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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