HEADACHE: MANAGEMENT GUIDELINES
From Pain Management in Women Over the Lifecycle, presented by the University of California, San Diego, School
of Medicine and the Diana Padelford Binkley Foundation
| HEADACHE: STEPWISE EVALUATION AND TREATMENT— Christy M. Jackson, MD, Associate Clinical Professor,
Department of Neurosciences and Director, Headache Clinic, University of California, San Diego, School of Medicine
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| Migraine: occurs most often in women 30 to 40 yr of age; pediatric patients with migraine—can present without classic
symptoms, eg, young women with symptoms of fatigue, nausea, pallor, and fainting; mother can provide important data on
medical history; women may—present with focal symptoms that lead to misdiagnosis as stroke; prefer to describe migraine
as “sick headache” or headache related to weather changes, hunger, or consumption of red wine; additional concerns—
rate of misdiagnosis 59% among women with clinical criteria for migraine (rate higher among men); diagnostic yield not
improved by increased use of over-the-counter (OTC) medications
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| Level 1 headache: moderate; intermittent; responds to OTC medications; often not viewed as migraine; migraine as sinus
headache—number one misdiagnosis; vasoconstrictive agents help relieve migraine; although most migraineurs have nasal
congestion and sensation of sinus stuffiness, true fever and discharge absent (determine whether patient requires antibiotic
therapy or responds well to pseudoephedrine [Sudafed]); analgesic rebound—associated with overuse of
pseudoephedrine; combines with migraine
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| Organic disease: found in 2% of patients; ordinary computed tomography (CT) preferred for evaluation (CT with contrast
and lumbar puncture rules out meningitis or mass effect); neurologic examination—confirms diagnosis made from history;
mandated by focal neurologic findings; patient presenting during migraine or postictal period—may have focal
disease with unilateral hyperreflexia; signs (eg, Babinski sign, papilledema, visual-field cut) absent; reevaluate at 24 to
48 hr
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| Primary disorders to rule out
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 | Episodic tension-type headache: common misdiagnosis in patients with mild migraine; pain—bilateral and “squeezing”
initially; not aggravated by routine physical activity; no nausea, vomiting, light or sound sensitivity, or vertigo;
points—patients can transition from tension-type headache to migraine; wider range of treatment options available for
migraine; appropriate medical therapy for tension-type headache corrects craniocervical muscle imbalance and facilitates
physical therapy, not “quick fix”; if vascular headache diagnosed initially, patient’s response to therapy faster
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| Chiari type I malformation: detected by sagittal magnetic resonance imaging (MRI); consider in adult with suspicious
history (eg, tension-type headaches since childhood); ≤3 mm descent often asymptomatic; sudden activity can cause
further descent and trigger symptoms
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| Cluster headache: more common in men; some women have migraine with cluster-like features (treat both types of headache);
pain—severe, unilateral, penetrating, and supraorbital; does not switch sides; accompanied by miosis, ptosis, and
lacrimation; lasts from 15 to 180 min; often occurs at same time each day; can awaken patient; patients—experience first
headache episode at 20 to 30 yr of age; restless; demonstrate characteristic phenotype of ruddy complexion, hazel colored
eyes, and light colored hair; exhausted after episode; tend to develop ulcers and be heavy smokers; patient without primary
headache disorder—>40 yr of age; has unusual periorbital pain, lacrimation, and rhinorrhea; requires MRI to detect
organic pathology; CT images unsatisfactory
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| Trigeminal neuralgia: may have atypical features; often confused with cluster headache; more common among women; differs
from cluster headache and migraine in age at onset and characteristics of pain; shares with migraine common mediation
through trigeminal nerve; can be triggered by traumatic injection into trigeminal nerve roots (difficult to treat); pain—lan-
cinating; debilitating; does not burn; responds to carbamazepine and antiepileptic medications that prevent migraine
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| Without aura: office diagnosis requires 2 of—unilateral (may be bilateral) pulsatile pain (may not be pulsatile initially),
nausea, and photophobia; International Headache Society—requires ≥5 episodes for diagnosis of migraine
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| With aura: question every woman with headache about prodromal aura (many patients focus on pain and never mention
aura); manifestations of aura—“flickering finger” sign (may occur without headache); scintillating scotoma; fortification
spectra; sensory paresthesias; bottom line—because aura can include any neurologic function of cortex, migraineurs
can experience vertigo, aphasia, hemiparesis, and sensory and visual changes
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| Diagnosis: migraine with aura has genetic basis; pain—bilateral in tension headache; pulsatile in migraine headache; nonpulsatile
