Migraine in the 21st Century:

Lessons from Epidemiologic Studies

Marcelo E. Bigal, M.D.; Ph.D.

Global Director for Scientific Affairs ─Neuroscience Merck Research Laboratories

Dept of Neurology, Albert Einstein College of Medicine

2

Overview

To review the epidemiology of migraine. Is migraine worth attention?

To review the burden of migraine on the individual, family and society. Is migraine worth recognition?

To estimate patterns of diagnosis and treatment for migraine, as well as barriers for care

To discuss the prognosis of migraine

3

Epidemiology Lesson 1

Migraine peaks with incidents in the teens and early twenties

Accordingly, first migraine attacks often happen in childhood or

puberty

4

Incidents per 1000

person-years

Age at Onset

Stewart et al: Am J Epidemiol 1991

FemaleMale

30

25

20

15

10

5

00 5 10 15 20 25 30

Migraine, Incidence

5

Epidemiology Lesson 2

Migraine is Very Prevalent

6

14.7

Prevalence in adults worldwide:1-year prevalence

11.7

14.0

13.3

12.2

11.6

3.0

5.0

8.5

11.6

13.210.0

10.2

9.6

16.7

23.2

14.3

Population or community-based surveys of >500 participants covering ages 25-60 y,

using IHS or modified IHS criteria

Africa 4.0 (2 studies)

Asia 10.6 (6 studies)

Australia

Europe 13.8 (9 studies)

N. America 12.6 (8 studies)

S. America 9.6 (10 studies)

8.4

5.9

22.3

9.0

10.1

7.7

5.3

5.0

16.3

12.6

9.3

8.2

10.0

8.5

7.3

13.5

Tekle Haimanot

Dent

Sakai

Takeshima

Roh

Alders

Deleu

Wang

Lampl

Zivadinov

Rasmussen

Bank

Launer

Hagen

Dahlof

Steiner

Kryst

Schwartz

O’Brien

Stewart

StewartLipton

Lipton

Jaillard

Morillo

Wiehe

Morillo

Morillo

Morillo

Morillo

Morillo

Miranda

Lavados

15.5Lyngberg

14.7Patel

Mean: 11.2

Median: 10.2

Steiner TJ. Lifting the burden: The global campaign against headache. Lancet Neurol 2004;3(4):204-205.

7

Epidemiology Lesson 3

In the US migraine affects over 12% of the adults

Migraine is the most common neurological disease in men (6%)

Migraine is 3 times more common in women (18%) P

Prelavence peaks in adulthood, coinciding with the peak of work productivity

8

Migraine is very common in US. Results of 3 large studies conducted 15 years apart

Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007;68(5):343-349.

9

Migraine is Most Common in Women and During Peak Productive Years

Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 2001;41(7):646-657.

10

Epidemiology Lesson 4

The Burden of Migraine is Severe and Complex

11

pain and suffering

Burdens of One Person’s Migraine

anxiety

patienthood

personal financial costs

employer& work

colleagues

lifestyle compromise

societal burdenfamily burden

co-morbidity

The burden of migraine is severe and affects:

Burden on Individual: – Health-related quality of life– Disability– Interictal burden of migraine

Burden on the family:– Migraine affects relationships

• Burden on society:– Costs

The Several Burdens of Migraine

13

Burden on the Individual - Leading Causes of Years of Life Lost to Disability (YLDs) – WHO Report

Steiner TJ. Lifting the burden: The global campaign against headache. Lancet Neurol 2004;3(4):204-205.

14

The Burden of Migraine is Not Restricted to the Attack – The Interictal Burden

Symptom Burdens

During attacks– pain and suffering, leading to– reduced functional ability

Beyond the attack– fear of the next attack, leading to– avoidance behaviour and

lifestyle compromise

15

The Family Impact of Migraine – Migraine Damages Relationships With Sufferer’s Partner

36%36%

20%20%

From their partners’ perspective

56%56%

35%35%

29%29%

USA and UK populations (245 migraine sufferers, 100 partners)

From the sufferers’ perspective

56%56%Spend less time with partnerSpend less time with partner

50%50%More likely to argueMore likely to argue

47%47%Be a better partnerBe a better partnerwithout headacheswithout headaches

60%60%Less involved withLess involved withpartner at homepartner at home

% Sufferers affected

0 20 40 60 80

73%73%Less able to communicateLess able to communicate

100

Lipton et al. Cephalalgia 2003;23:429-440

16

The Economic Burden of Migraine - Migraine is Costly to Society

Annual Cost in the US $14.5 Billion Annually (1998)

Hu H et al. Arch Intern Med. 1999;159:813-818.

