Journal of Midwifery & Womens Health www.jmwh.

org
Review

Migraines in Women: Current Evidence for

Management of Episodic and Chronic Migraines
CEU
Angela Deneris, CNM, PhD, Peggy Rosati Allen, CNM, MS, WHNP, Emily Hart Hayes, CNM, DNP,
WHNP, Gwen Latendresse, CNM, PhD

Migraine headache is a disabling brain disorder that affects millions of women in the United States. Many migraine sufferers are undertreated. Both
inadequate treatment and overuse of abortive migraine medication can contribute to progression from episodic to chronic migraine disorders.
A significant number of migraine headaches or severity of episodic migraine headaches warrants treatment with prophylactic medications for
prevention. This clinical update reviews the pathophysiology and diagnosis of migraine headaches in women, discusses the efficacy of abortive
and chronic pharmacologic treatment, and examines strategies to prevent progression from episodic migraine to chronic migraine. A discussion
of treatment during pregnancy and lactation is included.
J Midwifery Womens Health 2017;00:116  c 2017 by the American College of Nurse-Midwives.

Keywords: migraine headache, primary care, triptan

CASE REPORT
J.K. is a 35-year-old woman who reports having 6 to 10 mi-
graine headaches with aura per month for the past 2 years.
Symptoms include visual aura, significant right side throb-
bing pain at the temple, nausea, and photophobia. She
treats the headaches with aspirin/acetaminophen/caffeine
(Excedrin) or ibuprofen (Advil) with minimal relief. Her
blood pressure was 128/74 mm Hg on presentation with a
pulse of 72 bpm, and she has no other health issues. Her
medical history is negative for hypertension, thyroid dis-
ease, depression, or anxiety. Her mother has a history of in-
frequent migraine headaches. She is a nurse working in an
intensive care unit 36 hours per week, and she works both
day and night shifts. She experienced her first migraine
after a stressful work event at the age of 24 years. Her first
episode presented with a visual aura, followed 30 minutes
later by severe pulsating pain on the right side of her fore-
head accompanied by nausea and photophobia. She was
treated in the emergency department with hydromorphone
(Dilaudid) 2 mg and promethazine (Phenergan) 12.5 mg
given intramuscularly, and these medications relieved the
headache. She subsequently experienced approximately
2 to 3 migraines per month, which were associated with
red wine, monosodium glutamate, bright lights, stress,
and/or inadequate sleep. During her 2 pregnancies at
ages 28 and 31 years, her migraine frequency increased
to 4 to 5 headaches per month, and she was treated with
acetaminophen-butalbital-caffeine (Fioricet). In the past
2 years, the frequency and severity of her headaches have
increased most likely due to stress, poor sleep hygiene, diet,
and dehydration. Her stressful life events include caring
for a disabled daughter and understaffing at work with a
demanding supervisor. She has difficulty falling asleep af-
Address correspondence to Angela Deneris, CNM, PhD, College of Nurs-
ing, University of Utah, 2000 East 10 South, Salt Lake City, UT 84112.
E-mail: Angela.deneris@nurs.utah.edu
ter a night shift and frequently wakes up. Her diet is high in
refined carbohydrates, sugar, and caffeine, and she drinks
about 32 ounces of water a day. She doesnt exercise due to
time constraints. A standardized depression inventory was
administered, and the results indicate she has no symptoms
of depression. At her visit today, her midwife prescribed
sumatriptan (Imitrex) 100 mg for abortive treatment of
episodic migraines to take as soon as the aura presents and
metoclopramide (Reglan) 10 mg to treat nausea as needed.
Additionally, topiramate (Topamax) 25 mg every day was
prescribed for prophylactic treatment for her frequent
migraines. Her midwife discussed lifestyle management
options to decrease the incidence of migraines, including
increasing her water intake to 64 ounces per day, changing
her diet to include more protein and less refined carbo-
hydrates and sugar, aerobic exercise 30 minutes per day,
improving sleep hygiene, and requesting a day-shift-only
schedule at work. She was seen in clinic 2 months later and
reported significant reduction in migraine frequency to
2 to 4 per month with topiramate and lifestyle changes.
Sumatriptan effectively treated her episodic migraines, and
she has not needed to take metoclopramide. The midwife
increased her topiramate to 50 mg daily to hopefully
further reduce the frequency of migraine episodes.
INTRODUCTION
Migraine headaches are a common disabling disorder that
negatively impact quality of life and productivity. Migraines
disproportionately affect women, especially during the repro-
ductive years with an average prevalence of 20.2% compared
to a 9.4% prevalence in men.1 Hormonal fluctuations in
women are significantly associated with migraine frequency.
More than half of women who suffer from migraines experi-
ence an increase in symptoms in conjunction with their men-
strual cycle typically occurring from 2 days before the onset
to day 3 of the menstrual period.2,3 Migraine frequency can
change during pregnancy, breastfeeding, and menopause.4

1526-9523/09/$36.00 doi:10.1111/jmwh.12626 
c 2017 by the American College of Nurse-Midwives 1
 Current evidence indicates that migraines are a brain disorder that is frequently underrecognized and undertreated by
clinicians.
Episodic migraines need to be effectively treated to prevent the condition from becoming chronic.
Triptans are a safer treatment option in pregnancy for migraines than acetaminophen-butalbital-caffeine (Fioricet).
Evidence-based antiepileptic and beta-blocker medications will provide approximately half of chronic migraine suffers
with a 50% reduction in migraine frequency.
OnabotulinumtoxinA (Botox) is the only FDA-approved treatment for chronic migraines.

