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1
Medication Therapy
Management for
Migraine Headaches:
Appropriate Treatment Options, Patient
Education & Medication Therapy Monitoring
Ginelle Schmidt, Pharm.D.
Assistant Professor, Pharmacy Practice
Drake University
College of Pharmacy & Health Sciences
Clinical Pharmacist, Penn Avenue Internal Medicine
Email: ginelle-schmidt@drake.edu
Disclosures
Dr. Ginelle Schmidt has no
financial relationships to
disclose
2
Objectives
� At the conclusion of this program, the participant will be able to:
• Discuss current treatment guidelines for migraine
management.
• Identify appropriate over-the-counter (OTC) management for
migraines.
• Identify migraine patients that would benefit from a referral to
their physician.
• Discuss with patients practical steps for the prevention and
treatment of migraine headache.
• Discuss with patients the proper usage and importance of
adherence to migraine medications.
Introduction
� Approximately 18% of women and 6% of men in the
U.S. experience migraine
� Many go undiagnosed and undertreated
� 63% have at least one attack per month; 25% have
weekly attacks
� 9 of 10 patients endure some impairment during an
attack
� More than half of migraine sufferers only take OTC
medications or none at all
Headache 2001;41:646–657.
Pharmacotherapy 2003;23(4):494-505.
Headache.2007; 47:355 -363.
3
Headaches
� Primary Headache Disorders
• Migraines
• Cluster headaches
• Tension-type headaches
� Secondary Headaches
• Due to an underlying pathophysiology:
tumor, aneurysm, infection, etc.
• Less common
Ann Intern Med 2002;137:840-49.
Neurology 2000;55:754–763.
Findings Concerning for Secondary Headache
� Complaints of “the worst headache ever”
� First severe headache
� Worsening over days or weeks
� Pain induced by exertion
� Onset after age 50
� Headache from trauma
� Accompanied by fever and/or stiff neck
� Headache duration more than 72 hours
4
Migraines: Fact or Fiction?
� Having migraines is a sign that you have psychological
problems
� Only women have migraines
� People with migraines tend to have hypersensitive,
uptight, perfectionist, & compulsive type personalities
� Migraine is a vascular disease
� If triptans fail, then you must not have migraines
� Migraines are caused by having too much stress in your
life
� Migraines are curable
Lancet 2004;363:381–391.
Migraine Headaches
� Chronic condition
� Recurrent episodic attacks
� Gradual onset of pain, lasting 4-72 hours
� Typically unilateral, and throbbing/pulsating
� Characteristics vary among patients, and often among
attacks within a single patient
� Often accompanied by nausea (90%), vomiting (33%),
and sensitivity to light and/or noise
5
Pathophysiology of Migraine
Transmission of Pain
Impulses
Release of Vasoactive
Neuropeptides
Activation of Trigeminal
Sensory Nerve
Adapted from:
International Headache Society (IHS) Diagnostic Criteria
� Migraine without Aura
• Headache attack lasts 4-72h
• Headache has at least two of the following characteristics:
� Unilateral location
� Pulsating quality
� Moderate or severe intensity
� Aggravation by or avoidance of routine physical activity
• During Headache, at least one of the following:
� Nausea and/or vomiting
� Photophobia or phonophobia
• At least five attacks occur fulfilling above criteria
• No evidence of secondary cause
Cephalgia 2004; 24(Suppl 1):1-160.
6
Cephalgia 2004; 24(Suppl 1):1-160.
