Prevent, Treat, Repeat:

Getting Ahead of

Migraines

Jennifer Bestard

MD

FRCPC Neurology

Faculty/Presenter Disclosure

• Presenter: Jennifer Bestard

• Relationships that may introduce potential bias and/or conflict of

interest:

– Grants/Research Support: Jennifer Bestard has received grants

from Allergan and Tribute to provide CME lectures on headache.

– Speakers Bureau/Honoraria: Jennifer Bestard has received a

speaker fee and expense support from the Alberta College of

Family Physicians; Jennifer Bestard has received honoraria from

Allergan and Tribute to provide CME lectures on headache.

– Consulting Fees: N/A

– Other: N/A

Disclosure of Commercial Support

This program is presented by the Alberta College of Family

Physicians (ACFP) without any commercial or in-kind support.

The ACFP provides a speaker fee and expense support for presenting at the

Practical Evidence for Informed Practice.

• Potential for bias/conflict of interest due to commercial

support:

– Jennifer Bestard has received grants and/or honoraria for presenting CME

relating to a topic being discussed in this program and/or presentation.

Managing Sources of Potential Conflict and/or Bias

• Material/Learning Objectives and/or session descriptions were

developed and reviewed by the Planning Committee composed of

experts/family physicians/allied care professionals responsible for

overseeing the program’s needs assessment and subsequent

content development to ensure accuracy and fair balance.

• Consideration was given by the Planning Committee to identify

when speakers’ personal or professional interests may compete with

or have actual, potential, or apparent influence over their

presentations.

• Information and/or recommendations in the program are evidence-

and/or guidelines-based, and the opinions of the independent

speakers will be identified as such.

Presentation Outline

• Migraine backgrounder: Assessment, diagnosis and identification of migraine

• Treatment options for acute migraine Pharmacologic and non-pharmacologic

• When should prevention be started? 15 or more headache days per month

Steps to Diagnosing Headache Disorders

Courtesy of The American Headache Society

Diagnostic Presentation & Classification of Chronic HA

Case Vignette (Sara)

Initial

Consult

• 25-year-old female who presents to her

primary care doctor with a four year

history of headache

Frequency • Two attacks per month

Prodrome • Dysphoric mood

Aura • Zig-zag lines and a graying of vision in

a visual field

Pain • Unilateral (R>L) throbbing severe pain

lasting 24 hours untreated

Symptoms • Nausea, photophobia, unable to

function

Treatment • Excedrin Migraine up to six per day

Exam • WNL (within normal limits)

Diagnosis • ?

Primary or Secondary Headache?

Detailed History and Examination

No

Yes

Evaluate for Secondary Headache

Red Flags? Diagnose Primary

Headache Disorder

Step 1

S Systemic signs or symptoms Fever, weight loss, malignancy, HIV, meningismus, pregnancy

N Neurologic signs or symptoms Papilledema, hemiparesis, hemi-sensory loss, diplopia, dysarthria

O Onset “Worst headache of life” (thunderclap)

O Older New headache at age ≥50

P Progression of existing headache disorder

Change in quality, frequency, or location

13. Dodick DW. Adv Stud Med 2003;3:S550-S555.

Red Flags in Headache: “SNOOP”

Sara has a Primary Headache Disorder

• Sara has no headache alarms

• Four year history, lack of alarms and

normal exam, additional work-up is

not necessary

Categorize Primary Headache Disorder Step 2

Divide into headache syndromes

Short Duration

< 4hr duration

Episodic

(Long Duration)

≥ 4hr duration

≤ 15 days/month

Chronic Daily

Headache

≥ 4hr duration

≥ 15 days/month

1 2 3

Categorize Into One of Three Groups

Primary Headaches

Assess frequency and duration for each

headache type

Step 2

Diagnose the Specific Disorder

Within the Category

• Migraine vs. tension type headache

• Tension type headache is the most common primary headache

• Migraine is the leading headache disorder that causes patients to seek treatment

Differential Diagnosis Step 3

Diagnostic Criteria

Migraine without Aura:

A. At least five attacks fulfilling criteria B-D

B. Headache attacks lasting 4-72 hr

C. Headache has 2 of the following characteristics:

1. Unilateral location

2. Pulsating quality

3. Moderate or severe pain intensity

4. Aggravation by or causing avoidance of routine physical activity (e.g., walking,

climbing stairs)

D. During headache 1 of the following:

1. Nausea and/or vomiting

2. Photophobia and phonophobia

E. Not attributed to another disorder

22. International Headache Society,2nd edition. Cephalalgia 2004;24 Suppl 1:1-160.

24. Kriegler JS. In: Tepper SJ and Tepper DE, eds. The Cleveland Clinic Manual of Headache Therapy (New York, NY: Springer), 2011.

