient for whom use is infrequent and in whom use prevents the need
for urgent or emergency room care. There is no evidence to support use of any partic-
ular opiate for migraine. Butalbital combination medications may be used in the same
way.
The American Headache Society Guidelines for the acute treatment of migraine in
the emergency room found the best evidence for the use of subcutaneous sumatrip-
tan as well as intravenous metoclopramide and prochlorperazine.69 Steroids,
including dexamethasone, do not seem to be effective for the acute treatment of
migraine, but do decrease the risk of headache recurrence after discharge.70 A pa-
tient who has not used a triptan for their migraine attack should be offered subcu-
taneous sumatriptan first line. If the patient has already taken a triptan, a
combination of nonopioid treatments (migraine cocktail) such as metoclopramide
or prochlorperazine with diphenhydramine and ketorolac may be used as the
first-line treatment for migraine in the emergency room.71 Diphenhydramine is not
effective as monotherapy, but may prevent akathisia from other treatments.69 Intra-
venous dihydroergotamine is an effective migraine-specific treatment that is under-
used in the emergency room setting. Intravenous magnesium also has level B
 Migraine and Tension-Type Headache 11

Box 3
Rescue and emergency room treatments for migraine

Sumatriptan SQ 4, 6 mg
DHE NS 1 to 2 mg or IV 1 mg 1 or q8 hours, pretreated with an antiemetic, for several days
Promethazine or prochlorperazine PR 25 mg; prochlorperazine IV/IM 10 mg
Metoclopramide IV 10 mg
Indomethacin PR 50 mg
Sedating medications (diphenhydramine PO 25 mg, hydroxyzine PO 25–50 mg,
benzodiazepines)
Ketorolac IV/IM 30 to 60 mg
Valproate IV 400 to 1000 mg
Magnesium sulfate IV 1000 to 2000 mg, for migraine with aura
Steroids, either as an oral taper or an IV dose 1

Abbreviations: DHE, dihydroergotamine; IM, intramuscularly; IV, intravenously; NS, nasal spray;
PO, orally; PR, rectal suppository; SQ, subcutaneously.

evidence for efficacy as an acute treatment specifically for migraine with aura.69
Opioids, and particularly parenteral opioids, should be avoided as a first-line
therapy.49
Unremitting migraine for at least 72 hours is termed status migrainosus. The treat-
ment of refractory status migrainosus is not well-studied, but treatments sometimes
used include steroids, intravenous dihydroergotamine repeated every 8 hours for
several days (the Raskin protocol), or infusions of antiemetics such as valproate or
levetiracetam.72

PREVENTIVE TREATMENT OF MIGRAINE

Preventive therapy should be considered when acute treatment is insufficient. The

criteria for consideration of preventive therapy include moderate to severe headache
more than 4 times a month, overuse of acute medications, poor response to acute
treatment, situations where typical acute treatments are contraindicated, or if rarer
headaches are unusually debilitating or alarming (such as headaches with prolonged
severe aura).73 Preventive therapies are typically chosen based on evidence for ef-
ficacy, side effect profile, and comorbidities. The goals of preventive treatment are to
reduce headache frequency, duration, and severity; improve response to acute
treatment; decrease the need for acute treatment; and reduce overall headache
disability.74
Some patients may be hesitant to take a daily medication for treatment of an
episodic condition. A shared decision-making model, where the clinician acts as an
educator and patients are active partners in treatment decisions, is ideal when consid-
ering prevention.75 Where appropriate, patients can be provided with several options,
educated about evidence for efficacy and possible side effects, and given the oppor-
tunity to choose their treatment path. Obtaining patient buy in to treatment may
improve adherence, which is typically quite poor for migraine preventives.76 Patients
should be educated that complete headache freedom is rarely an obtainable goal and
that a decrease in headache-related disability is the target of treatment.
12 Burch

Table 4
Preventive treatments for migraine

AAN/AHS
Target Dose and Level of
Medication Frequency Evidencea Notes
Antidepressants
Amitriptyline 25–100 mg nightly A First line if comorbid insomnia;
side effects include sedation
and weight gain
Venlafaxine 75–150 mg/day B Consider if comorbid
depression; withdrawal
syndrome can be unpleasant
and is probably
underappreciated
Antihypertensives
Atenolol 50–100 mg/day B Well-tolerated; may cause
orthostasis and exercise
intolerance; unlike other beta-
blockers, contraindicated in
pregnancy
Metoprolol 25–100 mg BID A Well-tolerated; may cause
orthostasis and exercise
intolerance
Propranololb 40–120 mg BID (nightly A Well-tolerated; considered safest
dosing often used) preventive in pregnancy; may
cause orthostasis and exercise
intolerance
Candesartan 16 mg/day C Generally well-tolerated;
contraindicated during
pregnancy (category D)
Lisinopril 20 mg/day C Generally well-tolerated;
contraindicated during
pregnancy (category D)
Verapamil 120–360 mg/day U Strong impression of clinical
benefit despite level U rating;
generally well-tolerated;
may be particularly useful in
migraine with aura
Antiepileptic drugs
Topiramateb 50–200 mg/day (side A First line if weight gain is a
effects higher above concern; contraindicated
100 mg/day) during pregnancy (category D)
Gabapentin 900–2400 mg total daily U Strong impression of clinical
dose, divided BID-TID; benefit despite level U rating;
higher doses more some patients also report
effective benefit as an acute treatment
Sodium 500–1000 mg total daily A High side effect burden
valproateb dose including weight gain, hair
loss, hepatotoxicity, and bone
marrow suppression; rarely
used as a first-line treatment
for this reason;
contraindicated during
pregnancy (category X)

