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Non-pharmacological and pharmacological prevention of episodic migraine and chronic daily headache.


Migraine is the most common moderate to severe headache disorder worldwide, disproportionately affecting women, and causing significant healthcare utilization. Annual costs of migraine disorders, including medication, provider visits, emergency room utilization, absenteeism, and loss of productivity, have been estimated at $13 billion dollars annually in the United States. (1) This number does not include the treatment of other co-morbid and/ or secondary conditions such as depression, anxiety, and renal disease secondary to excessive NSAID use. Risk factors for migraine include obesity and low socioeconomic status, thus leading to an even greater burden in West Virginia. West Virginia had the nation's largest increase in drug mortality overdoses in 1999 to 2004, with 93% of the decedents taking opioid analgesics. (2)

The one-year prevalence of migraine ranges from 0.7% to 16.1% for men and 3.3% to 32.6% for women. Women have a lifetime prevalence three times greater than men, with 18% of women experiencing migraine compared to 6% of men. (3) The significantly higher prevalence of migraine disorders in women further fuels the rising costs of migraine in the United States, as women continue to become increasingly represented in the workforce.

Unfortunately, despite the significant personal, social, and societal impact of migraine, pharmacologic treatment options have remained limited in number and effect. NIH funding for migraine research has been nearly nonexistent, and the burden of drug discovery has been left entirely to the pharmaceutical industry. We will discuss the advances in this area later, but the focus of this report is the non-pharmacologic prevention of episodic migraine headache and tools to avoid the progression to chronic migraine.

Prevention of Episodic Migraine

Episodic migraine is thought to be a genetic condition, and therefore, there is no true method of preventing its development in a predisposed individual. However, prevention of migraine in frequency and severity, and therefore in disability and impact, is well proven and multifaceted. Prevention includes lifestyle modification, trigger avoidance, non-pharmacological interventions, treatment of comorbidities, and pharmacotherapy. It is the responsibility of the medical provider to be as informed about all means of migraine prevention as he/ she is about preventive medications.

Lifestyle modification is an often overlooked, under-utilized tool in the prevention of episodic migraine. In general, healthy lifestyle choices are also helpful for migraine. Two important areas of possible intervention include sleep hygiene and exercise. Lack of quality sleep, whether from inadequate time in bed, inconsistent bedtimes, sleep cycle disruption from medications, or obstructive sleep apnea, can greatly increase the susceptibility to develop migraine. Providers need to stress the importance of regular sleep schedules including set bedtimes and waking times, avoidance of caffeine especially in the afternoon and evening, and limited use of benzodiazepines which disrupt sleep architecture. Patients should be encouraged to avoid taking work or stress to bed, watching television or doing computer work in bed. Any patient with complaints of daytime sleepiness, morning headaches, or obesity should be screened for obstructive sleep apnea. Exercise of 40 minutes three times per week was recently shown to be as effective in preventing migraine as topiramate. (4)

Migraine triggers are wide ranging and variable between patients. Common triggers include dietary triggers, hormonal fluctuations, dehydration, fluorescent and strobe lighting, sleep disruptions, stress, and weather changes. Many of these triggers can be avoided or minimized, especially dietary triggers. Although there are a multitude of dietary triggers which have been reported, the more common ones include monosodium glutamate

(MSG), nitrates, and red wine. MSG is present in many snack foods such as potato chips as well as in canned soups. Nitrates are used as preservatives in many processed meats, such as prepackaged deli meat, hotdogs, bacon, and sausage. It is nearly impossible for patients to avoid all dietary triggers all the time, but it is important that they try to limit their exposure. It is also important for patients to keep headache and dietary calendars, at least temporarily, and for providers to review these with patients to look for other potential triggers which could be avoided. There are many "migraine diets" available on the internet, but many of these are overly inclusive of all reported dietary triggers and may lead to avoidance of foods which are not triggers of the individual patient.

Other triggers are more difficult to avoid (hormonal therapy in estrogen induced migraine is beyond the scope of this article), but patients who are aware of their triggers can prepare more adequately by ensuring appropriate sleep, good hydration, and even closer monitoring of dietary limitations.