Sara has “Classic Migraine”

Migraine with Aura

• Complex array of symptoms

reflecting focal cortical or brainstem

dysfunction

• Gradual evolution: 5-20 minutes

(<60 minutes)

• May or may not be associated with

headache

• Visual > sensory >, language,

brainstem >motor*

Diagnosed Migraine:

“Tip of the Iceberg”

Diagnosed 29% 41%

31. Lipton RB et al. Arch Intern Med 1992;152(6):1273-1278.

Undiagnosed 71% 59%

Males Females

Migraine: Additional Features

• Predictable timing around menstruation or ovulation

• Stereotypical prodromal symptoms

• Characteristic triggers

• Abatement with sleep

• Positive family history

• Childhood precursors (motion sickness,

episodic vomiting/vertigo)

• Osmophobia

36. Pryse-Phillips WEM et al. Can Med Assoc J 1997; 156(9):1273-87.

Three-Item ID Migraine Screener *

During the last three months, did you have any of the following with your headaches:

28. Lipton RB et al. Neurology 2003;61(3):375–382.

* An affirmative response on 2 of 3 questions yields a sensitivity and specificity of 81% and 75%, respectively.

Item Yes / No

You felt nauseated or sick to your stomach when you had a headache?

Yes □ No □

Light bothered you (a lot more than when you don’t have headaches?)

Yes □ No □

Your headaches limited your ability to work, study or do what you need to do for at least one day?

Yes □ No □

Migraine: A Common Episodic

Headache Disorder

Neurologic disorder• Strong genetic component (up to 50%)

Global prevalence: >10%• Women: 15%–17%

• Men: 6%–9%

Two major subtypes• Without aura (~75%)

• With aura (~25%)

Burden• Among the world’s 20 most disabling diseases (WHO)

• Affects 3 million women and 1 million men in Canada An Angus Reid poll suggests that the cost of migraine in the workplace is

approximately $500 million annually

35. Pietrobon D. Neuroscientist. 2005;11(4):373–386. 41. Stovner LJ et al. Cephalalgia. 2007;27(3):193–210. 26. Linde M. Acta Neurol Scand.

2006;114(2):71–83. 22. ICHD. Cephalalgia. 2004;24 Suppl 1:1-160. 24. Kriegler JS. In: Tepper SJ and Tepper DE, eds. The Cleveland Clinic

Manual of Headache Therapy. (New York, NY: Springer), 2011. 20. Hu XH. et al Arch Intern Med. 1999;159(8):813–818.

Prevalence of Migraine and

Tension-type Headache in Various Settings

12

75

40

16

0

10

20

30

40

50

60

70

80

Population Waiting Room

Migraine Tension-Type Headache

28. Lipton RB et al. Neurology 2003;61(3):375–382.

Perc

en

t

Migraine is Often Misdiagnosed

27. Lipton RB et al. Headache 2001; 41(7):638-645.

† Inaccurate diagnosis received by migraine patients

Tension-type

Headaches

Sinus

Headaches

Cluster

Headaches

% MISDIAGNOSIS†

44%

43%

18%

Tension-Type Headache

A. At least 5 attacks fulfilling criteria B-D

B. Headache attacks lasting 30 min – 7 days (untreated or unsuccessfully

treated)

C. Headache has 2 of the following characteristics:

• Bilateral location

• Pressure non pulsating quality

• Mild to moderate pain intensity

• Not aggravated by or causing avoidance of routine physical activity

D. During headache 1 of the following:

• No nausea or vomiting

• Photophobia or phonophobia but not both

E. Not attributed to another disorder

Headache Classification Subcommittee of the International Headache Society, 2004

Why is Migraine Frequently Mistaken

for Sinus Headache?