Migraines are underrecognized and undertreated by
clinicians.5 Although 52.8% of persons with migraines present
to their primary care provider for treatment, 16.7% of mi-
graine sufferers will present to the emergency room, where
they are often treated with opiates such as ketorolac (Toradol)
and other medications that are suboptimal for long-term
treatment. It is important to manage and treat episodic mi-
graines effectively to prevent the condition from becoming
chronic.6,7
In 2011, Moloney and Johnson published a comprehen-
sive article in this journal that addressed the diagnosis and
management of migraine headaches,8 which remains a rele-
vant resource as there have been few new developments in
the treatment of migraines since its publication. The purpose
of this article is to briefly review new discoveries about the
pathophysiology of migraine headaches and the importance
of appropriately diagnosing and managing episodic migraines
to prevent chronic migraines. Additionally, current guidelines
for treating episodic migraine headaches with triptans during
pregnancy and breastfeeding and when to refer to a headache
specialist are addressed. Potential new treatment therapies
based on current knowledge about migraine pathophysiology
are highlighted.
PATHOPHYSIOLOGY
Migraines are more than a headache, and the pathophysiol-
ogy is not completely understood. Migraines are a complex
neurovascular brain disorder that affect multiple cortical, sub-
cortical, and brainstem areas of the brain. Historically, mi-
graines were thought to be secondary to extracranial blood
vessel dilation because carotid vessels are dilated during a
migraine attack and vasoconstricting drugs are some of the
most effective treatments. This theory was largely discred-
ited by Amin et al in 2013. In this study, participants in-
tracranial and extracranial arteries were evaluated by mag-
netic resonance angiography during a spontaneous migraine
headache without aura. Results indicated that although mi-
graine pain was not associated with extracranial arterial di-
lation, intracranial arterial dilatation does occur.9 Current
studies have shown that a complex neuronal dysfunction
leads to a migraine attack, with intracranial vasodilatation
causing leakage of plasma proteins, mast cell degranulation,
and neurogenic inflammation that then contributes to the
condition.10,11
The brain of a migraine sufferer is extremely sensitive
to changes in routine and disruption of homeostasis, or
physiologic equilibrium.12 Hypothalamic involvement is
thought to be the link to migraine prodrome. A migraine
is likely to occur in predisposed individuals as a result of
a hypothalamic and brainstem response to stressors such as
low blood sugar; dehydration; emotionally stressful events;
inadequate or disrupted sleep; reduced caffeine consump-
tion; hormonal changes with menstruation, pregnancy, and
perimenopause; weather changes; tyramine in red wine;
and food additives such as monosodium glutamate, ni-
trates, and aspartame.11,12 It is hypothesized that hypotha-
lamic neurons that regulate homeostasis and circadian cy-
cles are drivers of prodromal symptoms, firing preganglionic
parasympathetic neurons.13 Thus, it is now known that mi-
graines are, at least partially, a dysfunction in sensorimotor
processing.
Cortical Spreading Depression and the
Trigeminovascular Neuronal System
Cortical spreading depression (CSD) is a slow propagat-
ing wave of neuronal and glial depolarization that spreads
across the cerebral cortex followed by a suppression of brain
activity.11,14 The phenomenon of CSD has been implicated in
causing the aura associated with migraine attacks. CSD ini-
tiates activation of the trigeminovascular neuronal system.
The trigeminovascular system is a plexus of nociceptive nerve
fibers that innervate the pial, arachnoid, and dural blood ves-
sels as well as the meningeal artery and large cerebral ar-
teries. This system carries nociceptive information from the
meninges to the brain. In addition, the trigeminovascular
neurons conduct pain signals to the cortex via relay neu-
rons in the thalamus.13,15 Activation of the trigeminovascular
neuronal system during a migraine causes release of neuro-
transmitters, such as serotonin, acetylcholine, vasoactive in-
testinal peptide, calcitonin-gene-related peptide, and nitric
oxide. Several of these neurotransmitters are vasoactive and
can induce dilation of intracranial blood vessels (which causes
extravasation of plasma proteins) and release of inflammatory
mediators.16
Calcitonin-gene-related peptide (CGRP), a potent va-
sodilator present in the nerve endings of the neurons in the
trigeminovascular system, is released during a migraine. El-
evated levels of CGRP play a significant role in the central