in cluster headache; familial hemiplegic migraine—may be present in child with alternating hemiplegia; history
reveals familial pattern; headache history—important; questionnaire simplifies process; preceding and associated
symptoms help identify migraine; migraine triggers—changes in barometric pressure, eg, “sinus headache” combined
with allergy but no infection; menstrual cycle
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| Relationship between migraine and hormonal cycle: migraine—starts at menarche; triggered by fluctuating hormone
levels; oral contraceptives (OCs)—may help treat migraine in anovulatory woman with irregular hormonal cycles;
administer lowest estrogen level possible; pregnancy—migraines occur during first trimester, ie, severity worsens as
estrogen increases; no migraines occur during second and third trimesters when estrogen levels stabilize
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| Acephalgic migraine: replaces standard migraine during perimenopausal period, ie, some women who experienced migraine
with aura during 20s and 30s now see bright white light lasting 15 min without pain; patients—experiencing
changes in headache and visual phenomena require imaging of occipital cortex to rule out organic disease; may respond
to estrogen patch
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| Points on evaluation: women in perimenopausal age range who experience changes in headache characteristics—
ask about hot flushes and night sweats; menstrual cycles usually regular, and hormone levels have not yet shifted;
frank signs of perimenopause take ≈2 yr to develop; pattern recognition data—obtained by quick examination of
headache questionnaire; presence of migraine mandates vascular work-up; sleep problems in perimenopausal
women—common challenge; resolved by amitriptyline
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| Patients refractory to treatment: management ineffective even though patient compliant and treatment appropriate; contributing
factors that may be overlooked—consumption of caffeine, caffeine-containing foods, and foods associated with
migraine, eg, soy, sourdough bread, excessive intake of citrus fruit; lack of aerobic exercise (deconditioning lowers headache
threshold); erratic sleep patterns (chronobiologic challenges related to sleep patterns difficult to manage); “letdown”
migraine (involves relief of emotional stress; due to change in adrenaline levels)
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| Pathogenesis: unproven; because brain cannot localize pain, neuroinflammation—in anterior two thirds of brain, produces
pain behind eye; around basilar artery produces basilar migraine with pain posteriorly and brainstem-type symptoms,
including vertigo, diplopia, and tinnitus; caveat—do not use triptans to manage basilar migraine
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| Prevention: help patient avoid potential triggers and balance factors that alter headache threshold
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| Initial inflammatory process: swelling of superficial temporal artery coincides with onset of pain and provides indicator
for initiating high-dose antiinflammatory therapy; options include 75 mg of indomethacin, high-dose naproxen
(Anaprox), or ketorolac (Toradol)
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| Onset of pounding, pulsatile pain: administer antiinflammatory agent and shut down trigeminal nerve terminals with triptans,
ergotamine tartrate and caffeine (Cafergot), or dihydroergotamine (DHE)
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| Nonpharmacologic management: indicated for headaches unresponsive to pharmacologic therapy; look for factors that
may be blocking efficacy of previous therapy; identify headache triggers—diary helps determine timing of headache
and factors that may coincide with onset
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| Biofeedback and relaxation: helpful; postpone discussion on biofeedback until patient—reassured they do not have
life-threatening cause for headache, eg, brain tumor; understands how lifestyle may contribute to problem; points—in
laboratory, patient learns to use biofeedback to lower body temperature; tingling sensation associated with sublingual
medications, eg, rizatriptan (Maxalt) or zolmitriptan (Zomig) may provide form of biofeedback
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| Pharmacologic management: patient with headache ≥3 days/wk requires preventive therapy; options for patient with—low
treatment needs (eg, headache at menstruation) include education, simple analgesics, and triptans at time of menses; intermediate
treatment needs (eg, 2 headaches/wk) include education and preventive therapy with triptan and antiinflammatory
agent; high treatment needs include preventive medication and serotonin agonist; sumatriptan (Imitrex injection)—most
effective serotonin agonist; new 4-mg dosing reduces side effects associated with 6-mg dosing; pointers—prodrome can
help patient identify impending problem and initiate therapy to block migraine; if prodrome indistinguishable from headache
phase, implement lifestyle changes to help manage problem
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| Observations: patient-monitored pain triage—patient who understands headache pattern can immediately match appropriate
medication to headache phase; narcotics—use limited to selected patients; provide global pain relief and do
not help train patient to manage pain; analgesic rebound—associated with narcotics, triptans, ergots, nonsteroidal antiinflammatory
