71-1

71
minimal efficacy of her present abortive therapy with naratriptan.
She is taking valproic acid for migraine prophylaxis, which is con-

CHAPTER 71
tributing to weight gain. When selecting abortive and prophylactic
therapies for this patient, consideration should be given to her

MIGRAINE HEADACHE
Oh, My Aching Head! Level II
Susan R. Winkler, PharmD, BCPS
medical history as well as to selection of a medication that has a
rapid onset and long duration of effect, is tolerable, and is easy to
administer, taking into account the patients preference for oral
medications. Finally, drug interactions and adverse events must be
considered. Rizatriptan and topiramate are reasonable therapeutic
alternatives for this patient as abortive and prophylactic agents.

INSTRUCTORS GUIDE TO
CHANGES IN THIS EDITION
CASEBOOK
Patient Presentation
Revised history of present illness (patient complains of men-
strually related migraines), social history (started smoking cig-
arettes due to increased stress), and patient assessment.
INSTRUCTORS GUIDE
Problem Identification
Revised based on changes in the patient presentation.
Migraines occur around the time of menses; the patient is a
cigarette smoker. The patients Migraine Disability Assessment
(MIDAS) score is 15 (increased from 12), which is Grade III,
moderate disability.
Information added about a Food and Drug Administration
(FDA) alert concerning concomitant use of triptans and SSRIs
or SNRIs.
Desired Outcomes
Addition of goal to decrease menstrually related migraines.
Therapeutic Alternatives
Information added on available dosage forms of the triptans.
Information removed about potential use of COX-2 inhibitors
(celecoxib) and topiramate for abortive treatment of migraine
headaches.
Information updated regarding the use of carbamazepine and
gabapentin for prophylaxis of migraines.
New information added on therapeutic options for prophylaxis
of menstrual migraines.
Optimal Plan
Updated information on the use of topiramate for prophylaxis
of menstrual migraines.
Patient Education
New question and answer added on patient education about
migraine triggers.
References
Revised and updated; six new references added.
CASE SUMMARY
A 34-year-old woman presents to the Neurology Clinic for a
follow-up visit for migraines. The patient complains of increased
migraine frequency, especially around the time of menses, and
Migraine Headache
Effective treatment of the nausea and vomiting that may accom-
pany migraines is as important as treating the headache itself. Use
of a headache diary is an effective means of monitoring the patients
response to therapy.
QUESTIONS
Problem Identification
1.a. Create a list of the patients drug therapy problems at this
clinic visit.
Migraine with aura with a recent increase in frequency from
two per month to as many as five per month because of stress-
ful events in her life, primarily a new full-time job and young
children.
Increased frequency of migraines occurring around the time
of menses.
Minimal efficacy of the abortive agent (naratriptan).
Nonadherence and unwanted weight gain with prophylactic
therapies (propranolol and valproic acid, respectively).
Depression is a chronic, stable problem that seems to be ade-
quately treated with sertraline. Sertraline efficacy should be
monitored.
Cigarette smoking one ppd; smoking relapse appears to be due
to the recent increase in stress.
1.b. Calculate the patients MIDAS score and describe the severity
of her migraine headaches. (See Fig. 71-1 for MIDAS ques-
tionnaire.)
This patients MIDAS score is 15 (Grade III, moderate disabil-
ity).
The MIDAS questionnaire is a validated five-item question-
naire to determine the severity of the patients migraine head-
aches. It addresses limitations in activities at work and home as
well as with social and leisure activities. The score is a sum of
missed days of activities at work and home and days in which
productivity was reduced by half over a 3-month period. Two
additional questions are not included in the total but are used
to assess headache frequency and intensity of pain. The first
question assesses the number of days that the patient experi-
enced headaches within the previous 3 months, and the second
question uses a pain scale to evaluate the headaches.
There are four grades of scores: Grade I (sum of 05), minimal
or infrequent disability; Grade II (sum of 610), mild or infre-
quent disability; Grade III (sum of 1120), moderate disability;
and Grade IV (sum of 21 or greater), severe diability.1
1.c. What clinical information is consistent with a diagnosis of
migraines in this patient?
She describes unilateral, throbbing headaches that are preceded
by an aura of flashing lights, nausea, and vomiting in severe
cases.

Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

71-2
The patient also describes associated symptoms of photopho-
bia and phonophobia.
SECTION 6
The headaches occur more frequently around the time of men-
ses.
1.d. Could any of the patients problems have been caused or
exacerbated by her drug therapy?
Overuse of agents typically used for symptomatic relief of
migraine can cause medication overuse headache. Simple anal-
gesics, combination analgesic products, ergotamine, and the
Neurologic Disorders
triptans may cause rebound or medication overuse head-
ache.2 Treatment includes patient education and discontinu-
ation of the offending agent(s). However, this patient is not
presenting with daily diffuse headaches, which are characteris-
tic of medication overuse headaches.
The use of SSRIs for migraine therapy has not been well
addressed in the literature. Although fluoxetine has demon-
strated some benefit in preventing migraines, it has also been
implicated as a possible cause of migraine with aura. Because
this patients headaches have occurred for the past 5 years and
she has only recently begun taking sertraline, it is unlikely that
sertraline is adversely affecting her headache status.
However, she intermittently takes naratriptan, which enhances
serotonin activity. There is the potential for a pharmacody-
namic interaction because both sertraline and naratriptan
enhance serotonergic neurotransmission. A US FDA alert was
issued in 2006 concerning the concomitant use of triptans and
SSRIs or SNRIs after a review of 27 case reports.3 Debate con-
tinues regarding the role of the triptans in causing seroton-
ergic syndrome.4 Signs and symptoms of excess serotonergic
activity include nausea, weight loss, ataxia, sexual dysfunction
(predominantly in males), alterations in cognition (e.g., dis-
orientation, confusion), behavioral changes (e.g., agitation,
restlessness), autonomic dysfunction (e.g., diarrhea, diapho-
resis), and neuromuscular activity (e.g., myoclonus, hyperre-
flexia). Patients experiencing serotonergic overload (serotonin
syndrome) usually respond to discontinuation of the impli-
cated drug(s) along with supportive care. In extreme cases,
treatment with antiserotonergic agents such as propranolol
may be necessary.
Desired Outcomes
2. What are the goals of therapy for this patient?
Identify alternative agents that she can use as abortive and pro-
phylactic treatments.
Relieve the nausea associated with the migraine attacks.
Identify stress management options for her.
Decrease the frequency of menstrually related migraines.
Enhance her quality of life, allowing her to return to normal
daily activities.
Therapeutic Alternatives
3.a. What pharmacotherapeutic alternatives are available for
treatment of the patients nausea, and how will they impact
potential abortive therapies?
For some patients, the extreme nausea and vomiting associ-
ated with the headache can be more disabling and demoral-
izing than the headache pain itself and can directly influence
the effectiveness of subsequent abortive agents. The following
items need to be considered when evaluating options for reliev-
ing nausea and/or vomiting associated with migraine:
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
Is an aura present or has the headache pain started?
Not all people experience or can identify an aura.
Approximately 1520% of migraine patients report
an aura. Although the presence of an aura may signal
impending migraine pain, it may also limit or affect the
timing of abortive drug administration.
In some instances, symptoms experienced during an aura
may limit treatment if nausea and/or vomiting are a com-
ponent. These may preclude the administration of an oral
abortive agent early during the attack without first using
an antiemetic.
Can the gastroparesis associated with migraine attacks be
problematic for the administration of abortive therapies?
Gastroparesis can limit the bioavailability of some oral
abortive agents. Both simple analgesics and oral non-
steroidal anti-inflammatory drugs may have decreased
absorption during migraine attacks.
Can the antiemetic be administered by a method other than
the oral route?
If nausea and/or vomiting are present, administration of
an antiemetic may be necessary. If the patient has severe
vomiting, parenteral and rectal routes of administration
should be considered.
Treatment options and concerns:
Antihistamine antiemetics (e.g., dimenhydrinate, hydroxyzine)
can be given orally or parenterally. These agents cause seda-
tion, which may or may not be advantageous. While this class
of drugs might be a reasonable choice to alleviate the patients
nausea, they will not treat and may worsen gastroparesis, which
could limit the bioavailability of some oral abortive therapies.