2 Volume 00, No. 0, xxxx 2017

and peripheral pathways that cause a migraine by causing in-
tracranial vasodilation and by transmitting pain signals from
the trigeminovascular system to the central nervous system.
CGRP may also contribute to neurogenic inflammation. Cur-
rent research is investigating the use of CGRP antagonists as
a preventative treatment for migraines.15,17
Sensitization of Pain Response
Serotonergic stimulation plays a central role in migraine
pathophysiology by evoking powerful transmission of neu-
ronal signaling. When neurons in the trigeminovascular sys-
tem become hyperexcitable, the pain threshold is reduced,
and an increased pain response ensues. When trigeminovas-
cular neurons become sensitized repeatedly during migraine
headaches, the threshold for response can decrease and the
magnitude or response can increase, thereby increasing the
number of headaches with less stimulus, which results in
chronic migraine headaches.10
Pathophysiology of Medication Overuse Headaches
There is a risk of medication overuse headaches developing
if migraines become more frequent. The pathophysiology of
medication overuse headache is unclear; however, hyperex-
citability of neurons in the cerebral cortex and the trigemi-
nal system have been demonstrated.18 It may be difficult to
determine whether medication overuse headache is a cause
or effect of chronic migraines, and the International Clas-
sification of Headache Disorders, 3rd Edition (beta ver-
sion) recommends diagnosing both if someone meets the
criteria.19
Role of Hereditary Factors
There is a strong hereditary component to migraines,
and family history usually reveals a genetic predisposition.
Genome-wide genetic studies have identified 38 new genomic
loci, including the X chromosome for migraine headaches.20
Three of these genes regulate glutamatergic neurotransmis-
sion and may explain the neuronal hyperexcitability of the mi-
graine brain. These genes are expressed in the vascular and
smooth muscle tissue and further our understanding of the
pathophysiology of migraine headaches.11,2024 CSD has been
identified as having a genetic link as well.14,24
Associated Comorbidities and Risk of Ischemic
Stroke
Migraine headaches, epilepsy, and major depression have
been identified as comorbid conditions. It has been postulated
that these 3 disorders may have similar underlying neuronal
and/or serotonergic dysfunction in the brain, since many
medications for both epilepsy and depression can be utilized
to treat migraines.4,12,25
Finally, migraine headaches are associated with an in-
creased incidence of ischemic stroke, which is theoreti-
cally linked to an underlying mechanism of migraine, such
as prolonged CSD. Migraine headaches are associated with
increased risk for endothelial abnormalities and platelet
Journal of Midwifery & Womens Health r www.jmwh.org
hyperaggregability, also known contributors to increased risk
for ischemic stroke, although the mechanisms underlying the
associations are not understood.26,27 An association between
migraine headaches and antiphospholipid syndrome has been
cited in the literature with the observation that some indi-
viduals with antiphospholipid syndrome with refractory mi-
graines experience complete resolution of symptoms with
anticoagulant treatment.28
DIAGNOSIS AND SYMPTOMS OF MIGRAINE
HEADACHES
Migraine headaches are diagnosed via clinical history and
are considered to be a recurrent disorder. Symptoms present
over the course of several hours to days in 4 phases:
1) the prodrome, 2) the aura, 3) the headache, and 4)
the postdrome. Approximately 25% of migraine suffer-
ers will experience an aura with visual, sensory, speech
and/or language, motor, brainstem, or retinal symptoms.
Table 1 defines symptoms and criteria for diagnosing mi-
graine headache.2931
Episodic migraines occur on fewer than 15 days per
month for 3 months and can become chronic migraines if they
are undertreated or if medications are used too frequently,
which can cause medication overuse headaches. Chronic mi-
graines are defined as headache symptoms that occur at least
15 days per month, with migraine features on at least 8 days
per month for at least 3 months.12,29
Risk factors for progression of episodic migraines to
chronic migraines are older age, female gender, Caucasian,
low education and socioeconomic status, and a family his-
tory of migraine. Obesity, snoring, depression, and stressful
life events have also been noted as risk factors for developing
chronic migraines.7,11,19
It is not unusual for women presenting with migraine
headache to have comorbid conditions. Women who have mi-
graine have an increased incidence of epilepsy, depression,
anxiety, hypertension, cardiovascular disease, sleep disorders,
and gastrointestinal disorders such as Helicobacter pylori in-
fection, irritable bowel syndrome, gastroparesis, celiac dis-
ease, and alterations in microbiota and should be screened
for these disorders.3235 Headaches that suggest the presence
of a secondary cause or the rare hemiplegic, brainstem aura
and vestibular migraines warrant an immediate referral to
a headache specialist. Table 2 lists symptoms that indicate
additional evaluation is needed.
TREATMENT OF MIGRAINE HEADACHES
Successful treatment of migraine headaches involves
3 important components: 1) treatment of acute attacks
(abortive therapy), 2) prevention of subsequent episodic
attacks, and 3) mitigating the potential for episodic migraines
to progress to chronic migraines. Management of episodic
migraines focuses on abortive treatment of the headache
and associated symptoms. This is in contrast to the goal of
preventive therapies, which is to reduce the frequency and
severity of future migraine headaches. Clinician education
regarding identification of migraines and prompt initiation of
effective treatment is paramount to achieving these treatment
goals. In addition to pharmacologic treatment for acute and
3
 Table 1. Symptoms of Migraine Headaches and Criteria for Diagnosis
Migraine Phase
Prodrome
Symptoms may or may not precede headache
by several hours
Migraine without aura
Symptoms present at least 5 times lasting
4-72 hours (untreated or unsuccessfully
treated)
Migraine with aura
Symptoms present at least 2 times
Postdrome
Symptoms may or may not present after
resolution of the headache
Sources: Giffin N, et al,30 Giffin N, et al,31 Headache Classification Committee of the International Headache Society.29
chronic migraines, important treatment strategies include
helping the woman to maintain homeostasis by identifying
