1. Burden of Illness
Welcome to this presentation in the series “Know Migraine Pain.” In this module, we will discuss the burden of illness caused by migraine pain.

2. PATIENT BURDEN OF MIGRAINE
In the first part of the talk we’ll discuss the patient burden of migraine.

3. Impact of Migraine
Let’s start with the impact of migraine.

4. Impact of Migraine
Migraine accounts for 1.3% of years lost to disability2
Burden on sufferers2
Personal suffering
Impaired quality of life
Financial cost
Constant fear of another headache
Damage family and social life and employment
Migraine has a substantial socioeconomic impact. It accounts for 1.3 of years lost to disability. The burden on people suffering from migraine is caused by a variety of factors, including personal suffering, impaired quality of life, financial cost, the constant fear of another headache, as well as the damage family and social life and employment. Finally, depression is three times more common in people who suffer migraines or severe headaches than in healthy individuals.
Depression is three times more common in people who suffer migraines or severe headaches than in healthy individuals2
1. Smitherman TA et al. Headache. 2013;53(3):
2. WHO Headache disorders. Available at:

5. Impact of Migraine
About 50% of migraine sufferers are severely disabled or require bed rest
Some disability is due to comorbid conditions
Financial cost of headache arises partly from direct treatment costs, but much more from loss of work time and productivity
Annual U.S. direct medical costs attributable to migraine were estimated at $1 billion in 1999
In 2004, the total cost of migraine in the EC (15 countries) was estimated at €25 billion per year, the next-highest after dementia among neurological disorders
Continuing the discussion of the impact of migraine, about 50% of migraine sufferers are severely disabled or require bed rest, although some of this disability is due to comorbid conditions. The financial cost of headache arises partly from direct treatment costs, but a much greater cost comes from loss of work time and productivity. The annual U.S. direct medical costs attributable to migraine were estimated at $1 billion in 1999, and in 2004, the total cost of migraine in the EC (15 countries) was estimated at €25 billion per year, which makes the cost for migraine the next-highest after dementia among neurological disorders. For comparison, migraine reduces health-related quality of life more than osteoarthritis or diabetes.
Migraine reduces health-related quality of life more than osteoarthritis or diabetes
IASP Fact Sheet – Epidemiology of Headache 2012

6. Migraine Patients Experience Severe Pain and Disability
These two pie charts give an overview of the degree of pain, shown on the left, and disability, shown on the right, that migraine patients experience.
Pain
Disability
American Headache Society. Brainstorm Available at: Accessed 04 December, 2014.

7. Impact of Migraine on Patient’s Daily Lives
This slide quantifies the impact of migraine on the patient’s daily lives. Seventy-six percent of migraine patients are unable to do chores or housework, 67% are experience a greater than 50% reduction in the productivity of their household work, 59% of patients miss family, social or leisure activities due to migraine, and 51% see greater than 50% reductions of the productivity of their work or school productivity.
Lipton RB et al. Headache. 2001;41(7):

8. This slide gives a breakdown of somatic symptoms in women by headache frequency and headache-related disability. Please take a moment to review.

9. Impact of Chronic Migraine on Daily Activities over a 3-Month Period
This slide gives a breakdown of the impact of chronic migraine on daily activities over a 3 month period. Please take a moment to review.
Bigal M et al. Headache. 2009;49(7):

10. Social and Economic Burden of Headache Disorders
Large amount of disability and financial costs to society
Most troublesome during people’s productive years
25 million working/school days lost annually in the UK due to migraine
Cost is matched by tension-type headache and chronic daily headache combined1
Many do not receive effective care1
Only 50% of those with migraine consult a physician
Only two-thirds are correctly diagnosed1
This slide summarizes the social and economic burden due to headache disorders. Headache disorders cause a large amount of disability and financial costs to society. They are most troublesome during people’s productive years . For instance, 25 million working/school days lost annually in the UK due to migraine. Many of the patients with migraine do not receive effective care. Only 50% of those with migraine consult a physician, and of these only two-thirds are correctly diagnosed.
1. WHO Headache disorders. Available at:

