Chapter

54 Headache: Migraine and

Tension-Type

MIGRAINE HEADACHE
• Migraine, a common, recurrent, primary headache of moderate to severe intensity,
interferes with normal functioning and is associated with gastrointestinal (GI), neu-
rologic, and autonomic symptoms. In migraine with aura, focal neurologic symptoms
precede or accompany the attack.
PATHOPHYSIOLOGY
• Activation of trigeminal sensory nerves triggers the release of vasoactive neuropep-
tides, including calcitonin gene-related peptide, neurokinin A, and substance P from
perivascular axons. Vasodilation of dural blood vessels may occur with extravasation
of dural plasma resulting in inflammation.
• Twin studies suggest 50% heritability of migraine, with a multifactorial polygenic
basis. Migraine triggers may be modulators of the genetic set point that predisposes
to migraine headache.
• Specific populations of serotonin (5-HT) receptors appear to be involved in the
pathophysiology and treatment of migraine headache. Ergot alkaloids and triptan
derivatives are agonists of vascular and neuronal 5-HT1 receptors, resulting in vaso-
constriction and inhibition of vasoactive neuropeptide release.
CLINICAL PRESENTATION AND DIAGNOSIS
• Migraine headache is characterized by recurring episodes of throbbing head pain,
frequently unilateral.
• Approximately 12% to 79% of migraineurs have premonitory symptoms (not to
be confused with aura) in the hours or days before headache onset. Neurologic
symptoms (phonophobia, photophobia, hyperosmia, and difficulty concentrating)
are most common, but psychological (anxiety, depression, euphoria, irritability,
drowsiness, hyperactivity, and restlessness), autonomic (eg, polyuria, diarrhea, and
constipation), and constitutional (eg, stiff neck, yawning, thirst, food cravings, and
anorexia) symptoms may also occur.
• A migraine aura is experienced by approximately 25% of migraineurs. Aura evolves
over 5 to 20 minutes and lasts less than 60 minutes. Headache usually occurs within
60 minutes of the end of the aura. Visual auras can include both positive features (eg,
scintillations, photopsia, teichopsia, and fortification spectrum) and negative features
(eg, scotoma and hemianopsia). Sensory and motor symptoms such as paresthesias
or numbness of the arms and face, dysphasia or aphasia, weakness, and hemiparesis
may also occur.
• Migraine headache may occur at any time but usually occurs in the early morning.
Pain is usually gradual in onset, peaking in intensity over minutes to hours and last-
ing 4 to 72 hours. Pain is typically in the frontotemporal region and is moderate to
severe. Headache is usually unilateral and throbbing with GI symptoms (eg, nausea
and vomiting) almost invariably accompanying the headache. Other systemic symp-
toms include anorexia, constipation, diarrhea, abdominal cramps, nasal stuffiness,
blurred vision, diaphoresis, facial pallor, and localized facial, scalp, or periorbital
edema. Sensory hyperacuity (photophobia, phonophobia, or osmophobia) is fre-
quent. Many patients seek a dark, quiet place.
• Once the headache pain wanes, a resolution phase characterized by exhaustion, mal-
aise, and irritability ensues.
• A comprehensive headache history is essential and includes age at onset; frequency,
timing, and duration of attacks; possible triggers; ameliorating factors; description
and characteristics of symptoms; associated signs and symptoms; treatment history;
and family and social history.

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• Neuroimaging should be considered in patients with unexplained abnormal neuro-

logic examination or atypical headache history.
• Onset of migraine headaches after age 50 suggests an organic etiology, such as a mass
lesion, cerebrovascular disease, or temporal arteritis.
TREATMENT
• Goals of Treatment: The goal is to achieve consistent, rapid headache relief with
minimal adverse effects and symptom recurrence, and minimal disability and emo-
tional distress, thereby enabling the patient to resume normal daily activities. Ideally,
patients should be able to manage their headaches effectively without emergency
department or physician office visits.
• Limit use of acute migraine therapies to fewer than 10 days per month to avoid devel-
opment of medication-misuse headache.
Nonpharmacologic Treatment
• Apply ice to the head and recommend periods of rest or sleep, usually in a dark, quiet
environment.
• Identify and avoid triggers of migraine attacks (Table 54–1).
• Behavioral interventions (relaxation therapy, biofeedback, and
cognitive therapy)
may help patients who prefer nondrug therapy or when drug therapy is ineffective
or not tolerated.