and avoiding specific triggers.
Abortive Treatments for Episodic Migraine
The US Headache Consortium recommends that migraine-
specific medications be used for migraine sufferers.36 How-
ever, only two-thirds of migraine sufferers who have sought
care from a health care provider are prescribed migraine-
specific treatments.37 In addition to nonpharmacologic strate-
gies, mild to moderate episodic migraines that occur only
a few times per month may respond to nonsteroidal anti-
inflammatory drugs (NSAIDs) or acetaminophen as first-line
abortive therapy.3840 Individuals with moderate to severe or
variable attacks who do not respond to these over-the-counter
treatments will likely require prescription migraine-specific
medications.38,40
Table 3 describes the dosage regimens, selection cri-
teria, US Food and Drug Administration (FDA) category,
and lactation risk for the abortive therapies for episodic
migraine.39,4143 The oldest medical abortive therapies for
migraine headaches were the ergot alkaloid derivatives
4 Volume 00, No. 0, xxxx 2017
Symptoms
Fatigue; depression; irritability; food cravings; yawning; muscle tenderness; neck
stiffness; abnormal sensitivity to light, sound, and smell
The following characteristics (2 or more):
Unilateral location
Pulsating quality
Moderate or severe pain intensity
Aggravated by or causing avoidance of routine physical activity
Symptoms during a headache (one or more):
Nausea, vomiting, or both
Photophobia and phonophobia
Symptoms listed above with fully reversible aura symptoms (one or more):
Visual
Sensory
Speech and/or language
Motor
Brainstem
Retinal
The following characteristics (2 or more):
One aura symptom occurring gradually over 5 minutes
Individual aura symptom lasting 5-60 minutes
One aura symptom is unilateral
Headache accompanies or follows aura within 60 minutes
Feeling drained or exhausted, difficulty concentrating, stiff neck, mild residual head
discomfort
ergotamine and dihydroergotamine, but these medications
are rarely utilized now since the significant discovery of sero-
tonin receptor agonists (5-HT1B/1D), known as triptans.44,45
NSAIDs and triptans are generally considered to be the
first-line abortive therapies for episodic migraine.38,40
Triptans are serotonin receptor agonists that effectively
abort migraine headache by increasing serotonin activity,
moderating the serotonin dysfunction, and diminishing com-
munication between peripheral and central trigeminovascu-
lar neurons, all of which are major contributors to migraine
headache.11,17,40 Triptans approved by the FDA for use in
the treatment of migraines are listed in Table 3. Triptans are
available in oral and oral disintegrating tablets and intranasal
and subcutaneous forms. Subcutaneous injections result in
the fastest relief for those who can tolerate an injection. Oral
tablets are easy to administer, and, in general, they have good
bioavailability. Oral dissolving tablets do not have to be taken
with water but have a slower onset of action.41 If nausea
and vomiting or decreased gastrointestinal tract function is
present, intranasal spray or subcutaneous injection may be a
better choice.
Because selective serotonin reuptake inhibitors (SSRIs)
and selective norepinephrine reuptake inhibitors (SNRIs)
 Table 2. Headache Requiring Referral to Headache Specialist
Vestibular migraine with brainstem aura (previously known as
basilar migraine): 2 attacks with 2 of the following reversible
symptoms:
Migraine with aura symptoms
Difficulty with speech/language symptoms
Vertigo
Tinnitus
Diplopia (double vision)
Ataxia (failure of muscle coordination)
Hemiplegic migraine: 2 attacks
Migraine with aura symptoms
Fully reversible motor weakness, numbness of the face and
hands, tremor, and unilateral muscle weakness or cognitive
symptoms such as attention deficit, difficulty finding words,
and transient amnesia
Status migraine:
A debilitating migraine with or without aura lasting 72 hours
Headaches attributed to a secondary cause
New headache onset after 50 years of age
Sudden onset of new severe headache
Worsening headaches in symptoms and/or frequency
Symptoms of ischemic stroke
New headache with a diagnosis of malignancy,
immunosuppression, or HIV
Headaches with symptoms of an intracranial infection such
as fever, stiff neck, or rash
Source: Headache Classification Committee of the International Headache
Society.29
increase serotonin activity as a mechanism of action, the FDA
has issued a warning regarding concurrent use of triptans with
an SSRI or SNRI secondary to the risk of serotonin syndrome,
a potentially life-threatening condition.46 However, serotonin
syndrome is unlikely to occur with infrequent use (1-2 times
per month) of a triptan for women who are also taking an SSRI
or SNRI. Common side effects of triptans include dizziness,
dry mouth, nausea, flushing, tingling of the skin, drowsiness,
chest heaviness/tightness, and weakness. Triptans should not
be used by women who have uncontrolled hypertension,
ischemic heart disease, coronary vasospasm, cerebrovascular
disease, peripheral vascular disease, and basilar or hemiplegic
migraine.47
Menstrual-related migraines without aura usually are
more severe and can be longer lasting and more diffi-
cult to treat.48 Long-acting triptans have been very effective
for menstrual-related migraines and are also described in
Table 3.41 Current guidelines typically caution against the
use of combined hormonal contraceptives in women with
migraines with aura due to increased risk of stroke.27
However, emerging evidence indicates that very-low-dose
(20-25 mcg) or ultra-low-dose (10-15 mcg) ethinyl estradiol
(EE)-containing formulations, when considered as an isolated
Journal of Midwifery & Womens Health r www.jmwh.org
factor, do not increase stroke risk in these women. Further-
more, continuous ultra-low-dose formulations may actually
decrease stroke risk through their potential to decrease the
frequency of migraine auras.49,50
Treatment for Episodic Migraines During Pregnancy
Although the number of migraine episodes may decrease
during pregnancy, hormonal changes in pregnancy may
exacerbate more severe migraine symptoms that require
pharmacotherapy. Many clinicians are hesitant to prescribe
triptans during pregnancy. However, research indicates that
these medications are likely to be safe for use during preg-
nancy. A meta-analysis that included 4208 infants born after
use of triptans during pregnancy found no increased risk of
major congenital malformations (odds ratio [OR], 0.84; 95%
confidence interval [CI], 0.61-1.16), prematurity (OR, 0.9;