IHS Diagnostic Criteria
� Migraine with Aura
• Aura consisting of at least one of the following:
� Fully reversible visual symptoms
� Fully reversible sensory symptoms
� Fully reversible dysphasic speech disturbance
• At least two of the following:
� Homonymous visual and/or lateral sensory symptoms
� At least one aura symptom develops gradually over at least 5 minutes and/or different aura symptoms occur in succession for at least 5 minutes
• Headache fulfilling migraine criteria begins during the aura or follows the aura within 60 minutes
• At least two attacks occur fulfilling criteria listed above
• No evidence of secondary cause
Headaches
Symptom Sinus Headache Migraine Headache
Tension
Headache
Cluster
Headache
Location
Bilateral in the
cheekbones,
forehead, or bridge
of nose
Usually unilateral BilateralAlways
unilateral
Description
Gradual onset,
pulsating; moderate
to severe severity
Gradual onset,
pulsating; moderate
to severe severity
Pressure or
tightness which
waxes and wanes
Pain is deep,
continuous, and
explosive in quality;
begins quickly,
usually around one
eye
Activity Aggravated by
sudden head
movement
Aggravated by
routine physical
activity
May remain active
or may need to rest Remains active
Duration 4 to 72 hours 4 to 72 hours Variable 30 min to 3 hours
Associated
Symptoms
Nasal discharge,
feeling of fullness in
ears, or facial
swelling
Nausea, vomiting,
photophobia,
phonophobia; may
have aura
None
Tearing/redness of
the eye; pallor;
congestion; rarely
neurologic deficits
7
Phases of a Migraine Attack
Adapted from Clin Cornerstone 1999;1:21-32 and Lancet 1992;339:1203.
8
Phases of a Migraine Attack
Premonitory/Prodrome
� Photophobia
� Phonophobia
� Hyperosmia
� Difficulty concentrating
� Food cravings or anorexia
� Constipation or diarrhea
� Mood changes
� Muscle stiffness
� Fatigue
� Yawning
Aura
� Seeing flashing lights, wavy
lines, or spots
� Partial loss of sight or blurred
vision
� Olfactory hallucinations
� Vertigo
� Auditory hallucinations
� Paresthesias or numbness
involving the arms and face
Aura – Visual Disturbances
9
Neurology 2000;55;754-62.
General Principles of Management
� Establish a diagnosis
� Identify and avoid triggers
� Educate patient about condition and treatment
• Discuss the rationale for a particular treatment,
proper use, adverse events
� Establish realistic patient expectations
� Individualize treatment choice
� Create a formal management plan and individualize
management
Headache 2003; 44(4):323-327
Migraine Screening Tool
� 3 Questions
1) Do you have recurrent headaches that interfere
with work, family, or social functions?
2) Do your headaches last at least 4 hours?
3) Have you had new or different headaches in the
past 6 months?
� Migraine diagnosis
• Yes to questions 1 & 2 and a no answer to #3
10
Migraine Screening Tool
� During the last 3 months, did you have the following
with your headaches?
1) Felt nauseated or sick to your stomach?
2) Bothered by light?
3) Your headaches limited your ability to work, study, or
do what you needed to do for at least 1 day?
� If yes to 2 or more questions, you may have
migraines.
Neurology 2003; 61:375-82
Case Study
TL, a 44 year-old woman with at 15 year history of migraine
headaches. Although she typically experienced 1-2 migraine
headaches per month in the past, recently she has been having
4-5 attacks per month. TL was promoted to an executive position 5
months ago, and adjusting to the new position has been stressful at
times. It has required her to increase her overnight travel, which
has affected her sleep patterns. The job involves luncheon and
dinner meetings with associates and clients, and she enjoys this
“wining and dining” aspect of her new job. However, TL reports
that many of her migraine headaches seem to occur on these
business trips and after restaurant meetings.
• What are some likely causes of TL’s Headaches?
11
Migraine Triggers
� Weather patterns
� Bright or flickering lights
� Loud noises
� Stress
� Strong odors
� Tobacco smoke
� Excess or insufficient sleep
� Menstruation
� Foods
• Processed meats
• Aged cheese
• Alcoholic beverages, especially
red wine
• Caffeine in excess or caffeine
withdrawal
• Chocolate
• Saccharin/aspartame
• Fermented or pickled foods
Headache Diary
12
Abortive Therapy for Migraines
Matchar DB, Young WB, Rosenberg JA, et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. Available from the American Academy of Neurology [online]. Available at:
http://www.aan.com. Accessed October, 2009.