TABLE 54–1 Commonly Reported Triggers of Migraine

Food triggers
Alcohol
Caffeine/caffeine withdrawal
Chocolate
Fermented and pickled foods
Monosodium glutamate (e.g., in Chinese food, seasoned salt, and instant foods)
Nitrate-containing foods (e.g., processed meats)
Saccharin/aspartame (e.g., diet foods or diet sodas)
Tyramine-containing foods
Environmental triggers
Glare or flickering lights
High altitude
Loud noises
Strong smells and fumes
Tobacco smoke
Weather changes
Behavioral–physiologic triggers
Excess or insufficient sleep
Fatigue
Menstruation, menopause
Sexual activity
Skipped meals
Strenuous physical activity (e.g., prolonged overexertion)
Stress or post stress

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 Headache: Migraine and Tension-Type   |   CHAPTER 54

Pharmacologic Treatment of Acute Migraine

• Administer acute migraine therapies (Table 54–2) at the onset of migraine. (See
algorithm in Fig. 54–1.)
• Pretreatment with an antiemetic (eg, metoclopramide, chlorpromazine, or pro-
chlorperazine) 15 to 30 minutes before oral or nonoral migraine treatments (rectal
suppositories, nasal spray, or injections) may be advisable when nausea and vomiting
are severe. In addition to its antiemetic effects, metoclopramide helps reverse gastro-
paresis and enhances absorption of oral medications.
• Frequent or excessive use of acute migraine medications can result in increasing
headache frequency and drug consumption known as medication-overuse headache.
This occurs commonly with overuse of simple or combination analgesics, opiates,
ergotamine tartrate, and triptans. Limit use of acute migraine therapies to 2 or 3
days per week.
ANALGESICS AND NONSTEROIDAL ANTIINFLAMMATORY DRUGS
• Simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are first-
line treatments for mild to moderate migraine attacks; some severe attacks are also
responsive. Aspirin, diclofenac, ibuprofen, ketorolac, naproxen sodium, tolfen-
amic acid, and the combination of acetaminophen plus aspirin and caffeine are
effective.
• NSAIDs appear to prevent neurogenically mediated inflammation in the trigemino-
vascular system by inhibiting prostaglandin synthesis.
• In general, NSAIDs with a long half-life are preferred, as less frequent dosing is
needed. Rectal suppositories and intramuscular (IM) ketorolac are options for
patients with severe nausea and vomiting.
• The combination of acetaminophen, aspirin, and caffeine is approved in the United
States for relieving migraine pain.
• Aspirin and acetaminophen are also available by prescription in combination with
a short-acting barbiturate (butalbital). No randomized, placebo-controlled studies
support the efficacy of butalbital-containing formulations for migraine.
• Midrin, a proprietary combination of acetaminophen, isometheptene mucate (a
sympathomimetic amine), and dichloralphenazone (a chloral hydrate derivative),
may be an alternative for patients with mild to moderate migraine attacks.
ERGOT ALKALOIDS AND DERIVATIVES
• Ergot alkaloids are useful for moderate to severe migraine attacks. They are non­
selective 5HT1 receptor agonists that constrict intracranial blood vessels and inhibit
the development of neurogenic inflammation in the trigeminovascular system. Venous
and arterial constriction occurs. They also have activity at dopaminergic receptors.
• Ergotamine tartrate is available for oral, sublingual, and rectal administration. Oral
and rectal preparations contain caffeine to enhance absorption and potentiate anal-
gesia. Titrate to an effective dose that is not nauseating.
• Dihydroergotamine (DHE) is available for intranasal and parenteral (IM, IV, or
subcutaneous [SC]) administration. Patients can self-administer IM or SC DHE.
• Nausea and vomiting are common with ergotamine derivatives, so consider anti-
emetic pretreatment. Other common side effects include abdominal pain, weakness,
fatigue, paresthesias, muscle pain, diarrhea, and chest tightness. Symptoms of severe
peripheral ischemia (ergotism) include cold, numb, painful extremities; continuous
paresthesias; diminished peripheral pulses; and claudication. Gangrenous extremi-
ties, myocardial infarction (MI), hepatic necrosis, and bowel and brain ischemia have
occurred rarely with ergotamine. Do not use ergotamine derivatives and triptans
within 24 hours of each other.
• Contraindications to use of ergot derivatives include renal and hepatic failure; coro-
nary, cerebral, or peripheral vascular disease; uncontrolled hypertension; sepsis; and
women who are pregnant or nursing.
• DHE does not appear to cause rebound headache, but dosage restrictions for ergota-
mine tartrate should be strictly observed to prevent this complication.
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SECTION 9   |   Neurologic Disorders