95% CI, 0.35-2.30), or spontaneous abortions (OR, 1.27; 95%
CI, 0.58-2.79) compared to infants born to migraine sufferers
who had not used triptans during pregnancy.51 However, the
study documented a significantly increased risk of sponta-
neous abortion in triptan-exposed pregnancies compared to
pregnancies of unexposed nonmigraine sufferers (OR, 3.54;
95% CI, 2.24-5.59).
Acetaminophen/butalbital/caffeine is often prescribed for
migraine during pregnancy. As part of a large ongoing
population-based case-control study that evaluates the rela-
tionships between congenital anomalies and in utero expo-
sures, Browne et al identified infants with congenital heart
defects who were exposed in utero to butalbital (73/21,090).
The prenatal data from these children was compared to that
of infants born in the same time period (1997 to 2007) who
were exposed to butalbital in utero but who did not have
congenital heart defects (15/8358). The authors found 3-
to 5-fold increased odds of congenital heart defects in ex-
posed infants including tetralogy of Fallot (adjusted odds ra-
tio [aOR], 3.04; 95% CI, 1.07-8.62), pulmonary valve stenosis
(OR, 5.73; 95% CI, 2.25-14.62), and secundum-type atrial sep-
tal defect (OR, 3.06; 95% CI, 1.07-8.79).52 Given these find-
ings, triptans are a safer treatment for pregnant women com-
pared to traditionally prescribed acetaminophen/butalbital/
caffeine.
Chronic Migraine Treatment
Chronic migraine headaches have significant individual and
societal costs, ranging from diminished quality of life and
loss of productivity to work absenteeism and high health
care utilization.7,12,17 Up to 40% of episodic migraine suf-
ferers could benefit from prophylactic treatment. Migraine
prophylaxis should be offered to women who report at least
4 migraines per month that cause impairment in function, es-
pecially since this frequency of migraines greatly increases the
risk of developing chronic migraines.6,7
The frequent use of medications to treat episodic mi-
graine in women with chronic migraines increases the risk
of medication overuse headache.7 Studies indicate that
frequent use of episodic migraine medication leads to neural
adaptations that can result in permanent brain sensitization
and increase in the frequency of headaches, even after the
5
6
Table 3. Abortive Therapies for Episodic Migraine
Drug, Generic (Brand)
Triptans
Almotriptan (Axert)
Eletriptan (Relpax)
Frovatriptan (Frova)
Naratriptan (Amerge)
Rizatriptan (Maxalt)
Sumatriptan (Imitrex)
Volume 00, No. 0, xxxx 2017
Dosage
6.5, 12.5 mg oral tablets; usual dose
12.5 mg; repeat in 2 hours;
maximum dose 25 mg/day
20, 40 mg oral tablets; usual dose
40 mg; repeat in 2 hours;
maximum dose 40-80 mg/day
Oral: 2.5 mg; usual dose 2.5 mg;
repeat in 4 hours; maximum dose
5 mg/day.
Menstrual migraine prophylaxis:
2.5 mg PO bid 6 days, start 2
days before menses
1, 2.5 mg oral tablets; usual dose
2.5 mg; repeat in 4 hours;
maximum dose 5 mg/day
5, 10 mg oral and oral
disintegrating tablets; usual dose
10 mg; repeat in 2 hours;
maximum dose 20 mg/day
Oral 25, 50, 100 mg tablets; usual
dose 50 mg; maximum dose
200 mg
Subcutaneous: 4, 6 mg; usual dose
6 mg; maximum dose 12 mg/day
Intranasal: 5, 20 mg; usual dose 20
mg; maximum dose 40 mg/day
Repeat in 2 hours for all forms
Comments to Assist Selection
Half-life 3-4 hours
Half-life 4 hours; second choice
triptan for use during pregnancy
and breastfeeding
Long-acting triptan (26-hour
half-life); first choice for
prophylactic treatment of
menstrual migraine
Half-life 5-8 hours; effective in
prophylactic treatment of
menstrual migraine
Half-life 2-3 hours for all forms
Half-life 2 hours for all forms; first
choice triptan for use during
pregnancy and breastfeeding;
available as generic formulation
FDA Pregnancy
Risk Categorya LactMed Summary
FDA Category Cb No published data available
FDA Category Cb Limited information available; indicates that a maternal dose of up
to 80 mg daily produces low levels in breast milk and would not
be expected to cause any adverse effects in the breastfed infant,
especially if older than 2 months.
FDA Category Cb No published data available. Has a long half-life, so a shorter-acting
alternate drug may be preferred.
FDA Category Cb No published data available.
FDA Category Cb No published data available.
FDA Category Cb An exclusively breastfed infant would receive an estimated 3.5% of
the maternal weight-adjusted dosage.
Not expected to cause any adverse effects in most breastfed infants.
(Continued)
 Table 3. Abortive Therapies for Episodic Migraine
Drug, Generic (Brand)
Zolmitriptan (Zomig)
Journal of Midwifery & Womens Health r www.jmwh.org
Ergotamines
Dihydroergotamine
(Migranal)
Miscellaneous prescription medications
Acetaminophen with
butalbital and caffeine
(Fioricet)
Diclofenac (Voltaren)
7
Dosage
Oral and disintegrating tablets: 2.5,
5 mg; usual dose 2.5 mg;
maximum dose 10 mg/day
Intranasal: usual dosage 5 mg;
maximum dose 10 mg/day
Repeat in 2 hours for all forms
Subcutaneous: 1 mg/mL
Intranasal: 4 mg/mL (1 mL)
325 mg acetaminophen, 50 mg
butalbital, 40 mg caffeine
Oral tablet or powder: 50 mg 34
times/day; maximum 150
mg/day; single dose for powder
FDA Pregnancy
Comments to Assist Selection Risk Categorya LactMed Summary
Half-life 2.5-3 hours for all forms; FDA Category Cb No published data available.
also effective in prophylactic
treatment of menstrual migraine
No longer first-line; triptans are FDA Category Xd Limited data. Most authorities recommend against use during
now recommended as first-line breastfeeding.
therapy. Dihydroergotamine
possesses oxytocic properties
and therefore should not be
administered during pregnancy
One example of combination FDA Category Dc Limited data. Most authorities suggest that other agents are
analgesics; butalbital is a Increased risk for preferred during breastfeeding.
barbiturate with intermediate congenital heart
duration of action defects in
exposed fetuses
Half-life 2 hours Prior to 30 weeks: Limited data. Most consider diclofenac to be acceptable during
Avoid use during third trimester as FDA Category Cb breastfeeding, but other medications have more published
it may cause premature closure of Starting at 30 information and may be preferred.
the ductus arteriosus in the fetus weeks
gestation: FDA
Category Dc
(Continued)
8
Table 3. Abortive Therapies for Episodic Migraine
FDA Pregnancy
Drug, Generic (Brand) Dosage Comments to Assist Selection Risk Categorya LactMed Summary
Over-the-counter medications: Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs)