Treatment Goals of Acute Attacks
� Treat attacks rapidly and consistently without
recurrence
� Restore the patient’s ability to function
� Minimize the use of back-up and rescue medications
� Optimize self-care and reduce subsequent use of
resources
� Be cost-effective for overall management
� Minimize adverse events
13
Non-Pharmacological Approaches
� Identification and avoidance of triggers (diary)
� Regular sleep pattern
� Smoking cessation
� Exercise and healthy eating habits
� Cool or warm compress to the head and/or neck
� Rest or sleep, usually in a dark, quiet environment
� Relaxation therapy
� Biofeedback and cognitive therapy
Acute Management
� Individualize treatment
• Frequency and severity of attacks
• Presence and degree of temporary disability
• Associated symptoms (nausea/vomiting)
• Medication history
• Coexisting conditions (heart disease, pregnancy,
uncontrolled hypertension)
� Limit use of abortive therapy to ≤ 2x per week
Ann Intern Med 2002;137:840-49.
Matchar DB, Young WB, Rosenberg JA, et al. Evidence-based guidelines for migraine headache in the primary care setting:
pharmacological management of acute attacks. Available from the American Academy of Neurology [online]. Available at: http://www.aan.com. Accessed April 25, 2000.
14
Severity of Migraine
� Select medication option based on headache severity
� Degree of disability
• Mild: no disruption or minimal disruption in usual activities
• Moderate: marked functional impairment
• Severe: unable to perform usual activities (confined to bed) or can function only with severe discomfort and reduced efficiency
� Pain severity
• 10-point scale (0 for no pain to 10 for the worst pain)
• 4-point scale (0 for no pain, 1 for mild pain, 2 for moderate pain, and 3 for severe pain)
MIDAS Questionnaire
Neurology 2001;56:S20-S28
15
US Headache Consortium
� “Grade A”– multiple well designed randomized trials
relevant to the recommendation and yielded a
consistent pattern of findings
� “Grade B”– some evidence from randomized clinical
trials, but scientific support not optimal
� “Grade C”– Consortium achieved consensus on the
recommendation in the absence of relevant
randomized, controlled trials
Neurology 2000;55;754-62.
Strength of Evidence
Scientific Effect
� 0 = Medication ineffective or
harmful
� + = either not statistically or
clinically effective
� ++ = statistically significant
� +++ = Effect statistically
significant and clinically far
exceeds minimally effective
benefit
Clinical Impression
� 0 = Most people get no
improvement
� + = Somewhat effective, few
people get benefit
� ++ = Effective, some get clinically
significant improvement
� +++ = Very effective, most get
benefit
16
Abortive Therapy: Mild to Moderate Attacks
� Drugs of Choice:
• Aspirin (“A”)
• Oral NSAIDS
� Particularly useful in hormone headache
� Ibuprofen, naproxen sodium (“A”)
� Diclofenac, naproxen (“B”)
• Note: acetaminophen alone considered ineffective, but can consider in pregnancy
� Side effects:
• Dyspepsia, aspirin and other NSAIDS should be used with caution in patients with asthma, bleeding disorders, PUD, renal impairment
Neurology 2000;55;754-62.
Ann Intern Med 2002;137:840-49.
Abortive Therapy: NSAIDs & Non-opiate Analgesics
Drug Scientific
Effect
Quality of
Evidence
Clinical
Impression of
Effect
Adverse
Effects
Acetaminophen 0 B + Infrequent
Ketorolac IM + B ++ Infrequent
Aspirin ++ A ++ Occasional
Diclofenac ++ B ++ Occasional
Ibuprofen ++ A ++ Occasional
Naproxen + B ++ Occasional
Naproxen sodium ++ A ++ Occasional
Neurology 2000;55;754-62.