TABLE 54–2 Dosing of Acute Migraine Therapiesa
Drug Dose Usual Range/Comments
Analgesics
Acetaminophen (Tylenol) 1,000 mg at onset; repeat every 4–6 hours as needed Maximum daily dose is 4 g
Acetaminophen 250 mg/aspirin 250 mg/ 2 tablets at onset and every 6 hours Available as nonprescription medication as Excedrin Migraine
caffeine 65 mg (Excedrin Migraine)
Nonsteroidal Antiinflammatory Drugs
Aspirin 500–1,000 mg every 4–6 hours Maximum daily dose is 4 g
Ibuprofen (Motrin) 200–800 mg every 6 hours Avoid doses >2.4 g/day
Naproxen sodium (Aleve, Anaprox) 550–825 mg at onset; can repeat 220 mg in 3–4 hours Avoid doses >1.375 g/day
Diclofenac (Cataflam, Voltaren) 50–100 mg at onset; can repeat 50 mg in 8 hours Avoid doses >150 mg/day
Ergotamine Tartrate
Oral tablet (1 mg) with caffeine 100 mg 2 mg at onset; then 1–2 mg every 30 minutes as needed Maximum dose is 6 mg/day or 10 mg/wk; consider
(Cafergot) pretreatment with an antiemetic
Sublingual tablet (2 mg) (Ergomar)
Rectal suppository (2 mg) with caffeine Insert 0.5 to 1 suppository at onset; repeat after 1 hour as Maximum dose is 4 mg/day or 10 mg/wk; consider
100 mg (Cafergot, Migergot) needed pretreatment with an antiemetic
 Dihydroergotamine
Injection 1 mg/mL (D.H.E. 45) 0.25–1 mg at onset IM, IV, or subcutaneous; repeat every Maximum dose is 3 mg/day or 6 mg/wk
hour as needed
Nasal spray 4 mg/mL (Migranal) One spray (0.5 mg) in each nostril at onset; repeat Maximum dose is 3 mg/day; prime sprayer four times before
sequence 15 minutes later (total dose is 2 mg or using; do not tilt head back or inhale through nose while
four sprays) spraying; discard open ampules after 8 hours
Serotonin Agonists (Triptans)
Sumatriptan (Imitrex)
Injection 6 mg subcutaneous at onset; can repeat after 1 hour if Maximum daily dose is 12 mg

Headache: Migraine and Tension-Type   |   CHAPTER 54

needed
Oral tablets 25, 50, 85, or 100 mg at onset; can repeat after 2 hours if Optimal dose is 50–100 mg; maximum daily dose is 200 mg;
needed combination product with naproxen, 85/500 mg
Nasal spray 5, 10, or 20 mg at onset; can repeat after 2 hours if needed Optimal dose is 20 mg; maximum daily dose is 40 mg;
single-dose device delivering 5 or 20 mg; administer one
spray in one nostril
Zolmitriptan (Zomig, Zomig-ZMT)
Oral tablets 2.5 or 5 mg at onset as regular or orally disintegrating Optimal dose is 2.5 mg; maximum dose is 10 mg/day
tablet; can repeat after 2 hours if needed
Do not divide ODT dosage form
Nasal spray 5 mg (one spray) at onset; can repeat after 2 hours Maximum daily dose is 10 mg/day
if needed
Naratriptan (Amerge) 1 or 2.5 mg at onset; can repeat after 4 hours if needed Optimal dose is 2.5 mg; maximum daily dose is 5 mg
(continued )
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SECTION 9   |   Neurologic Disorders