Acetaminophen (Tylenol)
Aspirin
Ibuprofen (Advil)
1000 mg q 4 hours, maximum 4
g/day
Oral or effervescent tablet:
975-1000 mg q 4-6 hours;
maximum 5.4 g/day
Oral: 400 mg q 4 hours; maximum
2400 mg/day
Half-life 2 hours; warning:
acetaminophen overdose is
associated with liver toxicity and
failure, and death
Maximum 24-hour dosage is 3-4g
in a 24-hour period
Many common over-the-counter
medications contain
acetaminophen. Advise against
concurrent use with other drugs
and substances with known liver
toxicity, ie, alcohol consumption
Half-life 2 hours
Half-life 2 hours
Avoid use during third trimester as
it may cause premature closure of
the ductus arteriosus in the fetus
FDA Category Cb Good choice for analgesia in breastfeeding women.
An exclusively breastfed infant would receive an estimated 1.1% of
the maternal weight-adjusted dosage.
Adverse effects in breastfed infants appears to be rare.
FDA Category Dc Best avoided during breastfeeding. Reye syndrome is associated
with aspirin administration to infants.
Prior to 30 weeks: Extremely low levels in breast milk. No known effects on
b
FDA Category C breastfeeding infants. Preferred choice as an analgesic in
Starting at 30 breastfeeding women.
weeks
gestation: FDA
Category Dc

(Continued)

Volume 00, No. 0, xxxx 2017

 Table 3. Abortive Therapies for Episodic Migraine
FDA Pregnancy

Journal of Midwifery & Womens Health r www.jmwh.org

Drug, Generic (Brand) Dosage Comments to Assist Selection Risk Categorya LactMed Summary
Naproxen (Aleve) Oral: 500-550 mg; (up to 825 mg) Long half-life (14 hours) Prior to 30 weeks: Limited data. Low levels in breast milk and uncommon side effects
twice a day; maximum 1375 Avoid use during third trimester as FDA Category Cb in breastfeeding infants. However, because of long half-life and
mg/day it may cause premature closure of Starting at 30 reported serious adverse reaction in a breastfed infant, other
the ductus arteriosus in the fetus weeks agents are preferred for newborns and preterm newborns.
gestation: FDA
Category Dc