$7.9B$7.9B

$5.4B$5.4B

$1.2B$1.2B

10%10%

30%30%

60%60%

EmergencyRoom, Other

Rx

Office Visits

Missed Work

Direct Direct Medical Medical CostCost

Reduced Productivity

17

Epidemiology Lesson 5: There Are Several Barriers

Preventing Good Outcomes in Migraine Treatment

18

EncourageFollow-Up

ImproveTreatment

ImproveDiagnosis

Barriers to Successful Outcomes

Lipton RB et al. Neurology. 1994.

Motivate Patientsto Seek Care

19

Although Progresses Were Made, a Significant Proportion of Migraineurs are Unaware of Their Diagnosis

AMS-I AMS-II AMPP Change of 15 years

Migraine Diagnosis 38% 48% 56.20% 47.9%

Sinus Diagnosis 43.10% 42% 39% -9.5%

Tension Headache 44% 32.30% 31% -29.5%

"Sick" headaches 13.10% 7.80% 7.50% -42.7%

Cluster headache 17.90% 6.50% 9.90% -44.7%

Lipton RB, Bigal ME. Ten lessons on the epidemiology of migraine. Headache 2007;47 Suppl 1:S2-9.

20

Most People With Migraine Still Use OTC Medications

1999

57%

41%

2%

None

Any Rx

OTCOnly

1989

59%

37%

4%

6 in 10 Sufferers Still Rely on OTCs Alone or No Medication to Manage Headache Pain

Lipton RB et al. Headache. 2001;41:638-645.

22

Epidemiology Lesson 6: Comorbidities are Frequent in

Migraine and Complicate Diagnosis and Treatment

23

Migraine is Comorbid With:

Neurologic disorders– Epilepsy– Ischemic stroke– Tourette’s

Psychiatric disorders– Depression– Bipolar disease– Anxiety/panic disorder

Other disorders– Raynaud’s– Snoring/sleep apnea– Asthma/allergy– Noncephalic pain– GI disorders– Arthritis– Low back pain

24

Comorbidities Increase With Increased Headache Frequency

15

22

3

19

26

31

34

5

30

41

0 5 10 15 20 25 30 35 40 45

Chronic Pain

Arthritis

Bipolar

Anxiety

Depression (PHQ-9)

EM CM

OR=2.1 (1.7 – 2.5)*%

%

%%

* ORs and 95% confidence intervals adjusted for age, gender and SES (income)

%

%%

%%

%

OR=1.8 (1.5 – 2.2)*

OR=1.6 (1.1 – 2.4)*

OR=1.7 (1.4 – 2.1)*

OR=2.5 (2.1 – 3.02)*

25

Epidemiology Lesson 7

Although the Prognosis of Migraine is Variable, in a

Subgroup Migraine Progresses Into Chronic Migraine

04/18/23

Migraine

RemissionEvolution to symptom free

over prolonged period of time

PersistenceRelative clinical stability and no markers of progression

Progression

Clinical- Evolution to chronic migraineFunctional- Changes in the PAG- Central sensitizationAnatomical- Lesions in the brain- Lesions outside the brain

Bigal ME, Lipton RB. The prognosis of migraine. Curr Opin Neurol 2008;21(3):301-308.

27

Evidence from Epidemiology

Baseline 1-year follow-up

798 Migraineurs

Stable controls(2 to 104 headache days/year)

Intermediate(105 to 179 headache days/year)

New-onset CDH (180+ headache days/year)

23 (3%)

49 (6%)

726 (91%)

Scher AI et al. Pain. 2003;16:81-89.

28

Risk Factors for Migraine Progression

Bigal and Lipton, Headache 2006

Not modifiable by health interventions

FemaleSex

Low Socioeconomic Status

Head Trauma

Modifiable by health interventions

Attack Frequency

Obesity

Medication Overuse

Caffeine Overuse

Stressful life events

Snoring

Other

Allodynia

Other pain syndromes

Pro-Inflammatory Status

Pro-Thrombotic Status

29

Probability of Chronic Migraine as a Function of Barbiturate Exposure

Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache 2008;48(8):1157-1168.

30

Probability of Chronic Migraine as a Function of Opioid Exposure

Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache 2008;48(8):1157-1168.

31

Summary

Migraine is a frequent and disabling chronic disease with recurrent attacks

Migraine is common in men and 3 times more common in women

The burden of migraine is higher in the years of peak productivity

The burden of migraine affects the individual, family and society

32

Summary

Despite improvements, several barriers to good migraine outcomes still exist

Several disorders are comorbid to migraine. They complicate diagnosis and treatment

In a subgroup, migraine progresses. Risk factors for progression have been identified and should be screened and treated.