11. Psychosocial Burden of Migraine
Problems are commonly reported with:
Energy and drive function
Emotional functions
Sensation of pain
Remunerative employment
General evaluations of mental and physical health
Social function
Global disability evaluations
Beyond its socioeconomic impact, migraine is also associated with a psychosocial burden. Commonly reported psychosocial problems include energy and drive function, emotional function, the sensation of pain, remunerative employment, general evaluations of mental and physical health, social function, and global disability evaluations. However, symptomatic and prophylactic treatments, can reduce patient difficulties and the associated burden of migraine
Symptomatic and prophylactic treatments can reduce patient difficulties and the associated burden of migraine
Raggi A, Giovannetti AM, Quintas R et al. J Headache Pain. 2012;13(8):

12. Comorbidities of Migraine
In this section of the presentation we’ll consider the comorbidities of migraine.

13. Comorbidities of Migraine
Strong association with
Anxiety and mood disorders
Allergies
Chronic pain disorders
Epilepsy
Migraine with aura is a risk factor for ischemic stroke and silent brain lesions on MRI, particularly in women with frequent attacks
Migraine is strongly associated with a number of comorbidities, including anxiety and mood disorders, allergies, chronic pain disorders, and epilepsy. Moreover, migraine with aura is a risk factor for ischemic stroke and silent brain lesions on MRI, particularly in women with frequent attacks.
IASP Fact Sheet – Epidemiology of Headache 2012

14. Prevalence of Anxiety and Depression in Patients with Migraine*
This slide shows a quantitative representation of the overlap between populations suffering from migraine, anxiety and depression. Note that approximately 1/3 of migraine sufferers with anxiety had depression, and approximately 2/3 of migraine sufferers with depression had anxiety.
Approximately 1/3 of migraine sufferers with anxiety had depression
Approximately 2/3 of migraine sufferers with depression had anxiety
*Numbers of patients
Oh K et al. BMC Neurol. 2014;14(1):238.

15. Anxiety and Depression Influence Frequency of Migraine Attacks
This slide gives a breakdown of the frequency of headaches per month, the VAS score for pain intensity, and the HIT-6 score by migraine comorbidity. Please take a moment to review, particularly the numbers for patients with the double comorbidity of anxiety and depression, framed in red on the right.
Combination of anxiety and depression increases headache frequency
Anxiety increases headache intensity
Oh K et al. BMC Neurol. 2014;14(1):238.

16. Anxiety and Depression Influence Migraine-Induced Disability
This slide shows the correlation between migraine disability assessment (MIDAS) grade and comorbidities. Note that the proportion of patients with both anxiety and depression increased significantly with increasing MIDAS grade. Therefore, anxiety and depression should be systematically looked and cared for in patients with migraine.
Anxiety and depression should be systematically looked for and cared for in patients with migraine
MIDAS = Migraine-related Disability
Lantéri-Minet M et al. Pain. 2005;118(3):

17. Migraine and Depression
Migraine associated with depression, anxiety, phobias, and panic disorders
Migraine with aura: higher lifetime prevalence of major depressive disorder than patients with migraine without aura
Possible mechanisms:
Psychiatric disorders and migraine are associated as a result of chance
Migraine is a causal factor in the development of psychiatric conditions or vice versa – or both
Shared environmental risks for depression and migraine may exist
A common shared etiological factor may explain the coexistence of depression and migraine
Lets explore the relationship between Migraine and depression. Migraine with aura is associated with a higher lifetime prevalence of major depressive disorder than patients with migraine without aura. This association may be due to a chance association of psychiatric disorders and migraine. Conversely, migraine may be causal factor in the development of psychiatric conditions or vice versa – or both. Shared environmental risks for depression and migraine may exist, and finally, a common shared etiological factor may explain the coexistence of depression and migraine.
Frediani F, Villani V. Migraine and depression. Neurol Sci. 2007;28 Suppl 2:S161-5.

18. Migraine and Depression: A Bidirectional Relationship with Common Neurobiology
Monoamine and peptide transmitters may be involved in depression
Endorphins and encephalins are involved in mood and pain control
Serotonin has been implicated in migraine, and tension-type headache
Also implicated in mood disorders, anxiety disorders, sleep disorders, eating disorders, and obsessive-compulsive behavior
Evidence suggests dopamine is involved in migraine
Migraine prodrome often characterised by dopaminergic symptoms
Anti-dopaminergic drugs can often be helpful in treating migraine
Migraine and depression share a bidirectional relationship with common neurobiology. Specifically, monoamine and peptide transmitters may be involved in depression, and endorphins and encephalins are involved in mood and pain control. Serotonin has been implicated in migraine, and tension-type headache, and it is also implicated in mood, anxiety, sleep, eating and disorders, as well as in obsessive-compulsive behavior. Dopamine may also be involved in the pathophysiology. Specifically, the migraine prodrome often characterised by dopaminergic symptoms, and anti-dopaminergic drugs can often be helpful in treating migraine. Thus, severe headache, severe somatic symptoms, and major depression may be linked through dysfunction of the serotonergic and dopaminergic systems.
Severe headache, severe somatic symptoms, and major depression may be linked through dysfunction of the serotonergic and dopaminergic systems
Frediani F, Villani V. Migraine and depression. Neurol Sci. 2007;28 Suppl 2:S161-5.