Abbreviations: FDA, Food and Drug Administration; PO, oral.

a
New FDA Rule will replace FDA Risk Categories (A, B, C, D, and X) with Pregnancy Risk Summary, effective for all new drugs approved after June 2015. Labeling for drugs approved prior to 2015 (includes all medications in this table) will be
phased in gradually.
b
FDA Category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential
risks.
c
FDA Category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite
potential risks.
d
FDA Category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use
of the drug in pregnant women clearly outweigh potential benefits.
Sources: Marmura MJ et al,39 Loder E,41 LactMed,42 US Food and Drug Administration Approved Drug Products.43

9
medication is discontinued.53,54 Recommendations to pre-
vent medication overuse headache include limiting the use
of triptans, ergot alkaloids, mixed analgesics, and opioids to
no more than 10 days per month; limiting simple analgesics
or NSAIDS to no more than 15 days per month; and limiting
the combined use of more than one medication to no more
than 10 days per month.7
Chronic Migraine Prophylaxis
More than 40 medications have been used for migraine pro-
phylaxis without adequate evidence to provide clear guide-
lines for efficacy, dosage, or duration of treatment.7,36 Most
medications used to prevent migraines are not curative
and have variable rates of effectiveness and significant side
effects.6 Antiepileptic drugs and beta blockers are the most
frequently prescribed medications for migraine prophylaxis.55
Recent studies indicate that antiepileptic and beta-blocker
medications provide approximately half of treated patients
with a 50% reduction in migraine frequency.7,17 The 2012
American Headache Society and American Academy of Neu-
rology Migraine Prevention Guidelines provide an evidence-
based reference for prescription of specific antiepileptic and
beta-blocker medications as either effective (Level A) or prob-
ably effective (Level B) for migraine prophylaxis and are listed
in Table 4.6,7,4143
Beta blockers were incidentally discovered as effective
for treatment of headaches when first used to treat angina.56
The theoretical modes of action include interference with
adrenergic pathways from inhibition of central beta recep-
tors, interaction with serotonin receptors, and direct sero-
tonergic effects.56 The central nervous system side effects of
beta blockers include drowsiness, fatigue, sleep and memory
disturbances, and depression.56
The mechanisms of action of antiepileptics, such as dival-
proex sodium (Depakote) and valproate sodium (Depacon),
in migraine prophylaxis are also poorly understood. Effective-
ness of valproic acid (Depakene) may be related to the drugs
enhancement of the gamma-aminobutyric acid (GABA) ac-
tivity in the brain and/or the impact on the serotonin
communication system.56 Topiramates (Topamax) effective-
ness has been attributed to blockage of voltage-dependent
sodium channels, increase in GABA activity, antagonism of
glutamate receptors, and inhibition of carbonic anhydrase
enzyme.57
OnabotulinumtoxinA (Botox) was granted FDA approval
in 2010 for treatment of chronic migraines in adults and is
currently the only approved treatment for chronic migraine
prophylaxis.6 OnabotulinumtoxinA, a neurotoxin produced
by Clostridium botulinum, is administered by a trained spe-
cialist through intramuscular injections of the head and neck
muscles every 12 weeks.7 In a double-blind, placebo ran-
domized controlled trial, onabotulinumtoxinA was found to
be significantly more effective than placebo in reducing fre-
quency of migraine days compared to placebo (1.8 days
mean difference; 95% CI, 2.52 to 1.13) and is well tolerated
with minimal side effects.6 OnabotulinumtoxinA ultimately
prevents or mitigates the central sensitization that causes mi-
graine pain through its antinociceptive effect on trigemi-
novascular neurons, direct inhibition of peripheral neuron
10
sensitization, and blocked release of neurotransmitters and
neuropeptides.6
OnabotulinumtoxinA is classified as Category C for use in
pregnancy because there is limited evidence regarding safety.
There is one case report in the literature of its successful use as
migraine prophylaxis during pregnancy without any adverse
effect on the woman or her child, who was followed until age
6 years.58 It is not known if onabotulinumtoxinA is excreted
in breast milk; however, since the doses used medically are far
lower than those that cause botulism, amounts ingested by the
breastfed infant, if any, are likely insignificant.59
COMPLEMENTARY AND ALTERNATIVE
THERAPIES
Transcranial magnetic stimulation (TMS) is a safe, noninva-
sive, tolerable, and effective way to treat symptoms. An ex-
ternal pulsed magnetic stimulator induces electrical current
within the brain. The current may change levels of neurotrans-
mitters, depolarize neural tissue affecting neuronal excitabil-
ity, and disrupt CSD.60,61 A 2010 study by Lipton et al (N =
164) used either TMS or sham stimulation to treat persons
with migraines. Participants reported a significantly higher
rate of being pain free 2 hours later with TMS (39%) compared
with sham stimulation (22%).62 TMS can be utilized for both
acute and preventive migraine treatment. These devices may
be purchased on the Internet; however, they can vary widely in
price, degree of current delivered, and quality when obtained
via an online source.
Most women with migraine headaches are abnormally
sensitive to bright light, fluorescent lighting, and computers.
The retinal ganglion cells of the eye are photosensitive and are
intrinsically involved in the pathophysiology of photophobia.
The use of tinted eyeglasses that block blue-green and red light
has been shown to effectively reduce the number and severity
of migraine headaches.6365
Current evidence indicates that acupuncture may be an
effective complementary treatment for some migraine suf-
ferers. Although long-term studies are lacking, a review of
22 randomized trials evaluating the effectiveness of acupunc-
ture for the treatment of migraines found that after 6 months
of treatment, acupuncture was at least as effective as prophy-
lactic medications in decreasing migraine frequency (59% vs
54%, respectively; relative risk [RR], 1.11; 95% CI, 0.97-1.26).
In 12 trials of 1646 participants that compared the effect of
true versus sham acupuncture, participants treated with true
acupuncture had at least a 50% reduction in headache fre-
quency compared to a 41% decrease in those who received
sham acupuncture.66
Mindfulness-based meditation has been utilized in pain
management for years. Several small-study results indicate
that migraine headache severity and duration and quality of
life improve with consistent meditation.6769 Massage, restora-
tive yoga, and physical therapy could be recommended as well.
Feverfew, Coenzyme Q10, and magnesium supplements
have been studied, and results indicate that they reduce the
frequency and severity of migraine headache symptoms.7072
The mechanism of action of these supplements is unknown.
Feverfew is contraindicated in pregnancy since it is known to
inhibit platelet aggregation and prostaglandin production.73
Volume 00, No. 0, xxxx 2017
 Table 4. Pharmacotherapies for Chronic Migraine Prophylaxis
Drug, Generic (Brand)
Antiepileptic drugs
Valproate products
(Valproate sodium
[Depacon], Valproic acid
[Depakene, Stavzor],
Divalproex sodium
[Depakote])
Journal of Midwifery & Womens Health r www.jmwh.org
Topiramate (Topamax)
Beta blockers
Metoprolol (Lopressor)
Propranolol (Inderal)
Timolol
11
Dosage
250 mg twice a day
Divalproex available in
delayed release: 250 mg
twice a day;
maintenance dose up to
1000 mg/day
Extended release: 500 mg
once daily 1 week,
then up to 1000 mg/day
for maintenance
25-200 mg/day
47.5-200 mg/day
120-240 mg/day
10-15 mg twice a day
Comments to Assist Selection
Half-life 9-16 hours
Extensive list of common side effects and adverse
effects (10% or more of patients), including
gastrointestinal, hepatic, nervous system,
hematologic, respiratory, cardiovascular,
dermatologic, genitourinary, metabolic,
musculoskeletal, ocular, and psychiatric
Half-life 21 hours
Higher level of evidence for effectiveness
Half-life 3-4 hours
Side effects: Drowsiness, fatigue, sleep and memory
disturbances, and depression
Half-life 10 hours
Side effects: Drowsiness, fatigue, sleep and memory
disturbances, and depression
Half-life 4 hours
Side effects: Drowsiness, fatigue, sleep and memory
disturbances, and depression
FDA Pregnancy
Risk Categorya LactMed Summary
FDA Category Xd Low levels in breast milk; theoretical risk for infant
hepatotoxicity; some recommend monitoring
infant serum drug levels, platelets, and liver
enzymes during therapy for breastfeeding woman.
FDA Category Dc Limited data. Maternal dose of up to 200 mg daily
produces relatively low levels in infant serum.
Infant plasma levels about 10%-20% of maternal
plasma levels.
Monitor infant for diarrhea, irritability, adequate
weight gain, and developmental milestones.
FDA Category Cb Low levels in breast milk (0.5% of womans
weight-adjusted dosage), not expected to cause
adverse effects in breastfed infant. No special
precautions.
b
FDA Category C Trivial amounts in breast milk (0.1 and 0.9% of
weight-adjusted maternal dosage). Not expected
to cause any adverse effects in breastfed infants.
No special precautions required.
b
FDA Category C Limited data; other agents may be preferred,
especially for the newborn or premature infant.
(Continued)
12
Table 4. Pharmacotherapies for Chronic Migraine Prophylaxis
FDA Pregnancy
Drug, Generic (Brand) Dosage Comments to Assist Selection Risk Categorya LactMed Summary
Miscellaneous
OnabotulinumtoxinA; 0.1 mL (5 Units) Administration by trained medical specialist FDA Category Cb No data exist for use during breastfeeding; however,
Botulinum type A injections per each site. amounts ingested by an infant, if any, are expected
(Botox) Injections should be to be insignificant and not cause any adverse
divided across 7 effects in breastfed infants. No special precautions
specific head/neck required.
muscle areas; repeat
injections every 12
weeks