Phenothiazine antiemetics (e.g., chlorpromazine, prochlorpera-
zine, or promethazine) can be administered parenterally,
rectally, and orally. Each may effectively relieve nausea and
provide some direct headache relief, but will likely cause seda-
tion. In general, they do little to alleviate gastroparesis if an oral
abortive agent is desired.
Metoclopramide is a good adjunct to many abortive therapies
not only to reduce nausea but also to provide some direct
headache pain relief. Added benefits of metoclopramide
are that it can be administered orally or parenterally and it
enhances gastrointestinal motility, increasing the efficacy of
some oral abortive agents. Parenteral metoclopramide can
rapidly reverse gastroparesis, but oral dosage forms do not
provide immediate relief.
For this patient in whom nausea is a problem both during
her aura and with her migraine, oral metoclopramide has
been prescribed to be taken at the start of her migraine. The
patient does not require the parenteral or rectal routes of
administration because oral metoclopramide is effective in
resolving her nausea.
3.b. What pharmacotherapeutic alternatives are available for the
abortive treatment of this patients migraine attacks?
In general, migraine attacks that have a fast onset (less than1
hour), or that are associated with severe nausea or vomiting,
may not respond to oral agents. Commonly prescribed agents
used for abortive therapy include those listed below. This list
should not be considered all-inclusive.
Acetylsalicylic acid (oral).
Acetaminophen (oral).
Ibuprofen (oral).

Naproxen sodium or naproxen (oral; naproxen sodium is
absorbed faster than naproxen).
Isometheptene/dichloralphenazone/acetaminophen (e.g., oral
Midrin; limit use to 2 days per week; do not take more than five
capsules within a 12-hour period).
Aspirin/butalbital/caffeine (e.g., oral Fiorinal; limit use to 2 days
per week).
Acetaminophen/butalbital/caffeine (e.g., oral Fioricet; limit use
to 2 days per week).
Metoclopramide (oral or IV; risk of dystonic reaction).
Indomethacin (e.g., Indocin rectal).
Serotonin 5-HT1 receptor agonists (limit use to 2 days per week;
screen patients for asymptomatic cardiac disease; do not use
if an ergotamine derivative has been administered within 24
hours; do not use almotriptan, rizatriptan, sumatriptan, and
zolmitriptan with recent use of monoamine oxidase-I [MAO-
I] [within the past 2 weeks] because they are metabolized by
MAO).
Sumatriptan (Imitrex 25-, 50-, and 100-mg oral tablets, 4- and
6-mg subcutaneous injection, or 5- and 20-mg nasal spray)
Naratriptan (Amerge 1- and 2.5-mg oral tablets)
Zolmitriptan (Zomig 2.5- and 5-mg oral tablets, Zomig-ZMT
2.5- and 5-mg orally disintegrating tablets and 5-mg nasal
spray)
Rizatriptan (Maxalt 5- and 10-mg conventional oral tablets
and Maxalt-MLT 5- and 10-mg rapidly dissolving mint-
flavored wafers that can be placed on the tongue and taken
without water)
Almotriptan (Axert 6.25- and 12.5-mg oral tablets)
Eletriptan (Relpax 20- and 40-mg oral tablets)
Frovatriptan (Frova 2.5-mg oral tablets)
Ergotamine caffeine (e.g., Cafergot oral tablets; Ergostat sublin-
gual tablets; Wigraine rectal suppository; Medihaler Ergotamine
inhaler; addition of caffeine to oral products improves absorp-
tion; pretreatment with an antiemetic may be required; limit
use to 2 days per week; administer at onset of migraine attack;
contraindicated for patients with prolonged auras [more than
1 hour]).
Dihydroergotamine (D.H.E. 45 IM injection, Migranal 4-mg
nasal spray; pretreatment with an antiemetic is unnecessary;
administer at onset of migraine attack; contraindicated for
patients with prolonged auras [more than 1 hour]).
Ketorolac (Toradol IM injection; useful when triptans or ergot-
amine derivatives are contraindicated or have failed).
Meperidine (IM; useful when standard abortive therapies are
contraindicated or have failed; opioids are the preferred agents
during pregnancy).
Butorphanol (Stadol NS nasal spray; useful when triptans or
ergotamine derivatives are contraindicated or have failed; limit
use to 2 days per week; may cause sedation).