• Pain is often located over the sinuses

• Migraine is frequently triggered by weather changes

• Tearing and nasal congestion are common during attacks

• Sinus medication may help migraine

Planning and

Management Strategies

The Art and Science of Evaluating and Treating Migraine

What might be your

preliminary treatment

recommendation for her?

Back to Sara…

Formulate a Specific Treatment Plan

Non-pharmacologic approaches

• Trigger identification and management

Identify triggers by history

Headache diaries

• Education and enhance self-efficacy

• Sleep, exercise, diet and caffeine

• Biofeedback and cognitive behavioural treatment

Specific Treatment PlanStep 4

Headache Journal

Medication Classes

in Acute Migraine Treatment

Health Canada-Approved Prescription Medications

Triptans24 • naratriptan

• almotriptan

• frovatriptan

• sumatriptan

• rizatriptan

• eletriptan

• zolmitriptan

Ergots24 • ergotamine tartrate

• dihydroergotamine

NSAID9 • diclofenac potassium for oral solution (CAMBIA)

Other Medications Used in Migraine Treatment24

NSAIDs Opioids Barbiturates

24. Kriegler JS. In: Tepper SJ and Tepper DE, eds. The Cleveland Clinic Manual of Headache Therapy. (New York, NY: Springer), 2011.

9. CAMBIA Product Monograph. Tribute Pharmaceuticals Canada Ltd. March 9, 2012.

• No other prescription medications have met the criteria for Health Canada approval for

treatment of acute migraine

Principles of Acute Treatments

1. Stratified care

2. Early intervention

3. Use correct dose and formulation

4. Treat at least two or three attacks before

judging acute medications

5. Use a maximum of 2-3 days / week

6. Use preventive therapy in selected patients

38. Silberstein SD. Neurology 2000; Sep 26;55(6):754-62.

32. Lipton RB, et al. JAMA 2000;284(20):2599-2605.

Define the needs: clinical judgment

Stepped care within attacks: according to immediate effect

Acute Management: Migraine Stratified Care

Triptans

(Ergots)

Opioids (rarely)

Combination OTC

Prescription NSAIDS

Triptans

OTC analgesics

High

Low

Moderate

Follow-up Visits

39. Silberstein SD et al. Wolff’s Headache And Other Head Pain, Seventh Edition (New York: Oxford University Press Inc), 2001 .

Review outcome measures (diaries, MIDAS, etc.)

Assess efficacy, adverse effects, and satisfaction with current regimen

If treatment is not working, find out why?

Consider:

• Primary failure

• Effects take to long

• Poor consistency

• Recurrence

• Adverse events

• Interfering medications

• Expectations unrealistically high

Sara – Age 35

• Working full-time as a social worker

• Married with 3 kids under age 6

• Headache frequency has increased

very gradually over the last 3 years

• Headaches are now occurring

about 3-4 days per week

• Otherwise well, no change in

headache characteristics, no new

meds

What is the Diagnosis?

How Would You Manage Sara’s Headaches?

Sara – Age 35

Chronic Migraine

Chronic migraine:

• HA on ≥15 days/mt for >3 mts

• ≥8 days fulfilling criteria for

migraine with or without aura,

responding to migraine-

specific medications, or

recognized by patient as

migraine

• Not better accounted for by

another ICHD-3 beta diagnosis

Preventive Treatment:

When?

• When patient has ≥15 headache days per month

• When ≥4 severe attacks per month poorly controlled with symptomatic

medication

• When symptomatic medication needs to be used more than 2-3 days a

week

• Special situations preclude the use of effective acute medications

For how long?

• 3 month minimum trial

• If helpful, consider reduction and cessation after 12-18 months

Goals of Chronic Migraine Therapy

16. Gladstone J and Dodick DW. Practical Neurology 2004;4:6-19.

Reduce (1 or more of):• Headache frequency

• Duration

• Severity

• Medication requirements

• Headache-related disability

What to expect?• 50% obtain a reduction of ≥50% in the frequency of attacks in the

second or third month of use

Monotherapy vs. Polytherapy?• Monotherapy preferred but polytherapy may be necessary

• Antidepressants

• TCAs (i.e. amitriptyline,

nortriptyline)

• Beta blockers

• Propranolol, Nadolol

• Anticonvulsants

• Topiramate

• Divalproex

• Gabapentin

• Calcium channel blockers

• Verapamil

• Flunarizine

• Interventional

• Botulinum toxin A (BOTOX)

• ? Nerve blocks

• Miscellaneous

• Pizotifen (Sandomigran)

• Angiotensin II receptor

antagonist ?