17
Medication Dosage Max per
24 hours
Comments
Aspirin 500-1000 mg q4-6 h 4000 mg
Ibuprofen 200-800 mg q6 h 2400 mg
Naproxen Sodium 550-825 mg at onset 1375 mg May repeat 220
mg in 3-4 h
Diclofenac potassium 50-100 mg at onset 150 mg May repeat 50 mg
in 8 h
Acetaminophen 1000 mg q4-6 h 4000 mg
APAP 250mg/ ASA
250mg/ Caffeine 65mg
1-2 tablets q4-6 h 12 tabs Excedrine Migraine
APAP or ASA with
butalbital/caffeine
1-2 tablets/capsules
q4-6 h
6 tabs/caps
Isometheptene 65mg/
dichloralphenazone
100mg/ APAP 325mg
2 capsules at onset 5 caps Repeat 1 capsule
every hours prn
Midrin
Micromedex Online: accessed 10/09
NSAIDs and Non-Opiate Analgesics –Migraine Dosage Recommendation
Over-the-Counter Medications
� Six of every ten patients
exclusively use OTC meds to
treat migraines
� Pharmacists suggest a migraine
pain agent nearly 16,000x per
day
� Use of OTC meds has remained
stable over last decade
Headache 2001;41:638-45.
Headache 2001;41:646-57.
18
Abortive Therapy: Moderate to Severe Attacks
� Ergot Alkaloids and Derivatives
• Preparations:
� Dihydroergotamine (nasal spray – Migranal, injection-DHE-45)
� Ergotamine (sublingual – Ergomar, Ergostat)
� Ergotamine/caffeine (tablets – Wigraine, suppositories – Cafergot)
• Mechanism of action:
� blockade of neurogenic inflammation in the trigeminal system through stimulation of 5-HT1 receptors
Abortive Therapy: Moderate to Severe Attacks
� Ergot Alkaloids and Derivatives Continued
• Side Effects: N/V, ↑BP, diarrhea, numbness or tingling in fingers or toes
� Nasal Spray: rhinitis, pharyngitis, altered sense of taste
� Ergotism: extreme cases with severe peripheral
ischemia and development of gangrene
• Contraindications: coronary artery disease, hypertension (uncontrolled), peripheral vascular disease, liver/kidney disease, pregnancy category X, use within 24 hrs of selective 5-HT1 receptor agonists
19
Abortive Therapy: Ergot Alkaloids and Derivatives
Drug Scientific
Effect
Quality of
Evidence
Clinical
Impression of
Effect
Adverse
Effects
DHE IV ++ B + Frequent
DHE SQ +++ B ++ Occasional
DHE IM ++ A ++ Occasional
DHE nasal ++ B ++ Occasional
Ergotamine + B ++ Frequent
Ergotamine plus
caffeine
+ B ++ Frequent
Neurology 2000;55;754-62.
Abortive Therapy:Moderate to Severe Attacks
� Selective 5-HT1 Receptor Agonists (“A”)
• “Triptans”
• Effective and relatively safe
• Appropriate initial choice in patients with moderate to severe migraine
• Good choice when non-specific medication has failed
• Use intranasal or SQ forms if N/V present
• Mechanism of Action: high affinity for 5-HT1B and
5-HT1D receptor subtypes, leading to cranial vasoconstriction, inhibition of neuropeptide release, and reduced transmission in the pain pathways
Neurology 2000;55;754-62.
20
Abortive Therapy: Moderate to Severe Attacks
� Selective 5-HT1 Receptor Agonists Continued
• Side Effects: Sensation of warmth, fatigue,
dizziness, tingling, chest tightness, weakness, and
somnolence
• General Contraindications: Ischemic heart disease,
coronary artery disease, or uncontrolled
hypertension, within 24hr of ergot preparations or
other triptans, pregnancy category C
21
CNS Drugs 2007; 21 (11): 877-883
FDA’s MedWatch available on line at http://www.fda.gov/medwatch/report.htm
Safety of Triptans
� Craniovascular selectivity is similar between the various triptans
• Probably accounts for the apparent lack of coronary artery
effects
• Safety likely similar for all triptans when used at recommended
doses
� OTC availability in UK and Germany
� July 2006- FDA issued alert
• 27 case reports serotonin syndrome with triptans and SSRIs
or SNRIs
• Risk low, should counsel patients on signs/symptoms
� Use should be limited to no more than 9 days per month
Drug Specific Contraindications of Triptans
� Severe renal impairment (naratriptan)
� Severe hepatic impairment (eletriptan/ naratriptan/
zolmitripan NS)
� MAOIs within 2 weeks (sumatriptan, rizatriptan,
zolmitriptan)
� Potent CYP3A4 inhibitors within 72 hrs (eletriptan)
� Concomitant use with propranolol (dosage adjustment
required with rizatriptan)
22
Abortive Therapy: TriptansSummary of Evidence
Drug Scientific
Effect
Quality of
Evidence
Clinical
Impression of
Effect
Adverse
Effects
Sumatriptan
(SQ)
+++ A +++ Frequent
Sumatriptan
(Nasal)
+++ A +++ Occasional
Sumatriptan +++ A +++ Occasional
Naratriptan ++ A ++ Infrequent
Rizatriptan +++ A +++ Occasional
Zolmitriptan +++ A +++ Occasional
Neurology 2000;55;754-62.
