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

1
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
Migraine, Incidence
Female
?
Male
Incidents per 1000person-years
Age at Onset
Stewart et al Am J Epidemiol 1991
5

• Epidemiology Lesson 2
• Migraine is Very Prevalent

6
Prevalence in adults worldwide1-year prevalence
Population or community-based surveys of gt500
participants covering ages 25-60 y, using IHS or
modified IHS criteria
15.5
11.6
Lyngberg
13.2
Hagen
14.7
22.3
10.0
Dahlof
Patel
Roh
10.2
Rasmussen
14.7
8.4
23.2
11.7
Lampl
Sakai
OBrien
13.3
9.6
Launer
5.9
Stewart
Schwartz
Bank
14.3
Takeshima
14.0
12.2
16.7
Steiner
Stewart
7.7
Lipton
Zivadinov
8.5
11.6
Wang
8.5
Kryst
9.0
Lipton
13.5
3.0
Morillo
Alders
Miranda
10.1
12.6
10.0
Tekle Haimanot
5.0
9.3
Deleu
Morillo
Morillo
16.3
Dent
Morillo
8.2
Wiehe
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)
Morillo
5.3
Jaillard
7.3
Mean 11.2 Median 10.2
5.0
Lavados
Morillo
Steiner TJ. Lifting the burden The global
campaign against headache. Lancet Neurol
20043(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 200768(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 200141(7)646-657.
10

• Epidemiology Lesson 4
• The Burden of Migraine is Severe and Complex

11
Burdens of One Persons Migraine
lifestyle compromise
patienthood
pain and suffering
personal financial costs
anxiety
co-morbidity
employer work colleagues
family burden
societal burden
12
The Several Burdens of Migraine

• 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

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
20043(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 Sufferers Partner
USA and UK populations (245 migraine sufferers,
100 partners)
Lipton et al. Cephalalgia 200323429-440
16
The Economic Burden of Migraine - Migraine is
Costly to Society
Annual Cost in the US? 14.5 Billion Annually
(1998)
Missed Work
10
7.9B
30
Direct Medical Cost
1.2B
60
5.4B
Reduced Productivity
Hu H et al. Arch Intern Med. 1999159813-818.
17

• Epidemiology Lesson 5 There Are Several Barriers
  Preventing Good Outcomes in Migraine Treatment

18
Barriers to Successful Outcomes
Lipton RB et al. Neurology. 1994.
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 200747 Suppl
1S2-9.
20
Most People With Migraine Still Use OTC
Medications
6 in 10 Sufferers Still Rely on OTCs Alone or No
Medication to Manage Headache Pain
Lipton RB et al. Headache. 200141638-645.
21
Among Individuals Who Receive Therapy,
Maintanaince is Low
Determinant Relevance Potential Modifiable Factors (hypotheses) Potential Actions
Disease's Driven This determinant works as an "umbrella" factor. If the disease is seen as trivial, patients may be less motivated to use meds. Accordingly, understanding this component will drive all the other determinants. Neutralizing concepts such as 1) Migraine is not lethal 2) Migraine is another annoying part of life that I have to deal with. 3) Migraine has nothing to do with the brain. 4) Migraine may be treated with OTCs and analgesics (see link with medication overuse project). Awareness campaigns focusing on 1) Nobody should live with pain. 2) There are consequences of poor management (e.g migraine progression) 3) Migraine is a disorder of the brain 4a) There are medications that target the very biology of migraine 4b) Medication overuse is a consequence of migraine mismanagement.
Medication's driven Understanding factors associated with satisfaction/dissatisfaction after using specific meds over the long haul increase maintenance of therapy strategies. Why are the determinants of low maintenance to therapy? Adverse events? Formulary restrictions? Fear (perception of safety)? Based on findings, to build awareness campaigns accounting for the fear factor, limited formulary and limited knowledge of disease
Physician's Driven Some doctors are more efficient than others in engaging patients. Why? 1) Do they request follow up visits? 2) Do they explain more about the disease? 3) Are they less focused on rare side effects? 1 )Education activities that focus on health provider's actions that are associated with satisfaction and adherence.
Patient's driven What factors are associated with the decision making process about using meds? And being actively engaged with the plan? 1) Lack of disease-specific knowledge may be associated with poor adherence and MDs have little time to educate patients. 2) Comorbidities (anxiety, depression) may interfere in adherence. Unrealistic expectations may impact adherence Patient-centered education activities (tapes, web-based, short education activities) may increase adherence in a cost effective way.
22

• Epidemiology Lesson 6 Comorbidities are Frequent
  in Migraine and Complicate Diagnosis and Treatment

23
Migraine is Comorbid With

• Neurologic disorders
• Epilepsy
• Ischemic stroke
• Tourettes
• Psychiatric disorders
• Depression
• Bipolar disease
• Anxiety/panic disorder

• Other disorders
• Raynauds
• Snoring/sleep apnea
• Asthma/allergy
• Noncephalic pain
• GI disorders
• Arthritis
• Low back pain

24
Comorbidities Increase With Increased Headache
Frequency

OR2.1 (1.7 2.5)



OR1.8 (1.5 2.2)

OR1.6 (1.1 2.4)


OR1.7 (1.4 2.1)


OR2.5 (2.1 3.02)

ORs and 95 confidence intervals adjusted for
age, gender and SES (income)
25

• Epidemiology Lesson 7
• Although the Prognosis of Migraine is Variable,
  in a Subgroup Migraine Progresses Into Chronic
  Migraine

26
Migraine
Bigal ME, Lipton RB. The prognosis of migraine.
Curr Opin Neurol 200821(3)301-308.
27
Evidence from Epidemiology
28
Risk Factors for Migraine Progression
Not modifiable by health interventions FemaleSex L
ow 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-Inflammat
ory Status Pro-Thrombotic Status
Bigal and Lipton, Headache 2006
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
200848(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
200848(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.