Non-pharmacologic approaches in the prevention of migraine include biofeedback and cognitive behavioral therapy, as well as other less well proven but promising therapies including relaxation therapy, massage, acupuncture, and other physical therapies. Biofeedback training is a technique where patients become aware of physiologic processes such as heart rate and breathing and learn to exert a level of control of them. Biofeedback has been shown to significantly decrease the frequency of migraine attacks. (5) Cognitive Behavioral Therapy (CBT) has also been shown to be effective in preventing migraine headaches. (6) CBT deals primarily with stress management and identifying/ treating common co-morbidities with migraine such as mood and sleep disorders. These methods return control to the patient by helping patients recognize how decisions and approaches will affect the severity and frequency of migraine, which has shown improvement in quality of life scores. (7)

Lastly, pharmacologic treatment to prevent episodic migraine may be warranted. Many patients who suffer from migraine and should be treated are not on preventive medication. The American Migraine Prevalence and Prevention (AMPP) trial revealed that approximately 40% of participants may have benefited from preventive therapies but were not receiving it. (8) The FDA has approved only four medications for the prevention of migraine: propranolol, timolol, valproate, and topiramate. Propranolol is often started at relatively low doses, such as 20mg bid, but often requires titration up to 120-240mg per day in divided doses. Timolol doses range from 20-60mg daily in divided doses. It is important to remember that asthma and depression can be aggravated by the use of beta-blockers, so care must be taken to monitor for side effects. Valproate is commonly initiated at 125-250mg bid and then titrated to 1000-1500mg daily. Weight gain and hair loss are potentially troublesome side effects, and great caution is required to prevent its use during pregnancy. Valproate can affect neural tube development, which occurs early during pregnancy, often even before the patient knows that they are pregnant. Topiramate has shown efficacy in migraine prevention in doses ranging from 100-200mg in divided doses, although it can be given once daily for improved compliance or to reduce daytime side effects. It should be initiated at 25mg per day and then titrated upward slowly to minimize paresthesias. Other potential side effects include appetite suppression and changes in taste (especially carbonated beverages) and cognitive changes. Other commonly used preventive agents include atenolol, nadolol, verapamil, amitriptyline and gabapentin. (9) There are a few "natural" supplements which have sufficient evidence to consider for prevention of episodic migraine, including magnesium, (10) riboflavin, coenzyme Q10, and butterbur (butterbur 75 mg BID has been shown to decrease migraine frequency). (11) It is important to remember that most of the commonly used preventive medications work to reduce headache frequency by 50% in 50% of patients. Therefore, patients are likely to continue to have some migraines requiring abortive therapy.

Prevention of Chronic Daily Headache

Chronic Daily Headache (> 15 days per month of headache) is present in up to 4% of the adult population. Most of the patients with Chronic Daily Headache (CDH) began with episodic headaches and progressed to CDH over time. CDH affects women twice as often as men. In a one-year study of episodic migraine subjects, 2.5% developed chronic migraine by the end of the year. (12) There are a number of risk factors associated with progression to CDH, and it is the modifiable risk factors which will be addressed further. Risk factors for progression to CDH include lower socioeconomic status, not being married, obesity, snoring and other sleep disorders, co-morbid pain conditions, head and neck injuries, stressful life events, smoking, caffeine intake, and overuse of pain medications. High frequency (9-14 days/month) episodic migraine has also been shown to increase the risk for progression to CDH.

Obesity has been shown in multiple studies to increase the risk of progression to chronic daily headache. Scher et al demonstrated an odds ratio of 5.53 for the one-year incidence of chronic migraine in obese subjects. Patients should be encouraged to aggressively pursue weight loss measures, including dietary modification and exercise. Consultation with a dietician may be necessary to develop an understanding of their current dietary intake and strategies for change. As in episodic migraine, snoring and sleep disorders are a risk factor for CDH progression from episodic, and this risk is independent of factors such as obesity. (13) Patients should be evaluated for sleep disorders and sent for polysomnography if obstructive sleep apnea or other physiologic sleep disorder is considered. Physicians need to take the time to counsel patients regarding sleep hygiene as described above. Adequate treatment of underlying sleep disorders can improve or resolve many types of headaches including migraine. (14)

Likely the most important role of the physician in preventing the progression from episodic to chronic headaches is to prevent the overuse of pain medications and the subsequent development of medication overuse headache (MOH). MOH is defined as 15 days of headache per month in the setting of overuse of medication for 3 months, and should remit within 2 months of discontinuation. However, care must be taken that one overused medication is not simply substituted for another, such as a patient stopping acetaminophen but changing to an ibuprofen/caffeine combination. It is estimated that 30% of CDH sufferers have MOH.

Medications of overuse can include over-the-counter medications such as acetaminophen and caffeine containing medications and prescription medications, most importantly opioid and butalbital containing compounds. Over-the-counter medications can be especially problematic because they are available without a prescription, very inexpensive, and often initially effective. Bigal and Lipton reported that "individuals with chronic migraine were more likely to be high caffeine consumers while they had episodic headaches, as compared with individuals that did not develop chronic migraine." (15) Patients must be advised against the frequent use of these medications, likely limiting their use to no more than 2 days per week. The AMPP trial revealed butalbital and opioids to be independent risk factors for the progression to Chronic Migraine from episodic over a one-year period, whereas other abortives such as triptans and non-steroidal anti-inflammatories were not. (16)

The AMPP trial also revealed that high frequency episodic migraine (914 days per month) was a risk factor for progression to chronic migraine, even without MOH. It is especially important for physicians and patients to adequately track migraine frequency and to consider aggressive preventive strategies discussed earlier such as pharmacologic treatment and trigger avoidance.