TABLE 54–2 Dosing of Acute Migraine Therapiesa (Continued )
Drug Dose Usual Range/Comments
Rizatriptan (Maxalt, Maxalt-MLT) 5 or 10 mg at onset as regular or orally disintegrating tablet; Optimal dose is 10 mg; maximum daily dose is 30 mg;
can repeat after 2 hours if needed onset of effect is similar with standard and orally
disintegrating tablets; use 5-mg dose (15 mg/day maximum)
in patients receiving propranolol
Almotriptan (Axert) 6.25 or 12.5 mg at onset; can repeat after 2 hours if needed Optimal dose is 12.5 mg; maximum daily dose is 25 mg
Frovatriptan (Frova) 2.5 or 5 mg at onset; can repeat in 2 hours if needed Optimal dose 2.5–5 mg; maximum daily dose is 7.5 mg
(three tablets)
Eletriptan (Relpax) 20 or 40 mg at onset; can repeat after 2 hours if needed Maximum single dose is 40 mg; maximum daily dose is 80 mg
Miscellaneous
Metoclopramide (Reglan) 10 mg IV at onset Useful for acute relief in the office or emergency department
setting
Prochlorperazine (Compazine) 10 mg IV or IM at onset Useful for acute relief in the office or emergency department
setting

ODT, orally disintegrating tablet.

a
Limit use of symptomatic medications to fewer than 10 days/mo when possible to avoid medication-misuse headache.
 Headache: Migraine and Tension-Type   |   CHAPTER 54

Diagnosis of migraine

Patient education regarding a general wellness

program and avoidance of trigger factors

Consider
Assess headache severity and degree of
prophylactic
associated disability
pharmacotherapy

If associated with severe nausea or vomiting,

pretreat with antiemetic: consider use of
suppository, parenteral or intranasal formulation

Mild to moderate symptoms Severe symptoms

Simple analgesic: acetaminophen

NSAIDs: aspirin, ibuprofen, naproxen
Inadequate response
Combination analgesics:
acetaminophen/aspirin/caffeine
Inadequate response

Triptans Dihydroergotamine or
ergotamine tartrate

Inadequate response
Combinations, rescue therapy

FIGURE 54–1. Treatment algorithm for migraine headaches.

SEROTONIN RECEPTOR AGONISTS (TRIPTANS)

• The triptans (Table 54–3) are appropriate first-line therapies for patients with mild
to severe migraine or as rescue therapy when nonspecific medications are ineffective.
• They are selective agonists of the 5HT1B and 5HT1D receptors. Relief of migraine
headache results from (1) normalization of dilated intracranial arteries, (2) inhibition
of vasoactive peptide release, and (3) inhibition of transmission through second-
order neurons ascending to the thalamus.
• Sumatriptan SC injection is packaged as an autoinjector device for self-administra-
tion. Compared with the oral formulation, SC administration offers enhanced effi-
cacy and more rapid onset of action. Intranasal sumatriptan also has a faster onset of
effect than the oral formulation and produces similar rates of response.
• Second-generation triptans (all except sumatriptan) have higher oral bioavailability
and longer half-lives than oral sumatriptan, which could theoretically reduce head-
ache recurrence. However, comparative clinical trials are necessary to determine their
relative efficacy.
• Pharmacokinetic characteristics of the triptans are shown in Table 54–3.
• Lack of response to one triptan does not preclude effective therapy with another
triptan.
• Side effects of triptans include paresthesias, fatigue, dizziness, flushing, warm sensa-
tions, and somnolence. Minor injection site reactions are reported with SC use, and
taste perversion and nasal discomfort may occur with intranasal administration.
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TABLE 54–3 Pharmacokinetic Characteristics of Triptans

Time to
Maximal
Half-Life Concentration Bioavailability
Drug (Hours) (tmax) (%) Elimination
Almotriptan 3–4 1.4–3.8 hours 80 MAO-A, CYP3A4, CYP2D6
Eletriptan 4–5 1–2 hours 50 CYP3A4
Frovatriptan 25 2–4 hours 24–30 Mostly unchanged,
CYP1A2
Naratriptan 5–6 2–3 hours 63–74 Largely unchanged,
CYP450 (various
isoenzymes)
Rizatriptan 2–3 45 MAO-A
Oral tablets 1–1.2 hours
Disintegrating 1.6–2.5 hours
Sumatriptan 2 MAO-A
SC injection 12–15 minutes 97
Oral tablets 2.5 hours 14
Nasal spray 1–2.5 hours 17
Zolmitriptan 3 40–48 CYP1A2, MAO-A
Oral 2 hours
Disintegrating 3.3 hours
Nasal 4 hours

CYP, cytochrome P450; MAO-A, monoamine oxidase type A.