Valproate sodium (Depacon intravenous solution; limited infor-
mation on dose and efficacy; no data available on oral forms of
valproate sodium).
3.c. What pharmacotherapeutic alternatives are available for
prophylaxis of this patients migraine attacks?
Prophylaxis of migraine is recommended when one or more
of the following criteria are met: (1) more than two attacks per
month producing disability lasting at least 3 days per month;
(2) use of abortive medications for more than 2 days per week;
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
71-3
or (3) when acute medications are associated with inadequate
relief or intolerable adverse effects.5 Selection of an agent
CHAPTER 71
depends on the tolerability and comorbid conditions of the
patient. Commonly prescribed prophylactic agents are listed
as follows:
-Blockers are commonly regarded as the treatment of
choice for prophylaxis of migraines. The -blockers without
intrinsic sympathomimetic activity have not been shown to
be effective in migraine prophylaxis. Use -blockers with
caution in patients with asthma, chronic obstructive lung
Migraine Headache
disease, congestive heart failure, diabetes, and Raynauds
disease; they may worsen depression. Example regimens
include:
Metoprolol 50 mg once daily to twice daily initially,
increasing to 100200 mg per day depending on response;
dose the long-acting formulation once daily.
Propranolol 20 mg twice daily initially, increasing to 120
240 mg per day based on response; dose the long-acting
formulation once or twice daily.
Timolol 10 mg twice daily initially, increasing to 2060 mg
per day in divided doses based on response.
Calcium channel blockers are marginally effective; they may
benefit patients with coexisting hypertension.
Verapamil 80 mg two to three times daily initially, increas-
ing as necessary based on response; the long-acting for-
mulation may be given once or twice daily.
Antiepileptic agents:
Valproic acid and divalproex sodium have been shown to
reduce the frequency of migraine headaches by approxi-
mately 50%. Doses as low as 500 mg per day are effective
with the dosing range typically between 500 and 1,500 mg
per day. Adverse events include weight gain, polycystic
ovaries, pancreatitis, tremor, and alopecia.
Gabapentin 300 mg per day initially, with doses titrated
up to a maximum of 800 mg three times daily. In one
double-blind, randomized, placebo-controlled trial, gaba-
pentin 800 mg three times daily reduced the frequency of
migraines by 50% in approximately 30% of patients when
using a modified intention-to-treat analysis. The most fre-
quent adverse effects were somnolence and dizziness. Due
to the equivocal results with gabapentin, it is used rarely
for migraine prevention clinically.
Carbamazepine 200 mg once daily initially. The dose may
be increased to response or adverse effects. There are lim-
ited clinical trials supporting its use in the prophylaxis of
migraines and it is used rarely for migraine prevention
clinically. Carbamazepine may have a role in migraine
associated with trigeminal neuralgia.
Topiramate 100 mg once daily initially. The dose may be
increased to response or adverse effects. In clinical trials,
topiramate 100 mg daily was found to be significantly
better than placebo and comparable to propranolol.
Approximately 50% of patients achieved a 50% reduc-
tion in the frequency of migraines. Two randomized,
double-blind, placebo-controlled trials showed its effi-
cacy in significantly reducing the mean monthly number
of migraines. Adverse events associated with topiramate
include somnolence, paresthesias, weight loss, kidney
stones, abnormal vision, oligohidrosis, and hyperchlor-
emic, nonanion gap metabolic acidosis.
Antidepressants are effective in reducing the frequency of
migraines. They may be particularly useful in patients with
71-4
comorbid depression. Adverse effects include dry mouth,
sedation, and weight gain.
SECTION 6
Amitriptyline 1025 mg once daily initially, increasing as
needed to response or adverse effects
Fluoxetine 20 mg once daily initially; maximum dose 80 mg
once daily
Other agents:
Lisinopril (Zestril) 20 mg once daily. A small randomized,
double-blind, crossover trial showed that lisinopril 20 mg
Neurologic Disorders
daily for 12 weeks decreased the mean number of migraine
days by at least 50%. Adverse effects associated with lisino-
pril are hyperkalemia, cough, and angioedema.5,6
Candesartan (Atacand) 16 mg once daily. A small random-
ized, double-blind, crossover study showed that candesar-
tan reduced the mean number of days with headache and
migraine by at least 50%. Adverse effects include hyper-
kalemia, angioedema, and rash.5,7
Note: Methysergide is no longer available from the manu-
facturer in the United States. This product must now be
compounded if its use is considered necessary.