Case Study
TY is a 40 year old woman with a left temporal headache that
begins at 9 am. She avoids taking medication in the hope that the
headache will stop on its own. By 11:30 am the headache has
reached a moderate intensity, and she elects to take ibuprofen
200mg. An hour later the headache has not improved, and she
repeats the 200mg dose of ibuprofen. By 1 pm, the migraine pain
is severe. TY decides it is time to take her naratriptan, but tries just
a half of a tablet. Although the medication has little effect, TY
follows the directions on her prescription label and waits 4 hours to
repeat the dose, but gets no relief. The pain is now so intense that
waves of N/V start to come over her. She decides to seek care at
her local ER.
• What could TY have done to help prevent the ER visit?
23
Case Study Continued
� What could TY have done to prevent the ER visit?
• A. Take ibuprofen earlier, at the onset of the
headache
• B. Take a larger dose of ibuprofen
• C. Take naratriptan at the onset of the headache,
instead of ibuprofen
• D. Take a larger dose of naratriptan
• E. Any one of the above
Generic
Name
Brand
Name
Usual dosage
range
Time to repeat
dose (hr)
Max dose per
24 hours
Almotriptan Axert 6.25 to 12.5 mg orally 2 25 mg
Eletriptan Relpax 20 to 40 mg orally 2 80 mg
Frovatriptan Frova 2.5 mg orally 2 7.5 mg
Naratriptan Amerge 1 to 2.5 mg orally 4 5 mg
Rizatriptan Maxalt 5 to 10 mg orally 2 30 mg
Maxalt-MLT 5 to 10 mg orally 2 30 mg
Sumatriptan Imitrex Oral: 25 to 100 mg
orally
2 200 mg
Nasal Spray: 5 to 20
mg nasally
2 40 mg
Injection: 6 mg SQ 1 12 mg
Zolmitriptan Zomig 1.25 to 5 mg orally 2 10 mg
Zomig-ZMT 2.5 to 5 mg orally 2 10 mg
Zomig nasal spray 5 mg (1 spray) nasally 2 10 mg
Comparative Dosage Table - Triptans
Micromedex Online: accessed 10/09
24
Comparison of Available Triptans*
Drug Route Onset Tmax T 1/2 Comments
Amerge1
(naratriptan)
Oral 1-3 hr 2-3 hr Long
6h
-Not contraindicated with MAOIs
-Fewer side effects
-Repeat dosing in 4 hours
Axert
(almotriptan)
Oral 30 min –
2 hr
1-3 hr Short
3h
-May be better tolerated than sumatriptan
Frova1
(frovatriptan)
Oral 2-3 hr 2-4 hr Long
26h
-Longest half-life
- Not contraindicated with MAOIs
Imitrex1
(sumatriptan)
Oral 20-30
min
2.5 hr Short
2.5h
-First oral triptan available
-Works as well as injectable but not as fast
Imitrex1
(sumatriptan)
Nasal
spray
15 min 1-1.5
hr
Short
2h
-Bad taste
-Rapid acting alternative to injection
Comparison of Available Triptans*
Drug Route Onset Tmax T 1/2 Comments
Imitrex1
(sumatriptan)
SQ Inj 10-15 min 12 min Short
2h
-Injection site pain
- Repeat dosing in 1 hour
- Good choice if N/V present
Maxalt and
Maxalt MLT
(rizatriptan)
Oral 30 min –
2 hr
1-1.5 hr
(tab)
1.5-2.5 hr
(MLT)
Short
2-3h
-Maxalt MLT tablets may be taken without
water
-Dosage adjustment required if taken with
propranolol
Zomig1
and ZMT
(zolmitriptan)
Oral 45 min 2-3 hr Short
3h
- ZMT may be taken without water
Zomig1
(zolmitriptan)
Nasal
spray
15 min 3 hr Short
3h
-Bad taste
- Rapid acting alternative to inj.