Up to 25% of patients report chest tightness; pressure; heaviness; or pain in the chest,
neck, or throat. The mechanism of these symptoms is unknown, but a cardiac source
is unlikely in most patients. Isolated cases of MI and coronary vasospasm with isch-
emia have been reported.
• Contraindications include ischemic heart disease, uncontrolled hypertension, cere-
brovascular disease, hemiplegic and basilar migraine, and pregnancy. Do not give
triptans within 24 hours of ergotamine derivative administration or within 2 weeks of
therapy with monoamine oxidase inhibitors. Concomitant use of triptans with selec-
tive serotonin reuptake inhibitors or serotonin–norepinephrine reuptake inhibitors
can cause serotonin syndrome, a potentially life-threatening condition.
• Use triptans cautiously in patients at risk for unrecognized coronary artery disease.
Do a cardiovascular assessment before giving triptans to postmenopausal women,
men over 40 years of age, and patients with uncontrolled risk factors, and administer
the first dose under medical supervision.
OPIOIDS
• Reserve opioids and derivatives (eg, meperidine, butorphanol, oxycodone, and
hydromorphone) for patients with moderate to severe infrequent headaches in
whom conventional therapies are contraindicated or as rescue medication after fail-
ure to respond to conventional therapies. Closely supervise opioid therapy.
Pharmacologic Prophylaxis of Migraine
• Prophylactic therapies (Table 54–4) are administered daily to reduce the frequency,
severity, and duration of attacks, and to increase responsiveness to acute therapies.
(See algorithm in Fig. 54–2.)
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 TABLE 54–4 Dosing of Prophylactic Migraine Therapies
Drug Initial Dose Usual Range Comments
β-Adrenergic Antagonists
Atenolola (Tenormin) 50 mg/day 50–200 mg/day
Metoprololb (Toprol, Toprol XL) 100 mg/day in divided doses 100–200 mg/day in divided doses Dose short-acting four times a day and long-acting two
times a day; available as extended release
Nadolola (Corgard) 40–80 mg/day 80–240 mg/day
Propranololb (Inderal, Inderal LA) 40 mg/day in divided doses 40–160 mg/day in divided doses Dose short-acting two to three times a day and
long-acting one to two times a day; available as

Headache: Migraine and Tension-Type   |   CHAPTER 54

extended release
Timololb (Blocadren) 20 mg/day in divided doses 20–60 mg/day in divided doses
Antidepressants
Amitriptylinea (Elavil) 10 mg at bedtime 20–50 mg at bedtime
Venlafaxinea (Effexor, Effexor XR) 37.5 mg/day 75–150 mg/day Available as extended release; increase dose after 1 week
Anticonvulsants
Topiramateb (Topamax) 25 mg/day 50–200 mg/day in divided doses As effective as amitriptyline, propranolol, or valproate;
increase by 25 mg/wk
Valproic acid/divalproex sodiumb 250–500 mg/day in divided doses, 500–1,500 mg/day in divided Monitor levels if compliance is an issue
(Depakene, Depakote, Depakote ER) or daily for extended release doses, or daily for extended
release
Nonsteroidal Antiinflammatory Drugs
Ibuprofena (Motrin) 400–1,200 mg/day in divided doses Same as initial dose Use intermittently, such as for menstrual migraine prevention;
daily or prolonged use may lead to medication-overuse
headache and is limited by potential toxicity
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TABLE 54–4 Dosing of Prophylactic Migraine Therapies (Continued )
Drug Initial Dose Usual Range Comments
Ketoprofena (Orudis) 150 mg/day in divided doses Same as initial dose
Naproxen sodiuma (Aleve, Anaprox) 550–1,100 mg/day in divided doses Same as initial dose
Serotonin Agonists (Triptans)
Frovatriptanb (Frova) 2.5 or 5 mg/day in divided doses Same as initial dose Taken in the perimenstrual period to prevent menstrual
migraine
Naratriptana (Amerge) 2 mg/day in divided doses Same as initial dose
Zolmitriptana (Zomig) 5–7.5 mg/day in divided doses Same as initial dose
Miscellaneous
Histaminea (Histatrol) 1–10 ng two times per week Same as initial dose May cause transient itching and burning at injection site
Magnesiuma 400 mg/day 800 mg/day in divided doses May be more helpful in migraine with aura and menstrual
migraine
MIG-99a (feverfew) 10–100 mg/day in divided doses Same as initial dose Withdrawal may be associated with increased headaches
Petasitesb 100–150 mg/day in divided doses 150 mg/day in divided doses Use only commercial preparations; plant is carcinogenic
Riboflavina 400 mg/day in divided doses 400 mg/day in divided doses Benefit only after 3 months
a
Level B—probably effective (one Class I or two Class II studies).
b
Level A—established efficacy (>2 Class I studies).
 Patient meets criteria for
prophylactic
pharmacotherapy