Menstrual migraines are migraines that occur just before and
several days after menses. Prophylaxis of menstrual migraine is
typically restricted to the highest risk days. Mini-prophylaxis
may be given beginning 2 days prior to the expected start of
migraines and continued for 57 days. Agents that have been
shown to be effective for short-term prophylaxis include the
following8:
Naproxen sodium 550 mg twice daily
Sumatriptan 25 mg twice daily
Naratriptan 1 mg twice daily
Frovatriptan 2.5 mg twice daily on the first day, followed by
2.5 mg daily
Zolmitriptan 2.5 mg twice daily
Optimal Plan
4.a. Considering this patients past successes and failures in treat-
ing her migraine attacks, design an optimal pharmacothera-
peutic plan for aborting her migraine headaches.
Although analgesics and ergotamine are the first choice for
abortive treatment in patients with migraine headaches, this
patient reports a decrease in the efficacy of both analgesics and
ergotamine. Additionally, a trial with naratriptan oral tablets
has also failed to produce significant pain relief. In the event
that one triptan is not effective in producing adequate pain
relief in two of three attacks, it is reasonable to try a different
formulation of the same triptan or an alternative triptan.1,9
Available options with proven efficacy that have not been tried
in this patient include:
Sumatriptan (25-, 50-, and 100-mg oral tablets, 4- and 6-mg
subcutaneous injection, or 5-mg and 20-mg nasal spray)
Almotriptan 6.25- and 12.5-mg oral tablets
Eletriptan 20- and 40-mg oral tablets
Frovatriptan 2.5-mg oral tablet
Rizatriptan 5- and 10-mg oral tablets and orally disintegrat-
ing tablets
Zolmitriptan 2.5- and 5-mg oral tablets, 2.5-mg orally disin-
tegrating tablets, and 5-mg nasal spray
All of the serotonin agonists listed above are effective for
abortive treatment of migraines.1,9 Menstrual migraines
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
appear to respond to these agents as well. As shown above,
some are available in multiple formulations. Subcutaneous
sumatriptan provides the most rapid onset of relief (within 10
minutes). Complete headache relief has been reported in 60
minutes with a 6-mg dose, which is the typical starting dose.
Intranasal administration of a 10-mg dose of sumatriptan
results in relief of headache within 15 minutes. Unfortunately,
this patient does not favor these options and would prefer oral
medications.
The difference in efficacy and tolerability of the remaining trip-
tans may be compared by assessing five different parameters:
(1) proportion of patients with improvement in headache pain
from moderate or severe to mild or no pain at 2 hours post-
dose; (2) proportion of patients pain-free at 2 hours postdose;
(3) recurrence rates of headache pain within 24 hours; (4) pro-
portion of patients with sustained pain relief at 24 hours; and
(5) occurrence of adverse events.1,9
Compared to a dose of sumatriptan 100 mg, rizatriptan 10
mg and eletriptan 80 mg demonstrate higher response rates
at 2 hours, whereas rizatriptan 10 mg, eletriptan 80 mg, and
almotriptan 12.5 mg show higher mean pain-free rates. The
remaining doses and triptans show similar or lower response
rates in the above two parameters.
When compared to a dose of 100 mg of sumatriptan, eletrip-
tan 40- and 80-mg doses show lower recurrence rates, whereas
rizatriptan 5- and 10-mg doses show higher recurrence rates.
A higher proportion of patients who received rizatriptan 10
mg, eletriptan 80 mg, or almotriptan 12.5 mg report sustained
freedom from pain at 24 hours than those who received other
agents.
Almotriptan demonstrates the highest tolerability with fewer
total, central nervous system, and chest adverse events reported
compared to a dose of sumatriptan 100 mg.1,9
After considering the above efficacy and safety parameters,
almotriptan may seem to be the best choice for a trial in this
patient. However, almotriptan undergoes metabolism through
the cytochrome P450 metabolic pathway (3A4), which is
induced (CYP3A) by topiramate (discussed in question 4.b.).4,9
This introduces the potential for a drugdrug interaction
(lower concentrations of almotriptan and decreased efficacy).