• “Natural” Options

• Riboflavin, feverfew, magnesium

Preventive Medications

Overall Summary – Clinical Pearls

• Migraines are the most common headache-type leading to

medical attention (occurs in pediatric and adult population).

• Acute migraine management requires stratified care which

may include OTC, NSAIDS and/or triptan and/or anti-emetic.

• Lifestyle strategies are critical for preventing migraine

headaches and patients should be constantly reminded about

them.

• When migraines are too frequent/disabling, consider

prophylactic therapy (start low, go slow, and persist).

• Watch out for medication overuse headache and, when

present, aggressively manage.

The Art and Science of

Evaluating and

Treating Migraine

THANK YOU

ICHD-3 (beta) Definition

ICHD: International Classification of Headache Disorders.Headache Classification Committee. Cephalalgia 2013;33:629-808.

Medication overuse (MOH)*

≥15 HA days/mt in a patient with a pre-existing HA

disorder

Regular overuse for >3 mts of ≥1 acute meds

Not better accounted for by another ICHD-3b

diagnosis

*Also called transformed migraine, rebound headache

CM: Current State of Classification & Diagnosis

Classification of MOH

Headache Classification Committee. Cephalalgia 2013;33:629-808.

ICHD: International Classification of Headache Disorders; MOH: medication overuse headache; ASA: acetylsalicylic acid; NSAID: nonsteroidal anti-inflammatory drug

Overuse (≥15 days/mt for >3 months) of:

Overuse (≥10 days/mt for >3 months) of:

Acetaminophen Ergotamines

ASA Triptans

Other NSAIDs Opioids

Combination analgesics

Combinations of ergotamine, triptans, simple analgesics, NSAIDs and/or opioids

ICDH-3 Beta Diagnostic Criteria: Fulfills criteria for MOH plus…

Recognition and Diagnosis of MOH

Screening For MOH

Kristoffersen ES et al. J Neurol Neurosurg Psychiatry 2015;86:505-12.

HA: headache; MOH: medication overuse headacheRecognition and Diagnosis of MOH

BIMOH (Brief Intervention for MOH) Scoring

Do you think your use of HA medication was out of control? 0 = never/almost never 1 = sometimes 2 = often 3 = always/nearly always

Did the prospect of missing a dose make you anxious or worried? 0 = never/almost never 1 = sometimes 2 = often 3 = always/nearly always

Did you worry about your use of your HA medication? 0 = never/almost never 1 = sometimes 2 = often 3 = always/nearly always

Did you wish you could stop? 0 = never/almost never 1 = sometimes 2 = often 3 = always/nearly always

How difficult would you find it to stop or go without your HA medication?*

0 = not difficult 1 = quite difficult 2 = very difficult 3 = impossible

Cut-off scores for risk of MOH≥5 for women

≥4 for men

Screening for MOH in Primary Care

Dousset V et al. J Headache Pain 2013;14:81.

Recognition and Diagnosis of MOH

• Sensitivity 95.2%, specificity 80%

• Advantages:

– Simple

– Quick

– Low cost

Quick 2-question screen for MOH

1 Do you take a treatment for attacks on ≥10 days/month?

2 Is this intake on a regular basis?

Established CM With MOH: Treatment Strategies

Tepper. Neurology Continuum 2012 ;18:807-22.

Wean overused medication(s)

Encourage use of non-pharmacological

approaches

Switch to effective preventive treatment

and place limits on acute meds

Education

MOH: medication overuse headache; CM: chronic migraine

Management Strategies

Bibliography

References:

1. Acute treatment of migraine attacks: efficacy and safety of a nonsteroidal anti-inflammatory drug, diclofenac-potassium, in comparison to oral sumatriptan and placebo. The Diclofenac-K/Sumatriptan Migraine Study Group. Cephalalgia 1999;19(4):232-240.