drugs (NSAIDs; possibly), and combination analgesics containing caffeine, eg, combination of butalbital,
aspirin, and caffeine (Fiorinal); to avoid rebound, limit at-risk medications to ≤2 times/wk (unless managing
menstrual migraine with 3-day regimen)
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| Triptans: expensive; rapid onset of action; no one best drug; options—Maxalt; naratriptan and sumatriptan (Imitrex) have
fewer adverse effects; almotriptan (Axert) good as well; if efficacy of Imitrex declines at 6 hr—switch to Maxalt or
Axert; approach prolongs efficacy, eliminates double dosing, and reduces cost; options if patient too nauseated to use
oral medication—injectable Imitrex; drugs administered via nasal or sublingual routes (absorbed in gut via different
route)
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| Severe headache: rescue—meperidine (Demerol); promethazine (Phenergan); other options—intravenous (IV) droperidol
(effective; akathisia risk mandates combining drug with diphenhydramine [Benadryl]; 0.625 mg dose achieves
good results; 2.5- or 5-mg doses associated with ventricular tachycardia); valproic acid (IV Depacon)
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| Additional areas of concern: select preventive medications that can improve comorbid conditions, ie, divalproex, topiramate,
and pregabalin (Lyrica); exertional migraine—rule out aneurysmal rupture if severe headache develops after
strain; propranolol (Inderal) medication of choice
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| Rebound headache: ask patient about symptoms before onset of chronic daily headache; look for evidence of vascular issues
or tension-type headache; determine what happened before rebound response developed, eg, excessive use of Fioricet;
problems—diffuse bilateral headache can awaken patient; tolerance to migraine medications and no response to preventive
medications worst case scenario; if patient has rebound headache—administer divalproex (Depakote), topiramate (Topamax),
or propranolol and monitor tolerance; be sure patient knows drugs will not work until dosage of problem medication
reduced by ≥50%; withdrawal of overused medication—approach depends on patient’s cooperation; steroids can be
used; hospitalization unnecessary; pain medications—prednisone (when therapy lasts <2 wk); options when therapy >2
wk (triptans; oral naratriptan [Amerge] protocol effective); additional aspects—initiate prophylactic therapy; follow up at
2 to 4 wk; let patient know management will take ≈1 yr
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| Additional aspects of management: CASH mnemonic to help patient evaluate factors that may be causing deterioration
in management efficacy—caffeine intake (≤8 oz/day when migraine poorly controlled), associated foods, nasal decongestants
and herbs; aerobic exercise; sleep patterns; hormonal status; botulinum toxin type A (BOTOX)—cannot prevent
tension-type headache; prevents migraine by closing down trigeminal nerve afferents, paralyzing muscle at neuromuscular
junction and by chemical effect; indicated when patient cannot take oral medications, or fails oral therapy; point—patient
communication key
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| QUESTION AND ANSWER SESSION —Dr. Jackson; Esther Sternberg, MD, Research Professor, American University,
Washington, DC
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| Treatment of migraine during pregnancy: acetaminophen (Tylenol) and narcotics only drugs safe in pregnancy; first
trimester—problem period; initial options include Tylenol, narcotics, or office administration of IV fluid; consider triptan
therapy when initial options fail and pain and hyperemesis place fetus at risk (low-dose Amerge preferred); preventive
medications—necessary when migraine continues into second and third trimesters; calcium channel blockers and
β-blockers effective (risk for intrauterine growth retardation (IUGR) mandates consultation with obstetrician and serial
fetal ultrasonographic monitoring); cyproheptadine may make patient drowsy but otherwise safe
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| Approach to patient who wants to become pregnant, has many weekly headaches controlled by medroxyprogesterone
(Depo-Provera), and does not respond well to triptans: stabilize lifestyle factors for 3 mo (ensure patient follows preventive
protocol); withdraw Depo-Provera; avoid preventive medications; place patient on high-dose OTC riboflavin
(400 mg); address severe headaches as they occur
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| Safety of OCs in migraineurs with normal hormonal cycles: OCs contraindicated in migraineurs who—smoke; have
auras or auras with hemiparesis (indications that patient receiving procoagulant may be at increased risk for vasospasm);
low-estrogen contraceptives acceptable in patient—with aura who does not smoke; who has headaches well controlled;
has low estrogen levels; points—avoid strongly cyclic OCs in patients with aura; use lower estrogen level, with
rescue during placebo phase
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Educational Objectives
| The goal of this program is to educate the listener about the management of migraine headaches. After hearing and assimilating
this program, the clinician will be better able to:
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| 1. Identify primary nonmigrainous disorders that can complicate headache diagnosis.