(continued on next page)

 Migraine and Tension-Type Headache 13

Table 4
(continued )
AAN/AHS
Target Dose and Level of
Medication Frequency Evidencea Notes
Other
Onabotulinum 155 units SQ, divided A (American FDA approved for chronic
toxin Ab between 31 injection Academy migraine only; trials for
sites, every 12 wk of episodic migraine were
Neurology conclusively negative
Guideline)
Memantine 10–20 mg/day or divided N/A Generally well-tolerated
BID
Erenumab 70–140 mg SQ monthly N/A Approved in May 2018;
data regarding long term
safety in clinical practice
not available yet; benign
side effect profile in clinical
trials
Fremanezumab 225 mg SQ monthly or N/A Approved in September
675 mg SQ quarterly 2018; data regarding long
term safety in clinical
practice not available yet;
benign side effect profile in
clinical trials
Galcanezumab 240 mg SQ first month, N/A Approved in September 2018;
then 120 mg SQ data regarding long term
monthly safety in clinical practice not
available yet; benign side
effect profile in clinical trials

Abbreviations: AAN, American Academy of Neurology; AHS, American Headache Society; BID, 2
times per day; FDA, US Food and Drug Administration; TID, 3 times per day.
a
A 5 established as effective; B 5 probably effective; C 5 possibly effective; level U: evidence is
conflicting or inadequate.
b
FDA approved for prevention of migraine.

Adherence may also be improved by starting preventive medications at a low dose

and increasing gradually to the target dose.77 There is evidence to suggest that people
with migraine may be particularly sensitive to medication side effects.78 An adequate
trial of prevention requires at least 2 months once the target dose is reached. Treat-
ment response should be monitored using a headache and medication use diary, a
disability scale, or other objective measure.
Most preventive treatments for migraine were originally developed as antide-
pressants, antihypertensives, or antiepileptic drugs. Other classes of treatments,
such as neurotoxins and monoclonal antibodies to calcitonin gene related peptide
(CGRP) or its receptor, are also used.79 The CGRP monoclonal antibodies (mAbs)
are the only class of currently used preventives developed specifically for treatment
of migraine (methysergide was the first such treatment but is no longer in use).80
CGRP is a widely distributed vasodilator that is intrinsically involved in the
pathophysiology of migraine. The CGRP mAbs target either the CGRP molecule
itself or the CGRP receptor. In a network metaanalysis, the CGRP mABs seemed to
be about as effective as other available preventive treatments, but have fewer side ef-
fects and are more convenient to use.81 There are some remaining uncertainties about
14 Burch

the long-term safety of these treatments, because the role of CGRP in other organ sys-
tems is not fully known.82 Owing to these concerns and the high cost of these treat-
ments, the CGRP mAbs are currently typically used for refractory migraine patients
rather than as first-line treatments.83
Evidence for the efficacy of preventive treatments for episodic migraine was
assessed in a 2012 guideline from the American Academy of Neurology and Amer-
ican Headache Society.84 Levels of evidence range from A (best) to U (unknown)
based on the number of good quality studies supporting use.84 Commonly used pre-
ventive therapies, doses, and notes about clinical use are given in Table 4. Canadian
and European Neurologic societies have also produced guidelines on this topic.85
There was agreement between the guidelines that valproate, topiramate, proprano-
lol, and metoprolol had the best ratings, with amitriptyline close to the top of the list
as well. These medications can therefore be considered good first-line treatments,
although valproate has a high side effect burden and cannot be used in women of
childbearing potential. In addition to the treatments described in the table, muscle
relaxants such as cyclobenzaprine and tizanidine, agents commonly used for other
pain disorders such as duloxetine and pregabalin, other tricyclic antidepressants,
and the antihistamine cyproheptadine (particularly for children) are sometimes
used as well.79 Timolol, although approved by the US Food and Drug Administration
for migraine prevention, is used very rarely in clinical practice.

CHRONIC OR REFRACTORY MIGRAINE

Patients with chronic migraine often have multiple comorbidities that contribute to
migraine chronification or disability, and suboptimal lifestyle habits may contribute
as well.86 Factors that may contribute to migraine chronification or persistence are
presented in Box 4. It is often necessary to address these comorbidities as a part
of the migraine treatment plan, in addition to targeting migraine pain and accompa-
nying symptoms.87 Multimodality care, possibly including psychiatry, sleep medicine,
physical therapy, and nutrition support, may be helpful. Treatment gains may initially
be modest, but over time incremental gains can add up to significant improvements in
quality of life.
Combinations of preventive measures may be considered in patients with refractory
migraine.88 This is particularly the case if a treatment is effective but has bothersome
side effects. For example, adding topiramate may mitigate the weight gain caused by
other preventives. In patients with chronic migraine, onabotulinum toxin A may also be

Box 4
Potentially modifiable factors that contribute to migraine chronification or persistence

High frequency of headache attacks

Poor response to acute treatment
Medication overuse
Excessive caffeine intake
Obesity
Obstructive sleep apnea
Stressful life events
Mood disorders
 Migraine and Tension-Type Headache 15

added.89 Withdrawing other preventives with partial benefit is not necessary when
starting onabotulinum toxin treatment.

SUMMARY

Migraine and tension-type headache are highly prevalent and migraine is associated
with significant work and family related disability. Migraine is underdiagnosed and it
reasonable to err on the side of migraine when there are diagnostic uncertainties. Bar-
riers to appropriate treatment of migraine include lack of access to providers, misdi-
agnosis, and disease-specific therapies not being prescribed. Acute, rescue, and
preventive treatment options are extensive, and new classes of treatments are either
available or in development.

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