19. Migraine, Depression, and Quality of Life
Depression or anxiety are not determined by migraine intensity
Significant association between migraine frequency and depression
Significant association between depression and duration of migraine attacks
Migraine and depression significantly decrease HRQoL
Patients with migraine may have a lower HRQoL even after controlling for depression
More frequent attacks = poorer quality of life
Lets have a look at the interaction between migraine, depression and the quality of life. Depression or anxiety are not determined by migraine intensity. However, there is a significant association between migraine frequency and depression, as well as a significant association between depression and duration of migraine attacks. Migraine and depression both significantly decrease health related quality of life, so that patients with migraine may have a lower health related quality of life even after controlling for depression. It is important to keep in mind that more frequent attacks equal a poorer quality of life.
HRQoL = health-related quality of life
Frediani F, Villani V. Migraine and depression. Neurol Sci. 2007;28 Suppl 2:S161-5.

20. Effect of Migraine on Sleep Quality
This slide gives a breakdown of the Pittsburgh Sleep Quality Index or PSQI as it related to migraine. The PSQI score total score was highest in patients with frequent migraine and lowest in controls. Significant differences exist between migraine sufferers and controls in four sub-scores of the PSQI, indicating that decreased quality of sleep is a consequence of migraine itself and cannot be explained exclusively by comorbid depression or anxiety.
PSQI score total score highest in patients with frequent migraine and lowest in controls
 sleep quality is due to migraine; cannot be explained exclusively by comorbid depression or anxiety
Seidel S et al. Cephalalgia. 2009;29(6):662-9.

21. Effect of Migraine on Fatigue
This slide summarizes the relationship between migraine and fatigue. Elevated depression and/or anxiety and indicated by self-rated depression (SDS) and self-rated anxiety (SAS) scores decreased significantly for patients with fewer than 8 migraine days/month. Fatigue and daytime sleepiness did not differ between migraine suffers and control subjects.
Prevalence of depression and/or anxiety and SDS and SAS scores decreased significantly from patients with ≥8 migraine days/month
Fatigue and daytime sleepiness did not differ between migraine suffers and control subjects
Seidel S et al. Cephalalgia. 2009;29(6):662-9.

22. Migraine and Other Comorbidities
Low back pain
Allergies
Irritable bowel syndrome
Migraine may also be associated with a number of other comorbidities, including low back pain, allergies, irritable bowel syndrome, and fibromyalgia.
Fibromyalgia
Yoon MS, Manack A, Schramm S et al. Pain. 2013;154:

23. Obesity increases migraine frequency
Migraine and Obesity
Body Weight
Risk of CM
Normal 3%
Overweight 9%
Obese
15%
The table on the right illustrates the relationship between chronic migraine and body weight. Obesity does not cause migraines but rather promote their frequency. Normal weight individuals with migraine have about a 3% chance of developing chronic headaches in a year. In overweight individuals, this risk is three times higher, and in obese individuals it is increased five times relative to normal weight individuals with migraine.
Obesity increases migraine frequency
Tepper DE. Headache: The Journal of Head and Face Pain. 2013;53:71920.