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| 2. Review clinical characteristics of migraine headache.
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| 3. Explore the relationship between migraine and a woman’s hormonal cycle
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| 4. Assess various pharmacologic and nonpharmacologic options for managing migraine.
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| 5. Manage rebound headache and migraine during pregnancy.
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Discussed on This Program
Acetaminophen (N -acetyl-P -aminophenol; APAP) [Tylenol, others]
Acetaminophen and pseudoephedrine HCl[Sudafed Sinus Headache]
Almotriptan malate [Axert]
Amitriptyline HCl [Elavil]
Aspirin, acetaminophen, and caffeine [Excedrin Migraine, others]
Botulinum toxin type A [Botox, Botox Cosmetic, Dysport]
Butalbital, acetaminophen, and caffeine [Fioricet, others]
Butalbital, aspirin, and caffeine [Fiorinal, Fiortal]
Caffeine [several trade names]
Carbamazepine [Carbatrol, Epitol, Tegretol, Tegretol-XR]
Cyproheptadine HCl
Dihydroergotamine mesylate [D.H.E. 45, Migranal]
Diphenhydramine HCl [Benadryl, others]
Divalproex sodium [Depakote, Depakote ER]
Droperidol [Inapsine]
Ergotamine tartrate and caffeine [Cafergot, others]
Ethinyl estradiol and levonorgestrel [Seasonale, others]
Haloperidol [Haldol, Haldol Decanoate 50, Haldol Decanoate 100]
Ibuprofen [Motrin Migraine Pain, others]
Indomethacin [Indocin, others]
Ketorolac tromethamine [Toradol, others]
Medroxyprogesterone acetate [Depo–Provera, others]
Meperidine HCl [Demerol]
Naproxen [Anaprox, others]
Naratriptan HCl [Amerge]
Nortriptyline HCl [Aventyl HCl, Aventyl HCl Pulvules, Pamelor]
Prednisone [Several trade names and preparations]
Pregabalin [Lyrica]
Promethazine HCl [Phenadoz, Phenergan]
Propranolol HCl [Inderal, Inderal LA, InnoPran XL]
Pseudoephedrine HCl [Sudafed, others]
Rizatriptan benzoate [Maxalt, Maxalt-MLT]
Sumatriptan succinate [Imitrex]
Tizanidine HCl [Zanaflex]
Topiramate [Topamax]
Valproic acid [Depacon, others]
Zolmitriptan [Zomig, Zomig-ZMT]
Suggested Reading
Bendtsen L, Jensen R: Tension-type headache: the most common, but also the most neglected, headache disorder. Curr
Opin Neurol 19:305, 2006; Couch JR: Rebound-withdrawal headache (medication overuse headache). Curr Treat Options
Neurol 8:11, 2006; Jackson CM: Effective headache management. Strategies to help patients gain control over pain.
Postgrad Med 104:133, 1998; Lipton RB et al: Migraine diagnosis and treatment: results from the American Migraine
Study II. Headache 41:638, 2001; Scher AI et al: The comorbidity of headache with other pain syndromes. Headache
46:1416, 2006; Sheftell FD: Role and impact of over-the-counter medications in the management of headache. Neurol Clin
15:187, 1997; Sheftell FD: Understanding the headache patient with complex psychiatric comorbidities: A headache specialist’s
perspective. Headache 46 Suppl3:S165, 2006; Stewart WF, Lipton RB: Epidemiologic clues and the classification
of primary headaches. Cephalagia 14:77, 1994.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty
reported nothing to disclose.
Drs. Jackson and Sternberg were recorded at Pain Management in Women Over the Lifecycle, presented April 26-29,
2006, in San Diego, CA, by the University of California, San Diego, School of Medicine and Diana Padelford Binkley
Foundation of Solana Beach, CA.The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation
in the production of this program.
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