Abbreviation: FDA, Food and Drug Administration.

a
New FDA Rule will replace FDA Risk Categories (A, B, C, D & X) with Pregnancy Risk Summary, effective for all new drugs approved after June 2015. Labeling for drugs approved prior to 2015 (includes all medications in this table) will be phased
in gradually.
b
FDA Category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential
risks.
c
FDA Category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women
despite potential risks.
d
FDA Category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use
of the drug in pregnant women clearly outweigh potential benefits.
Sources: Aurora SK et al,6 Lipton RB et al,7 Loder E,41 LactMed,42 US Food and Drug Administration Approved Drug Products.43

Volume 00, No. 0, xxxx 2017

Coenzyme Q10 and magnesium do not have any known
adverse impact on pregnancy and lactation if used in the
recommended doses.
FUTURE MIGRAINE THERAPIES
Unfortunately, only about a third to half of migraine suf-
ferers will remain headache free after 24 hours when using
triptans.74 The need to develop more effective pharmaco-
logic treatments for migraine prevention is imperative.17,56
Developing therapies to treat chronic migraines is difficult
due to the lack of predictive animal models and lack of fund-
ing for market research in this area. As noted, CGRP is a
strong vasodilator of cerebral arteries and is located in the
sensory nerve endings. Studies are under way to develop
monoclonal antibodies that act as CGRP antagonists, and
these have shown efficacy for acute migraine therapy.11 Intra-
venous treatment with dihydroergotamine mesylate (DHE),
an ergotamine, has been utilized for migraine treatment for
more than 50 years but has unpleasant side effects and is
contraindicated during pregnancy. Dihydroergotamine me-
sylate is a vasoconstrictor with affinities for the dopamine,
noradrenaline, and 5-hydroxytryptamine receptors. Results
from studies of inhaled dihydroergotamine mesylate indicate
that it treats migraine symptoms effectively with fewer side
effects and should be available soon.75,76 Nitric oxide antag-
onist monomethyl arginine (L-NMMA) has demonstrated a
60% reduction of pain with episodic migraines.17 Genetic re-
searchers anticipate that improved understanding of the ge-
netics of migraine headaches will help develop new treat-
ments and enable clinicians to identify treatments that will be
effective for individual patients.17
CLINICAL IMPLICATIONS
Ineffective treatment of migraine headaches increases the risk
of developing chronic headaches, as demonstrated in this case
study. It is important to obtain a comprehensive history to ac-
curately diagnose migraine headaches when women present
with symptoms that suggest migraine as part of the differen-
tial diagnosis. A comprehensive history should include family
history, attack history with triggers and symptoms, medica-
tion history, and medical history. Headache diaries have been
recommended in the past; however, this may be an unneces-
sary step that delays effective therapy for women who meet In-
ternational Headache Society criteria for migraine diagnosis.8
Most women will have already unsuccessfully tried over-the-
counter medications.
There was a missed opportunity during the case
studys pregnancy to educate J.K. about migraines and the
lifestyle changes that may have helped her. She was given
acetaminophen-butalbital-caffeine (Fioricet) during her
pregnancy, which is frequently prescribed today despite
evidence that it should be avoided in pregnancy. Triptans
are effective and should be considered safe for use during
pregnancy and lactation.
Abortive Treatments
As primary care providers, midwives are qualified to di-
agnose and treat episodic and chronic migraines with the
Journal of Midwifery & Womens Health r www.jmwh.org
medications listed in the tables in this article, dependent
upon their prescriptive authority. Oral triptans are first-
line therapy for abortive treatment; however, effective treat-
ment may require a trial of more than one triptan, as some
women may not tolerate the side effects or obtain ade-
quate symptom relief from one triptan but do quite well
on another.39 Choosing which triptan to prescribe will be
based on cost, tolerability, individual migraine characteris-
tics, and contraindications.40 Women should be taught not
to wait until the migraine is severe before using abortive
medication, but to initiate therapy with the first symptoms
of a migraine headache. If a woman is taking an SSRI or
SNRI, triptans should be avoided if the medication is needed
more than 2 times per month due to the risk of serotonin
syndrome.
Evolving evidence indicates that a lower-dose estrogen
(25 mcg EE)-containing hormonal birth control is safe for
women with menstrual migraines with aura and that continu-
ous ultra-low-dose formulations (10-15 mcg EE) may actually
decrease stroke risk by reducing aura frequency.48,49 Women
who experience menstrual-related migraine with aura should
be offered a long-acting triptan preventatively for 6 days, start-
ing 2 days before menses, rather than continuous combined
contraception alone.41,48
Education about medication overuse headache from as-
pirin/acetaminophen/caffeine, opiates, triptans, and NSAIDs
is essential. If a woman is experiencing 4 or more migraines
per month that cause functional impairment, preventative
medication should be offered, as well as referral to a headache
specialist for women who experience 15 or more headaches
per month.
Prophylaxis Treatments
The selection of preventative medication should be made on
a case-by-case basis with consideration for the womans in-
dividual circumstance. If comorbid conditions exist, selec-
tion of a medication that has the potential to prevent mi-
graines and treat the comorbid condition is preferred to min-
imize the potential of adverse drug interactions and other
polypharmacy effects. For example, propranolol effectively
treats chronic migraines and may be a preferred first-line ther-
apy in a woman who also has hypertension and anxiety, but
should be avoided in women with peripheral vascular disease,
baseline bradycardia, or low blood pressure. Careful consider-
ation should be made to avoid medications that have a risk
of adverse fetal or neonatal effects in pregnant and breast-
feeding women and in women planning a pregnancy. With
additional education about the pharmacology of the pro-
phylaxis medications for chronic migraines, midwives may
prescribe these medications, onabotulinumtoxinA being the
exception.
Education about brain sensitivity and the need to main-
tain homeostasis by attention to adequate hydration, a nutri-
tious diet, sleep hygiene, and stress reduction are vital com-
ponents of effective migraine treatment. Borsook et al state
that . . . the brain is a plastic organ,12 and interventions de-
signed to restore homeostasis can prevent the transformation
of episodic migraines to chronic migraines by mitigating the
damaging effects on brain structure and function that can be
13
caused by an inadequately treated migraine.12 A comprehen-
sive free online application called My Migraine Buddy can
be an effective self-help tool to assist the migraine sufferer to
track headaches, identify triggers, determine individualized
lifestyle contributors, and connect with others via an online
community of support.
CONCLUSION
Migraine headache is a significant problem for women due
to its prevalence, debilitating nature, and the frequency with
which the disorder is unrecognized and undertreated. Failure
to diagnose and adequately treat episodic migraines leads to
unnecessary suffering and increased risk of chronic migraine,
which is more difficult to treat. Therefore, it is imperative
that midwives recognize migraine headaches in their clients
and provide appropriate treatment, with an emphasis on mi-
graine prevention, using both pharmacologic and nonphar-
macologic modalities. Midwives are likely to care for women
during their reproductive years, when hormonal fluctuations
can act as migraine triggers, increasing the frequency and
severity of episodic migraines. Treatment of migraine in preg-
nancy presents a unique challenge. Current evidence indicates
that triptan use in pregnancy may be a safe option, with care-
ful consideration of risks and benefits, especially during the
first trimester.
AUTHORS
Angela Deneris, CNM, PhD, FACNM, is Professor, Clini-
cal, University of Utah, faculty in the Nurse-Midwifery and
Womens Health Nurse Practitioner Programs, and is in clin-
ical outpatient practice with Birth Care Health Care.
Margaret Rosati Allen, CNM, MS, WHNP, is Assistant
Professor, Clinical, University of Utah, faculty in the Nurse-
Midwifery and Womens Health Nurse Practitioner Programs,
and is the Case Manager for Birth Care Health Care.
Emily Hart Hayes, CNM, DNP, WHNP, is Professor, Clini-
cal, University of Utah, faculty in the Nurse-Midwifery and
Womens Health Nurse Practitioner Programs, and is in full-
scope practice with Birth Care Health Care.
Gwen Latendresse, CNM, PhD, FACNM, is Associate
Professor, University of Utah, Program Specialty Director
of the Nurse-Midwifery Program, faculty in the Womens
Health Nurse Practitioner Program, and is in clinical
outpatient practice with Birth Care Health Care.
CONFLICT OF INTEREST
The authors have no conflicts of interest to disclose.
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