Relpax
(eletriptan)
Oral 1 hr 2 hr Short
4h
-Avoid with CYP3A4 inhibitors (verapamil,
clarithromycin, etc)
-Absorption ↑ by high fat
- Not contraindicated with MAOIs
*All the triptans described chart share the following features: Safety in pregnancy: Category C – should only be used if potential benefits justify potential
risk; Contraindications: Patients known to have or be at risk for ischemic heart disease, uncontrolled HTN, hemiplegic or basilar migraines. 1- Product
information. Copyright © 2002 by Therapeutic Research Center
25
Triptan Combo
� Treximet
• 85mg sumatriptan/ 500mg naproxen
• Recommend trial of monotherapy triptan first
• Dosing: 1 tablet PO at migraine onset
� May repeat dose once after 2 hours
� Max of 2 tablets in 24 hr
Neurology 2000;55;754-62.
Abortive Therapies: Moderate to Severe Attacks
� Combination Analgesics
• Acetaminophen, Aspirin, Caffeine (Excedrin
Migraine)
• Acetaminophen, Isometheptene mucate,
Dichloralphenazone (Midrin, Epidrin)
• Acetaminophen or Aspirin, butalbital, and caffeine,
with or without codeine (Fioricet, Fioricet with
codeine, Fiorinal, Fiorinal with Codeine)
26
Neurology 2000;55;754-62.
Abortive Therapies: Severe Attacks
� IM or IV DHE
� Subcutaneous or oral selective 5-HT1 agonists
� IM or IV ketorolac (Toradol)
� IM, IV, intranasal, or oral opioids
• Butorphanol nasal spray (Stadol NS)
• Meperidine Injection (Demerol)
• Tramadol tablets (Ultram)
Abortive Therapies: Severe Attacks
� Key points about Opioids
• Minimize use to prevent tolerance, physical and
psychological dependence, and abuse
• Medication overuse headache
• Reserve as “last resort”
• Relieve pain and promote sleep
27
Abortive Therapy: Combination Analgesics and Other Medications
Drug Scientific
Effect
Quality of
Evidence
Clinical
Impression of
Effect
Adverse
Effects
APAP/ASA/Caff +++ A ++ Infrequent
Butalbital/ASA/Caff ? C +++ Occasional
Butalbital/ASA/Caff/Co
deine
++ B +++ Occasional
Butorphanol nasal +++ A +++ Frequent
APAP/codeine ++ A ++ Occasional
Parenteral opiates ++ B ++ Frequent
Isometheptene + B ++ Infrequent
Neurology 2000;55;754-62.
APAP = acetaminophen; ASA = aspirin; Caff = caffeine
Abortive Therapy
� General Principles:
• Therapy is more effective if given early in the course
of the headache
• Large single doses tends to work better than
repetitive small doses
• Select a non-oral route of administration if significant
nausea or vomiting
• Select a medication based on severity of attack
28
Abortive Therapy
� General Principles Continued:
• Many oral agents are ineffective because of poor
absorption secondary to migraine-induced gastric stasis
• Use migraine specific agents for severe migraine or in
patients who respond poorly to NSAIDs or combination
analgesics
• Consider a self-administered rescue medication for
patients with severe migraines
• Use prophylactic medications in patients with frequent
headaches
Neurology 2000;55;754-62.