24. Migraine and Vascular Disease
Migraine associated with increased cardiovascular or cerebrovascular disease
Migraine with aura increases risk of myocardial infarction and ischemic stroke
Migraine without aura raises both risks by approximately 25%
Migraines during pregnancy linked to stroke and vascular diseases
Migraine with aura for women in midlife associated with late-life vascular disease (infarcts) in the cerebellum
Male and female migraine sufferers have a 2.5-fold increased risk of subclinical cerebellar stroke
Aura + increased headache frequency = highest risk
Migraine associated with higher incidence of adverse cardiovascular profiles, including diabetes and hypertension
Migraine is associated with increased cardiovascular or cerebrovascular disease. Migraine with aura increases risk of both myocardial infarction and ischemic stroke. Migraine without aura raises both risks by approximately 25%, migraines during pregnancy linked to stroke and vascular diseases, and migraine with aura for women in midlife is associated with late-life vascular disease in the cerebellum. Both male and female migraine sufferers have a 2.5-fold increased risk of subclinical cerebellar stroke. Therefore it is important to remember that aura plus increased headache frequency equal highest risk, and that migraine is associated with a higher incidence of adverse cardiovascular profiles, including diabetes and hypertension.
Chawla J Available at Accessed 05 January 2014.

25. Medication Overuse Headache (MOH)
New or worsening of existing headache develops in association with medication overuse
Headache on ≥15 days/month for >3 months due to overuse of acute medications
About 50% of people have MOH
Most patients improve after withdrawal of the overused medication
New or worsening of existing headache develops in association with medication overuse, and the mechanism underlying this phenomenon are shown on the figure below. Headache on 15 days/month or more for more than 3 months may be due to overuse of acute medications. About 50% of people have medication overuse headache, but most patients improve after withdrawal of the overused medication.
Headache Classification Committee of the International Headache Society (IHS). Cephalalgia. 2013;33(9):

26. If Migraine Is NOT Treated Effectively…
It may cause severe suffering, loss of quality of life, loss of productivity, have economic considerations
Patient may develop chronic migraine or medication overuse headache
Finally lets consider what may happen if migraine is not treated effectively. Firstly, migraine may cause severe suffering, loss of quality of life, loss of productivity, and it may have economic consequences. Secondly, patients may develop chronic migraine or medication overuse headache.

27. Literature Cited
American Headache Society. (2004). Brainstorm. Retrieved June 18, 2015, from Bigal, M., Krymchantowski, A. V., & Lipton, R. B. (2009). Barriers to satisfactory migraine outcomes. What have we learned, where do we stand? Headache, 49(7), 1028– Frediani, F., & Villani, V. (2007). Migraine and depression. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 28 Suppl 2, S161– iasp-pain.org. (2012). Epidemiology of headache. Retrieved June 18, 2015, from (IHS, H. C. C. of the I. H. S. (2013). The international classification of headache disorders, (beta version). Cephalalgia, 33(9), 629–808. Lantéri-Minet, M., Radat, F., Chautard, M.-H., & Lucas, C. (2005). Anxiety and depression associated with migraine: influence on migraine subjects’ disability and quality of life, and acute migraine management. Pain, 118(3), 319–326.

28. Literature Cited (Continued)
Lipton, R. B., Stewart, W. F., Diamond, S., Diamond, M. L., & Reed, M. (2001). Prevalence and Burden of Migraine in the United States: Data From the American Migraine Study II. Headache: The Journal of Head and Face Pain, 41(7), 646– Migraine Headache: Practice Essentials, Background, Pathophysiology. (2015). Retrieved from Oh, K., Cho, S.-J., Chung, Y. K., Kim, J.-M., & Chu, M. K. (2014). Combination of anxiety and depression is associated with an increased headache frequency in migraineurs: a population-based study. BMC Neurology, 14(1), Raggi, A., Giovannetti, A. M., Quintas, R., D’Amico, D., Cieza, A., Sabariego, C., … Leonardi, M. (2012). A systematic review of the psychosocial difficulties relevant to patients with migraine. The Journal of Headache and Pain, 13(8), 595– Seidel, S., Hartl, T., Weber, M., Matterey, S., Paul, A., Riederer, F., … PAMINA Study Group. (2009). Quality of sleep, fatigue and daytime sleepiness in migraine - a controlled study. Cephalalgia: An International Journal of Headache, 29(6), 662–669.

29. Literature Cited (Continued 2)
Smitherman, T. A., Burch, R., Sheikh, H., & Loder, E. (2013). The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache, 53(3), 427– WHO | Headache disorders. (n.d.). Retrieved June 18, 2015, from Yoon, M.-S., Manack, A., Schramm, S., Fritsche, G., Obermann, M., Diener, H.-C., … Katsarava, Z. (2013). Chronic migraine and chronic tension-type headache are associated with concomitant low back pain: results of the German Headache Consortium study. Pain, 154(3), 484–492.