2. Aurora SK, Kori SH, Barrodale P, et al. Gastric stasis in migraine: more than just a paroxysmal abnormality during a migraine attack. Gastric stasis in migraine: more than just a paroxysmal abnormality during a migraine attack. Headache 2006;46(1):57-63.

3. Aurora SK, Kori SH, Barrodale P, et al . Gastric stasis occurs in spontaneous, visually induced, and interictal migraine. Headache2007;47(10):1443-1446.

4. Bigal ME, Serrano D, Buse D, et al. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache 2008;48(8):1157-1168.

5. Boyle R, Behan PO, Sutton JA. A correlation between severity of migraine and delayed gastric emptying measured by an epigastric impedance method. Br J Clin Pharmacol 1990;30(3):405-409.

6. Brandes JL, Kudrow D, Stark SR, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA2007;297(13):1443-1454.

7. Burstein R, Collins B, Bajwa Z, et al. Triptan therapy can abort migraine attacks if given before the establishment or in the absence of cutaneous allodynia and central sensitization: clinical and preclinical evidence. Headache 2002, 42:390–391.

8. Burstein R, Yarnitsky D, Goor-Aryeh I, et al. An association between migraine and cutaneous allodynia. Ann Neurol2000;47(5):614-624.

9. Pr CAMBIA®. Product Monograph. Tribute Pharmaceuticals Canada Ltd. March 9, 2012.

10. Dahlöf C. Integrating the triptans into clinical practice. Curr Opin Neurol 2002;15:317-322.

Bibliography

11. Data on file, Nautilus Neurosciences.

12. Diener, HC, Montagna, P, Gács G, et al. Efficacy and Tolerability of Diclofenac Potassium Sachets in Migraine: A Randomized, Double-Blind,Cross-Over Study in Comparison with Diclofenac Potassium Tablets and Placebo. Cephalalgia 2006;26(5):537-47.

13. Dodick DW. Clinical clues and clinical rules: primary vs secondary headache. Adv Stud Med 2003;3:S550-S555.

14. Dodick DW, Capobianco DJ. Treatment and management of cluster headache. Curr Pain Headache Rep 2001;Feb;5(1):83-91Gladstone J and Dodick DW. Practical Neurology 2004;4:6-19.

15. Ferrari MD, Roon KI, Lipton RB et al. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001;358(9294):1668-75.

16. Gladstone J and Dodick DW. Practical Neurology 2004;4:6-19.

17. Graben RD, Maichle W. Pharmaceutical Formulation & Quality. Product Spotlight Dynamic Buffering Technology. September 2006:58-59.

18. Goadsby PJ. Re: Donnan GA, Davis SM 'Neurology: reflections on the past millennium as we enter the next. Journal of Clinical Neuroscience 2000;7:1-2. J Clin Neurosci 2000 Jul 7(4):377.

19. Haberer LJ, Walls, Lener, et al. Distinct pharmacokinetic profile and safety of a fixed-dose tablet of sumatriptan and naproxen sodium for the acute treatment of migraine. Headache 2010;50(3):357-373.

20. Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs.Arch Intern Med1999;159(8):813–818.

21. Idkaidek N and Arafat T. Effect of microgravity on the pharmacokinetics of Ibuprofen in humans.J Clin Pharmacol2011;51(12):1685-1689.

Bibliography

22. International Headache Society, 2nd edition. Cephalalgia 2004;24 Suppl 1:1-160.

23. Kahn K. Cambia® (diclofenac potassium for oral solution) in the management of acute migraine. US Neurology. 2011;7(2):139-143.

24. Kriegler JS. In: Tepper SJ and Tepper DE, eds. The Cleveland Clinic Manual of Headache Therapy. (New York, NY: Springer), 2011.

25. Krymchantowski AV, Filho PF, Bigal ME, et al. Rizatriptan vs. rizatriptan plus trimebutine for the acute treatment of migraine: a double-blind, randomized, cross-over, placebo-controlled study.Cephalalgia 2006;26(7):871-874.