N Engl J Med 2002;346:257–270
Migraine Prophylaxis
29
Migraine Prophylaxis
� When to consider preventive therapy:
• Migraines produce substantial disability despite
acute therapy
• Frequent attacks requiring abortive therapy more
than twice per week (increased risk of medication
overuse headache)
• Abortive therapy ineffective, contraindicated, or
produces intolerable side effects
• Patient preference to limit the number of attacks
Neurology 2000;55;754-62.
Cephalalgia 2002;22:491–512.
Treatment Goals of Long-Term Management
� Reduce attack frequency and severity
� Reduce headache-related distress and psychological symptoms
� Reduce disability
� Improve quality of life
� Avoid acute headache medication escalation
� Educate and enable patients to manage their disease
Matchar DB, Young WB, Rosenberg JA, et al. Evidence-based guidelines for migraine headache in the primary care
setting: pharmacological management of acute attacks. Available from the American Academy of Neurology [online].
Available at: http://www.aan.com. Accessed April 25, 2000.
Neurology 2000;55;754-62.
30
Preventive Therapies for Migraine
Neurology 2000;55;754-62.
Am Fam Physician 2006;73:72-80.
31
Case Study
SF is a 28-year-old woman with long-standing migraine headaches, occurring on average every 1-2 months. The headache is easily relieved with sumatriptan 100 mg PO, however, with her last dose she experienced substernal chest pain. She reported to her local ER and had a complete work-up. MI was ruled out, however her blood pressure was found to be slightly elevated at 145/92 and she was placed on lisinopril 10 mg daily. Which of the following drugs should she use for her migraine headaches.
• A. Continue sumatriptan
• B. Naproxen sodium
• C. Hydrocodone/acetaminophen
• D. Prophylaxis with propranolol
Preventive Therapies for Migraine
� Can reduce headache frequency by ≥ 50%
� Only propranolol, timolol, valproate, and topiramate are currently approved by the FDA for migraine prophylaxis
� Consider side effect profile and co-morbid conditions
• Depression, insomnia, fibromyalgia – TCA
• Hypertension or angina – beta blocker or CCB
• Constipation or edema – avoid CCB
• Coexisting seizure disorder – antiepileptics
32
Migraine Prophylaxis
� Trial of 2-3 months needed to fully assess efficacy
� Drug doses for migraine prophylaxis are often lower
than those necessary for other indications
� Initiate low doses and slowly advance dose as needed,
as tolerated
� Continue for at least 3 to 6 months after the frequency
and severity of headaches have diminished, then may
consider tapering to a lower dose or discontinuing the
medication
Neurology 2000;55:754–763.
Cephalalgia 2002;22:491–512.
London: Martin Dunitz, 2002:21–33, 69–128.
Other Important Considerations
� When to Refer
� Medication Overuse
Headache
� Alternative Therapies
� Antiemetics
� Special Treatment Situations
33
Exclusions to Self-Care
� Symptoms concerning for secondary headache
� Use of abortive medication > 2 times/week
� OTC therapy ineffective or not tolerated
� Severe head pain or disability despite OTC therapy
� Age ≤ 7 years old
Handbook of Non-Prescription Drugs: An Interactive Approach to Self-Care, 15th Edition, 2005
When to Refer: Assessing Patients in the Community Setting
� What percentage of your headaches prohibit you from
performing normal activities and/or are accompanied by
vomiting?
� How many days per month are you completely
headache free?
� What symptoms accompany your headache?
� What OTC products have you tried?
Pharmacotherapy 2003;23(4):494-505.
34
Pharmacotherapy 2003;23(4):494-505.
When to Refer
� Question 1: If ≥ 50% disability or ≥ 20% accompanied
by vomiting – poor candidate for OTC only therapy
� Question 2: Headache free on ≤ 15 days/month
� Question 3: Any symptom suggestive of secondary
headache
� Question 4: Patients who have already tried two or more
distinct OTC medications without relief
Ann Intern Med 2002;137:840-49.
Cephalalgia 2004;24(Suppl 1):1–151. London: Martin Dunitz, 2002:21–33, 69–128.
Neurology 2000;55:754–763.