Sertraline is also an inhibitor of cytochrome P4503A4, which
presents the potential for another drug interaction.4
Rizatriptan 10 mg may be used as an alternative to almotriptan.
When compared to sumatriptan 100 mg, rizatriptan also dem-
onstrates a higher response rate, a higher proportion of patients
who report pain relief and sustained freedom from pain, and
a similar proportion of adverse events. Rizatriptan undergoes
metabolism through the MAO pathway and may not interact
with topiramate. It is also available as an orally disintegrating
tablet or wafer, which may be better tolerated in someone who
suffers from nausea. Refer to the textbook chapter on headache
disorders for detailed information on these agents.
Extreme caution should always be exercised when administer-
ing rizatriptan (and probably all similar agents with vasocon-
strictive properties) if the prodromal phenomena are severe
(e.g., aphasia or hemiparesis). In these circumstances, waiting
until the aura abates is always prudent.
Triptans are contraindicated in hemiplegic or basilar migraines
and should not be administered in these circumstances.
Triptans are also contraindicated in patients with ischemic
heart disease, coronary artery vasospasm, angina, or other
cardiovascular disease. They should be used with caution in

patients with uncontrolled hypertension or in those who are at
risk for coronary artery disease.
The potential for serotonin syndrome exists in patients exposed
to an MAO-I, SSRI, SNRI, and a triptan concurrently, as these
agents enhance serotonergic neurotransmission. Almotriptan,
rizatriptan, sumatriptan, and zolmitriptan are metabolized by
MAO and would be contraindicated in patients having used
an MAO-I within the past 2 weeks. Patients using an MAO-I
should discontinue 2 weeks prior to initiation of MAO-
metabolized triptans. Refer to question 1.c. for more informa-
tion on the serotonin syndrome.
4.b. Design an optimal pharmacotherapeutic plan for prophy-
laxis of her migraine headaches.
Although -blockers are considered the drugs of choice for pro-
phylactic migraine therapy, this patient was noncompliant with
propranolol after experiencing adverse effects. Furthermore,
this medication may worsen this patients depression.
Valproic acid has proven efficacy, but due to adverse effects of
weight gain, risk of polycystic ovaries, and hyperinsulinemia,
it would be advisable to discontinue this medication. These
risks are a concern in this patient because she has a body mass
index above 25 kg/m2 and a family history of diabetes mellitus.
Additionally, valproic acid has caused a 10-lb weight gain in
this patient, and she has requested an alternative agent.
The remaining available options include the following:
Amitriptyline 1025 mg per day initially, titrating upward as
needed. Amitriptyline is used frequently and has the most con-
sistent evidence supporting its use for migraine prophylaxis. It
is dosed 1025 mg per day initially, with increasing dose based
on response. Amitriptyline displays anticholinergic effects
such as dry mouth and also has side effects of drowsiness and
weight gain.5 This medication is not an appropriate choice for
this patient due to her recent weight gain. Additionally, this
patient has recently started sertraline and use with an SSRI
would increase the risk of serotonin syndrome.
Topiramate 100 mg daily. Of the antiepileptic drugs, topi-
ramate 100 mg daily is the most reasonable choice for this
patient. Adverse events associated with topiramate include
somnolence, paresthesias, weight loss, kidney stones, abnor-
mal vision, oligohidrosis, and hyperchloremic, nonanion gap
metabolic acidosis evidenced by a decreased serum bicarbon-
ate concentration. If topiramate fails to adequately control
the menstrually related migraines in this patient, increasing
the dose of topiramate beginning 2 days prior and continuing
for a total of 7 days may improve headache control.8
Gabapentin 300 mg per day, increasing dose to 800 mg three
times daily. Gabapentin is an anticonvulsant that exhibits
analgesic properties and has demonstrated efficacy in pain
syndromes such as trigeminal and postherpetic neuralgia.
When compared to topiramate, gabapentin has been shown
to be efficacious for the management of headaches in only
one randomized, double-blind study, whereas topiramate
has been shown to be effective in several randomized trials.
Furthermore, weight loss associated with topiramate may
provide an additional benefit for this patient.