Headaches recur in Healthy or comorbid Comorbid depression Comorbid seizure disorder Other agents

Headache: Migraine and Tension-Type   |   CHAPTER 54

a predictable pattern hypertension or angina or insomnia or bipolar illness ineffective
(eg, menstrual
migraine)

Ineffective Ineffective Ineffective Consider combination

NSAID or triptan at β-Adrenergic antagonist Tricyclic antidepressant Anticonvulsant therapy; consult
the (verapamil if β-adrenergic headache specialist
time of vulnerability antagonist contraindicated Ineffective
or ineffective)
β-Adrenergic antagonist
(verapamil if β-adrenergic Ineffective
antagonist contraindicated
or ineffective)

FIGURE 54–2. Treatment algorithm for prophylactic management of migraine headaches. (NSAID, nonsteroidal anti-inflammatory drug.)
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• Consider prophylaxis in the setting of recurring migraines that produce significant

disability; frequent attacks requiring symptomatic medication more than twice per
week; symptomatic therapies that are ineffective, contraindicated, or produce serious
side effects; uncommon migraine variants that cause profound disruption or risk of
neurologic injury; and patient preference to limit the number of attacks.
• Preventive therapy may also be given intermittently when headaches recur in a pre-
dictable pattern (eg, exercise-induced or menstrual migraine).
• Because efficacy of various prophylactic agents appears to be similar, drug selection
is based on side effect profiles and comorbid conditions. Response to an agent is
unpredictable, and a 2- to 3-month trial is necessary to judge efficacy.
• Only propranolol, timolol, divalproex sodium, and topiramate are Food and Drug
Administration (FDA) approved for migraine prevention.
• Initiate prophylaxis with low doses, and advance slowly until a therapeutic effect is
achieved or side effects become intolerable.
• Continue prophylaxis for at least 6 to 12 months after headache frequency and sever-
ity have diminished, and then gradual tapering or discontinuation may be reasonable.

β-ADRENERGIC ANTAGONISTS
• Propranolol, timolol, and metoprolol reduce the frequency of migraine attacks by
50% in more than 50% of patients. Atenolol and nadolol are probably also effective.
β-Blockers with intrinsic sympathomimetic activity are ineffective.
• Bronchoconstrictive and hyperglycemic effects can be minimized with β1-selective
β-blockers.
• Side effects include drowsiness, fatigue, sleep disturbances, vivid dreams, memory
disturbance, depression, sexual dysfunction, bradycardia, and hypotension.
• Use with caution in patients with heart failure, peripheral vascular disease, atrioven-
tricular conduction disturbances, asthma, depression, and diabetes.

ANTIDEPRESSANTS
• The tricyclic antidepressants (TCA) amitriptyline and venlafaxine are probably
effective for migraine prophylaxis. There are insufficient data to support or refute the
efficacy of other antidepressants.
• Their beneficial effects in migraine prophylaxis are independent of antidepres-
sant activity and may be related to downregulation of central 5HT2 and adrenergic
receptors.
• TCAs are usually well tolerated at the doses used for migraine prophylaxis, but anti-
cholinergic effects may limit use, especially in elderly patients or those with benign
prostatic hyperplasia or glaucoma. Evening doses are preferred because of sedation.
Increased appetite and weight gain can occur. Orthostatic hypotension and slowed
atrioventricular conduction are occasionally reported.
• Phenelzine has been used for refractory headache, but its complex side-effect profile
and dietary and medication restrictions limit its use.

ANTICONVULSANTS
• Valproic acid, divalproex sodium (a 1:1 molar combination of valproate sodium
and valproic acid), and topiramate can reduce the frequency, severity, and duration
of headaches.
• Side effects of valproic acid and divalproex sodium include nausea (less common
with divalproex sodium and gradual dosing titration), tremor, somnolence, weight
gain, hair loss, and hepatotoxicity (the risk of hepatotoxicity appears to be low in
patients older than 10 years on monotherapy). The extended-release formulation of
divalproex sodium is administered once daily and is better tolerated than the enteric-
coated formulation. Valproate is contraindicated in pregnancy and patients with a
history of pancreatitis or chronic liver disease.
• Fifty percent of patients respond to topiramate. Paresthesias (~50% of patients) and
weight loss (9%–12% of patients) are common. Other side effects include fatigue,
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 Headache: Migraine and Tension-Type   |   CHAPTER 54

anorexia, diarrhea, difficulty with memory, language problems, taste perversions, and
nausea. Kidney stones, acute myopia, acute angle-closure glaucoma, and oligohidro-
sis have been infrequently reported.