The only FDA approved treatment for Chronic Migraine (as opposed to the prevention of migraine) is the recently approved injection of onabotulinum toxin type A in a fixed site, fixed dose approach. It's use is limited by significant costs, insurance restrictions, and few providers trained in the injection paradigm.

Lastly, physicians need to be aware of the availability of vast numbers of patient educational resources online. While not all sources are of the same quality, there are a number of very well done and accurate sites to which patients can be directed for information regarding headaches and communication with other people who suffer similarly. Some examples of these include the National Headache Foundation (, the American Headache Society Committee on Headache Education (, and


After reviewing this article, the physician should:

1. Recognize the significant burden of migraine and headache disorders, especially on women

2. Have knowledge of both the pharmacological and non-pharmacological approach to the prevention of episodic migraine

3. Recognize and help patients avoid risk factors for the progression from episodic to chronic daily headache.


34. A 35 year old woman presents to your office with complaints of increasing frequency of migraine headaches. She is now having migraine three times per week. She is treating with sumatriptan and gets relief of her pain within two hours, but due to quantity limits by her insurance, is having trouble being able to treat all of her headaches. Which of the following is an apparent risk factor for her to develop chronic migraine?

a. Age of 35 years

b. Use of sumatriptan

c. Frequency of headaches between 9-14 per month

d. Lack of preventive medication use

35 A 42 year old man reports that he is now suffering from headaches at least 4 times per week, and often more than this. His headaches cause his nausea and he is sensitive to light and noise. He is having trouble maintaining his employment due to missing work. He is currently treating his headaches with a combination over-the-counter medication containing acetaminophen and caffeine. On review of systems he reports poor sleep and daytime fatigue. On exam he is obese with a BMI of 35, but has a normal exam otherwise. Which of the following is the most appropriate next step?

a. Advise to continue with his medication since it seems to work

b. Advise patient on exercise and weight loss and prescribe preventive medication

c. Switch patient from current medication to butalbital

d. Advise patient that there is nothing that can be done until he gets in shape

36. A 26 year old female with migraines occurring 18 days per month presents to your office for advice. She is otherwise healthy. She has been prescribed by another physician amitriptyline for prevention of her headaches without relief, and is using a butalbital/caffeine combination medication as needed for her headaches, but is seeing diminishing benefit. Her exam is normal. Which of the following is the most appropriate next step in the management of her chronic daily headache?

a. Advise her to increase the dose of her as needed medication to improve the benefit

b. Add another preventive medication

c. Advise her to alternate the use of her current as needed medication with over-the-counter medications

d. Advise her to eliminate the use of her as needed medication and provide alternative treatment with strict frequency limitations


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(5.) Nestoriuc Y, Martin A. Efficacy of biofeedback for migraine: a meta-analysis. Pain 2007 128 (1-2): 111-27.

(6.) Campbell JK, Penzien DB, Wall EM. Evidence-based guidelines for migraine headache: behavioral and physical treatments. US Headache Consortium 2000.

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(9.) Mannix LK. "Preventive Treatment of Migraine." Migraine in Women. Eds. Loder E, Marcus DA. London. BC Decker, 2004. 68-73.

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(11.) Lipton RB, Gobel H, Einhaupl, Wilks K, Mauskop A. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology 2004;63:2240-4

(12.) Bigal ME, Serrano D, Buse D, Scher A, Stewart W, Lipton R. Acute Migraine Medications and Evolution From Episodic to Chronic Migraine: A Longitudinal Population-Based Study. Headache 2008;48:1157-1168.

(13.) Scher AI, Midgette LA, Lipton RB. Risk Factors for Headache Chronification. Headache 2008;48:16-25.

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(15.) Bigal, ME, Lipton, RB. What predicts the change from episodic to chronic migraine? Current Opinion in Neurology 2009, 22:269-276.

(16.) Bigal ME, Serrano D, Buse D, Scher A, Stewart W, Lipton R. Acute Migraine Medications and Evolution From Episodic to Chronic Migraine: A Longitudinal Population-Based Study. Headache 2008;48:1157-1168.

Rajan Chopra, MD

Neurology Resident, WVU School of Medicine

Teri Robert, PhD

Executive Committee Member, Alliance for Headache Disorders Advocacy

David B. Watson, MD

Director, WVU Headache Center, WVU School of Medicine, Morgantown
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Title Annotation:Scientific Article: Special Issue
Author:Chopra, Rajan; Robert, Teri; Watson, David B.
Publication:West Virginia Medical Journal
Article Type:Report
Geographic Code:1USA
Date:May 1, 2012
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