Carbamazepine 200 mg once daily, increasing dose based on
response. Carbamazepine has limited efficacy in migraine
prophylaxis.
Verapamil 80 mg three times daily initially, increasing dose
based on response. Verapamil may not be an optimal choice
for this patient considering it may produce adverse events
similar to propranolol.
71-5
Nonpharmacologic therapy such as relaxation training, ther-
mal biofeedback, and electromyographic feedback. These
CHAPTER 71
options may also provide some benefit to this patient.
Thermal biofeedback refers to a patient-controlled, conscious
increase in hand temperature. Electromyographic feedback is
a treatment during which patients learn to control muscle
tension in the face, neck, and shoulders. Both feedback meth-
ods are used in conjunction with relaxation training. Both
techniques are controversial, but they have been included in
the practice parameters published by the American Academy
Migraine Headache
of Neurology as Grade A recommendations.10
This patient should also be referred to health care professionals
specializing in stress management.
Outcome Evaluation
5. Which clinical and/or laboratory parameters should be assessed
regularly to evaluate the therapy for achievement of the desired
therapeutic outcome and to detect or prevent adverse effects?
Abortive therapy:
Efficacy is evaluated by the intensity and duration of headaches
and associated symptoms.
Tolerance and safety are related to the potential side effects of
rizatriptan (Maxalt-MLT) orally disintegrating tablets (a mint-
flavored wafer). Adverse effects reported with rizatriptan (and
the other available triptans) include chest pain; palpitations;
heaviness, pressure, or tightness in the chest, jaw, or neck; flush-
ing; dizziness; drowsiness; and electrocardiogram abnormali-
ties. For patients with a history of chest tightness or pain who
do not have a contraindicated diagnosis (e.g., angina pectoris
or a history of myocardial infarction), a baseline electrocardio-
gram would be prudent to help rule out a cardiac conduction
abnormality. Blood pressure should be monitored closely in
this overweight patient with a family history of hypertension
and risk factors for coronary artery disease.
If another analgesic or analgesic combination was chosen for
this patient, adverse effects include gastrointestinal bleeding
and ulceration, potential for renal dysfunction, as well as the
potential for rebound headaches if these products were over-
used as abortive treatments.
If an ergotamine-containing agent was chosen for this patient,
adverse effects include nausea and vomiting, anorexia, and
limb paresthesias or pain.
Prophylactic therapy:
Efficacy is assessed by the incidence and intensity of headaches
and associated symptoms.
Tolerance and safety are related to the potential side effects of
topiramate such as drowsiness, dizziness, and weakness; kidney
stones; and visual abnormalities. Serum bicarbonate should be
monitored prior to starting therapy and then periodically. If
metabolic acidosis develops and persists, dosage reduction or
gradual cessation of topiramate should be considered.
If a calcium channel blocker was used in this patient, side effects
include constipation, nausea, headache, drowsiness, dizziness,
and edema.
Patient Education
6.a. What information should be provided to the patient regard-
ing migraine triggers?
Common food triggers include alcohol, coffee, caffeine with-
drawal, chocolate, tyramine-containing foods such as cheese
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
71-6
and bananas, and foods containing monosodium glutamate
such as seasoned salt and Chinese food.
SECTION 6
Environmental factors include flickering lights, loud noises,
strong smells, weather changes, and tobacco smoke.
Behavioral factors include lack of sleep, fatigue, skipping meals,
and stress.
Smoking may be a trigger for your migraine headaches and
may be contributing to the increase in headaches you are expe-
riencing. Stopping smoking and avoiding cigarette smoke are
important management tools to prevent headaches.
Neurologic Disorders
6.b. What information should be provided to the patient regard-
ing her new abortive and prophylactic therapies?
General information on the use of triptans for migraine:
Abortive therapy is intended to relieve the effects of an acute
migraine attack but does not reduce the incidence of attacks.
If you become pregnant or intend to become pregnant, notify
your physician so that the risks and benefits of using this drug
during pregnancy can be discussed.
Stop using the drug and contact your physician immediately if
you experience persistent or severe chest pain; wheezing; heart
throbbing; pain or tightness in the throat; rash; lumps; hives; or
swollen eyelids, face, or lips.