26. Linde M. Migraine: a review and future directions for treatment. Acta Neurol Scand 2006;114(2):71–83.

27. Lipton RB, Diamond S, Reed M, et al. Migraine diagnosis and treatment: results from the American Migraine Study II. Headache 2001;41(7):638-645.

28. Lipton RB, Dodick D, Sadovsky R, et al. A self-administered screener for migraine in primary care: The ID Migraine validation study. Neurology 2003;61(3):375–382.

29. Lipton RB, Grosberg B, Singer RP, et al. Efficacy and tolerability of a new powdered formulation of diclofenac potassium for oral solution for the acute treatment of migraine: Results from the International Migraine Pain Assessment Clinical Trial (IMPACT), Cephalalgia 2010;30(11):1336-45.

30. Lipton RB, Stewart WF. Headache 1999;39 (Suppl 2):S20-S26.

31. Lipton RB, Stewart WF, Celentano DD, et al. Undiagnosed migraine headaches. A comparison of symptom-based and reported physician diagnosis. Arch Intern Med 1992;152(6):1273-1278.

32. Lipton RB, Stewart WF, Stone AM, et al. Stratified care vs step care strategies for migraine: the Disability in Strategies of Care (DISC) Study: A randomized trial. JAMA 2000;284(20):2599-2605.

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35. Pietrobon D. Migraine: new molecular mechanisms. Neuroscientist 2005;11(4):373–386.

36. Pryse-Phillips WEM, Dodick DW, Edmeads, JG et al. Guidelines for the diagnosis and management of migraine in clinical practice. Canadian Headache Society. Can Med Assoc J 1997; 156(9):1273-87.

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38. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; Sep 26;55(6):754-62.

39. Silberstein SD, Lipton RB, Dalessio DJ, Wolff’s Headache And Other Head Pain, Seventh Edition (New York: Oxford University Press Inc), 2001.

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The Art and Science of Evaluating and Treating Migraine

Additional Slides

Assessing Treatment Success

• Severity of disability (MIDAS or HIT-6)

• Duration, intensity, and frequency of attacks

• Use of medical resources:

Second dose

Rescue medication

Emergent care / clinic visits

• Incidence of adverse events

• Level of patient satisfaction

37. Silberstein SD. Neurology 2000; Sep 26;55(6):754-62.

32. Lipton RB, et al. JAMA 2000;284(20):2599-2605.

Recurrence

Return of episodic headache during the same attack

following acute treatment

• Prevention: Treat early, add NSAID

Use long-duration triptan or DHE

• Treatment: Repeat initial acute headache drug which is almost

always effective

43. Tfelt-Hansen P et al, Drugs. 2000; 60(6):1259-87

14. Dodick DW, Capobianco DJ Curr Pain Headache Rep 2001; Feb;5(1):83-91.

Rebound

Recurring headache induced by repetitive and

chronic overuse of acute headache medication

• Prevention: Limit frequency and dose of medications

• Treatment: Withdrawal and washout of overused medication;

consider using preventives

14. Dodick DW, Capobianco DJ Curr Pain Headache Rep 2001; Feb;5(1):83-91.

Mechanism of Cutaneous Allodynia

• Activation of the trigeminovascular system (TGVS) → release of

substance P, calcitonin gene-related peptide (CGRP), and

neurokinins by V (trigeminal) ganglion → neurogenic inflammation

in dura → vasodilatation of meningeal vessels, plasma

extravasation, and mast cell degranulation

• Neurogenic inflammation may activate/sensitize meningeal V

nociceptors

• Central sensitization occurs when there is sustained firing of

sensitized meningeal nociceptors → activation/sensitization of 2nd

order central trigeminovascular (TV) neurons → reduced pain

threshold and cutaneous allodynia

Non-pharmacological Therapies

Behavioural Treatments Include:

• Stress management / relaxation

training

• Regular diet and sleep

• Trigger identification and

avoidance

• Avoidance of excessive

over-the-counter medications

• Cognitive / behavioural

management therapy etc.

Physical Treatments Include:

• Natural remedies /

complementary medicines

• Acupuncture

• Transcutaneous electrical

nerve stimulation

• Occlusal adjustment

• Cervical manipulation

22. ICHD. Cephalalgia. 2004;24 Suppl 1:1-160