Medication Overuse Headache (MOH)
� Synonymous with “drug-induced headache”
• Not synonymous with “rebound headache”
� Results from frequent use of abortive therapy
• Risk increases when abortive medication used more than
2x per week
� Pattern of increasing headache frequency
• Often daily
� Discontinue offending agent
� Consider preventative therapy
35
* Recognized by the American Academy of Neurology as possible preventative treatments for migraine
Supplements for migraine. Pharmacist’s Letter/Prescriber’s Letter 2005;21(4):210414.
Alternative Therapies
� Feverfew*
• Dose 50-100 mg daily (whole feverfew leaf capsules)
� Riboflavin (vitamin B12)*
• Dose 400mg daily
• Turns urine yellow
� Magnesium *
• Start at 64mg twice daily (usual dose 300mg per day)
• Titrate slowly to reduce GI adverse effects
� Caffeine
• FDA-approved for use in combination with APAP and ASA
� Coenzyme Q10
� Butterbur root
Antiemetics
� Nausea and/or vomiting may prohibit use of oral medications
• Many agents cause nausea (Ergots and opioids)
� Antiemetic agents can be used as adjunct therapy
• Chlorpromazine, Prochlorperazine, Metoclopramide
• Begin at first sign of headache to reduce nausea, prevent
vomiting, and potentially allow use of PO meds
• Consider alternative dosage form products
� Direct comparison between antiemetics found that
prochlorperazine IV and IM was significantly superior to
metoclopramide in the corresponding forms
Matchar DB, Young WB, Rosenberg JA, et al. Evidence-based guidelines for migraine headache in the primary care
setting: pharmacological management of acute attacks. Available from the American Academy of Neurology [online].
Available at: http://www.aan.com. Accessed April 25, 2000.
36
Menstrual Migraines
� Nearly 60% of female migraineurs report a menstrual
link to their migraine attacks
� About 14% meet the criteria for menstrual migraine
� Consider preventative therapies perimenstrually
• NSAIDS
• Use of a monophasic low-dose combination
contraceptive in a continuous fashion would
theoretically help the migraine condition by keeping
estradiol levels steady
https://www.americanheadachesociety.org/assets/Hutchinson.pdf
Pregnancy
� Migraines often improve after the first trimester
� Give a trial to nonpharmacologic options first
� Abortive Therapies:
• NSAIDs, Acetaminophen, Codeine/narcotics
• Ergots (X), Sumatriptan
(C; most practitioners advise to avoid this)
� Prophylaxis:
• Avoid if possible; β-Blockers most commonly used
(possible intrauterine growth retardation)
� Antiemetics
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Other Special Treatment Situations
� Headache Recurrence
• Return of headache pain, usually within 24 hrs, after
an initially good response to medication
� Status Migraine
• IV DHE Q8h, combined with metoclopramide
for 2-3 days
• Chlorpromazine 25mg IV or Prochlorperazine 10mg IV
• Dexamethasone or methylprednisolone IM
• Can combine treatments
Conclusion
� Migraine is associated with
significant disability
� Abortive therapies should be
selected based on the
individual patient and
severity of attack
� Preventive medications can
reduce migraine frequency
by 50%
� Patient education and
involvement is crucial
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Additional Resources
• International Headache Society (IHS) Classification and Diagnostic
Criteria under the IHS Guidelines: http://www.i-h-s.org/
• National Headache Foundation:
http://www.headaches.org/
• American Headache Society (AHS):
http://ahsnet.org
• U.S. Headache Consortium Guidelines:
https://www.americanheadachesociety.org/professionalresources/
USHeadacheConsortiumGuidelines.asp
• American Academy of Neurology Guidelines:
http://www.aan.com/go/practice/guidelines
• European Federation of Neurological Sciences Guidelines:
http://www.efns.org/fileadmin/user_upload/guidline_papers/EFNS_guidel
ine_2009_drug_treatment_of_migraine.pdf
Questions?
Ginelle Schmidt, Pharm.D.Drake University College of Pharmacy and Health Sciences
Des Moines, Iowa; Email: ginelle.schmidt@drake.edu
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