NONSTEROIDAL ANTIINFLAMMATORY DRUGS

• Nonsteroidal anti-inflammatory drugs (NSAIDs) are modestly effective for reduc-
ing the frequency, severity, and duration of migraine attacks, but potential GI and
renal toxicity limit daily or prolonged use.
• They may be used intermittently to prevent headaches that recur in a predictable pat-
tern (eg, menstrual migraine). Treatment should be initiated 1 or 2 days before the
time of headache vulnerability and continued until vulnerability is passed.
• For migraine prevention, evidence for efficacy is strongest for naproxen and weakest
for aspirin.

OTHER DRUGS
• Verapamil has been widely used, but evidence for efficacy is inadequate.
• Frovatriptan is effective for prophylaxis of menstrual migraine, and naratriptan and
zolmitriptan are probably effective.
• Other medications that may be effective include Petasites, riboflavin (vitamin B2),
extract of feverfew, subcutaneous histamine, lisinopril, candesartan, clonidine,
guanfacine, and coenzyme Q10, but additional research is needed to confirm
efficacy.

TENSION-TYPE HEADACHE
• Tension-typeheadache, the most common type of primary headache, is more
common in women than men. Pain is usually mild to moderate and nonpulsatile.
Episodic headaches may become chronic in some patients.

PATHOPHYSIOLOGY
• Pain is thought to originate from myofascial factors and peripheral sensitization of
nociceptors. Central mechanisms are also involved. Mental stress, nonphysiologic
motor stress, a local myofascial release of irritants, or a combination of these may be
the initiating stimulus.

CLINICAL PRESENTATION
• Premonitory symptoms and aura are absent, and pain is usually mild to moderate,
bilateral, nonpulsatile, and in the frontal and temporal areas, but occipital and pari-
etal areas can also be affected.
• Mild photophobia or phonophobia may occur. Pericranial or cervical muscles may
have tender spots or localized nodules in some patients.

TREATMENT
• Nonpharmacologic therapies include reassurance and counseling, stress manage-
ment, relaxation training, and biofeedback. Physical therapeutic options (eg, heat or
cold packs, ultrasound, electrical nerve stimulation, massage, acupuncture, trigger
point injections, and occipital nerve blocks) have performed inconsistently.
• Simple analgesics (alone or in combination with caffeine) and NSAIDs are
the mainstay of acute therapy. Acetaminophen, aspirin, diclofenac, ibuprofen,
naproxen, ketoprofen, and ketorolac are effective.
• High-dose NSAIDs and the combination of aspirin or acetaminophen with butal-
bital, or rarely, codeine are effective options. Avoid the use of butalbital and codeine
combinations when possible.
• Give acute medication for episodic headache no more often than 3 days (butalbital-
containing), 9 days (combination analgesics), or 15 days (NSAIDs) per month to
prevent the development of chronic tension-type headache.
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SECTION 9   |   Neurologic Disorders

• There is no evidence to support the efficacy of muscle relaxants.

• Consider preventive treatment if headache frequency is more than two per week,
duration is longer than 3 to 4 hours, or severity results in medication overuse or
substantial disability.
• The TCAs are used most often for prophylaxis of tension headache, but venlafaxine,
mirtazapine, gabapentin, and topiramate may also be effective.

EVALUATION OF THERAPEUTIC OUTCOMES

• Monitor for frequency, intensity, and duration of headaches and for any change in
the headache pattern. Encourage patients to keep a headache diary to document
frequency, duration, and severity of headaches, headache response, and potential
triggers of migraine headaches.
• Monitor patients taking abortive therapy for frequency of use of prescription and
nonprescription medications and for side effects.
• Document patterns of abortive medication used to establish the need for prophy-
lactic therapy. Monitor prophylactic therapies closely for adverse reactions, abortive
therapy needs, adequate dosing, and compliance.

See Chapter 45, Headache Disorders, authored by Deborah S. Minor and Marion R.
Wofford, for a more detailed discussion of this topic.
556