Directions for use of rizatriptan orally disintegrating tablets:
You have been prescribed rizatriptan (Maxalt-MLT) 10-mg
orally disintegrating tablets, also called wafers, for the treat-
ment of your migraines.
Do not remove the outer patch until immediately before dosing.
Make sure your hands are dry. Peel open the blister pack.
Place the wafer on your tongue where it will dissolve. Swallow
it with saliva after it has dissolved. You do not have to drink
water with the wafer.
Take only one wafer at the start of the headache. If your head-
ache returns or if the pain only partially decreases, take a second
wafer 2 hours after the initial wafer.
Do not take more than three wafers in a 24-hour period.
Information about topiramate:
You have been prescribed topiramate (Topamax) to prevent
migraine headaches from occurring.
This medicine must be taken every day in order to be effective
in reducing the number of migraines that you have.
To reduce the severity of side effects such as drowsiness, diz-
ziness, and weakness, you will be starting at a low dose and
gradually increasing the dose to an effective level:
During the first week, take 25 mg every evening for 7 days.
Starting the second week, take 25 mg twice daily for 7 days.
Starting the third week, take 25 mg every morning and 50
mg every evening for 7 days.
Starting the fourth week, take 50 mg twice daily and con-
tinue taking this dose.
You may experience the following side effects from topiramate:
tiredness, drowsiness, difficulty concentrating, weight loss, kid-
ney stones, decreased sweating, an increased body temperature,
and visual effects such as blurred vision, changes in vision, or
pain in or around your eyes.
Drink at least eight glasses of water daily to reduce the chance
of kidney stone formation. You may need to drink several extra
glasses of water daily during hot weather, illness, or exercise.
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
To reduce your chances of decreased sweating and increased
body temperature, avoid spending large amounts of time in the
sun. Monitor the amount that you are sweating, avoid becom-
ing overheated in hot weather or during exercise, and keep up
with your fluid intake.
Call your physician immediately if you experience any changes
in your vision or if you experience decreased sweating and an
elevated body temperature.
Information about a potential interaction between triptans
and SSRIs/SNRIs:
In a small number of patients, the administration of rizatrip-
tan with sertraline causes a syndrome known as serotonin
syndrome. Symptoms of this syndrome are shivering, sweat-
ing, diarrhea, restlessness, abnormal foot movements, muscle
twitching, stiffness, agitation, and increased heart rate. If you
experience any of these symptoms, discontinue both medica-
tions and call your doctor or report to the emergency depart-
ment immediately.
M CLINICAL COURSE: ALTERNATIVE THERAPY
While discussing possible changes from her valproic acid therapy,
Ms Miller says that a friend who also has migraines had read about
some herbal remedies used for migraine prevention. She asks
whether any products like that could be used instead of or along
with her prescription medications. Ms Miller is very interested in a
more natural therapy, but only if it could really reduce the num-
ber of her migraines. For questions and answers related to the use
of Butterbur and feverfew for the prevention of migraine headaches,
please see Section 19 of this instructors guide.
Follow-Up Question
1. Describe how a headache diary could help the treatment of
this patients migraine headaches. (See Fig. 71-2 for headache
diary).
Headache diaries or activity logs may be used to refine headache
treatments. A headache diary is simply a document that accu-
rately describes the headache profile and the medications taken
for an attack. Each entry into the diary should include the date
of attack, duration of attack, presence or absence of an aura,
description of aura (if present), intensity of attack, description
of pain, associated symptoms, precipitating factors (e.g., exer-
cise, food), nondrug therapy instituted and its effect, abortive
therapy required and its effect, side effects of medications, and
overall impact of each headache on lifestyle or daily activities.
Additional information to include in the diary is the date and
time of daily prophylactic medication administration.
The information gained in a headache diary can assist in iden-
tifying trigger factors, including the overuse of abortive agents,
and in assessing current drug efficacy and tolerance, as well as
acting as a reminder for the patient to take the prophylactic
medications as prescribed. A sample headache diary is included
in Fig. 71-2. Diaries should accompany the patient each time
they visit the physicians office.
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receptor agonists (triptans), selective serotonin reuptake inhibitors
(SSRIs) or selective serotonin/norepinephrine reuptake inhibitors
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at: http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm
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Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
71-7
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CHAPTER 71
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