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Chronic Migraine Headaches

An overview of current issues

Chronic daily headache is a disorder characterized by headache occurrence on at least 15 days per month for a minimum of 3 months. The most common subgroup of chronic daily headache is the migraine form.1 Increased frequency of migraine headaches has been linked to the overuse of pain medications or abortive medications.1,2 The effects of migraine can be disabling and thus influence productivity in the workplace. The total cost of lost work time due to headaches exceeds $19 billion.3

It is crucial for healthcare providers to recognize the disability that chronic migraines can cause. Many treatment and prevention options are available. In the case of chronic migraine headaches, prevention may be most important because overuse of abortive medications can exacerbate the problem. It is up to healthcare providers to determine which method of treatment and prevention is most appropriate for each patient.

Prevalence and Epidemiology

The prevalence of migraines in the United States is approximately 18.2% among women and 6.5% among men.3 Only about 66% of people who experience migraines seek healthcare for them. Of the people who consult a healthcare provider, 65.7% of women and 57.9% of men are properly diagnosed.3

Migraines occur most often between the ages of 25 and 55.3,4 One study determined that 3% of people with migraines developed a form of chronic daily headache within 1 year of the onset of migraines.5 An estimated 2% of the U.S. population experience chronic migraines.2,5 Although numerous medication options are available for prophylactic treatment of migraines, only 33.3% of people use them.2

When compared to other types of headaches, chronic migraine has the most impact on quality of life, lost school or work days, and the frequency of office and emergency department visits.3,5 Risk factors associated with the progression of migraine to a chronic frequency are female gender, white race, depression, anxiety, unemployment, unmarried status, low socioeconomic status, frequent migraine medication use, sleep-disordered breathing and high caffeine use.5,6            

Cause & Pathophysiology

The exact cause of migraine headache has not been proven. Migraine headaches apparently develop after the dilation of trigeminal nerve-innervating blood vessels.7 This is caused by the release of neuropeptides from parasympathetic nerve fibers surrounding the vessels. Therefore, neurovascular dysfunction is likely to be the pathogenesis of migraines. This leads to an inflammatory response and the pain that is experienced during a migraine.

The theory that neurovascular dysfunction causes migraine is based on the fact that the extracranial and intracranial vessels are innervated by the trigeminal nerve, which serves in both autonomic function and pain sensation.7,8 Several neurotransmitters have been linked to this phenomenon due to their roles in the treatment of acute migraines. The most notable are the serotonergic and calcitonin gene-related peptide.9

Serotonin actions may also play a role in migraine. Serotonin levels are increased during migraine headaches, but whether the migraine is directly caused by an increase in serotonin or the serotonin is released because of the headache is unknown. Women have a higher prevalence of migraine headaches then men.8 The serotonin theory is supported because brain scans show that men synthesize 5-HT faster than women.8

Medication overuse is the most common contributing factor to chronic migraines.6 The diagnostic criterion for overuse is the ingestion of headache medication for 10 or more days per month.10 Commonly overused headache medications are nonsteroidal anti-inflammatories (NSAIDs), triptans, ergots and opiates.5,10 Triptan overuse has led to a quicker onset of chronic migraines than use of ergots or NSAIDs.3 The overuse of these medications can double the risk of developing chronic migraines within 1 year of the onset of migraines.5

Studies show that 60% to 80% of people who experience migraine headaches have family members who also are affected.7 The neuronal mechanism or the genetic predisposition is not fully understood. Several studies have examined alterations of the 5-HT genes, but no clear correlation with migraines has been identified.8 Genetic studies have found that alterations in the gene for D2 and D4 receptors may cause hypersensitivity of dopamine at these receptors.9

Patient Presentation

Chronic migraine may be diagnosed in patients who experience migraine without aura at least 15 days per month for longer than 3 months.1,5,10,11 The classic sign of migraine headache is lateralized throbbing pain that occurs periodically. Onset usually occurs during the early adolescent years or early adulthood.11 Migraine headache pain may also be described as dull and generalized all over the head. Associated symptoms of nausea, vomiting, sensitivity to light, blurred vision and sensitivity to noise may be present.7,11 The pain and adverse effects usually build up gradually and can last for several hours at a time, depending on when treatment is initiated. Migraine headaches may be worsened by emotional stress and fatigue.7,11

Not all migraines present in the classic fashion. Thorough medical and social-psychological histories and a review of systems are vital when assessing a patient who has headaches. The Migraine Disability Assessment (MIDAS) test is a patient questionnaire that can help the provider determine the level of disability and pain experienced ( This information will assist in the selection of treatment.

Acute Treatment

Many people who experience chronic migraines report that certain environmental factors trigger their attacks.12 Avoidance of precipitating factors and the use of prophylactic medications are considered primary strategies. Guidelines from the American Academy of Family Physicians and the American College of Physicians-American Society of Internal Medicines state that NSAIDs are recommended as first-line treatment for acute migraine attacks.13 But overuse of these analgesics can cause overuse rebound migraines.6,11 In the emergency department, opiate narcotics are often as abortive agents, but a more specific therapy for migraines should be utilized.14 Narcotics should be avoided for the relief of acute migraines and as prophylactic therapy.7

One of the most popular classes of drugs for the treatment of severe migraines is the triptans. Triptans are selective 5-HT receptor agonists. Triptans have fewer adverse effects than other drugs used for migraine treatment.7 Sumatriptan can be administered subcutaneously or orally. The subcutaneous injections tend to provide quicker relief, but many people prefer oral administration.7 Triptans are contraindicated in people with heart disease, basilar or hemiplegic migraines, and in patients with uncontrolled hypertension.13 Another drug used for acute migraines is dihydroergotamine (DHE 45), which is also a 5-HT receptor agonist. This seems to be a more effective drug, but it can cause vomiting in a large percentage of patients.

The literature recommends that the use of medications for acute migraines be limited to two times per week. The selection of treatment should be individualized to each patient. Factors to consider are severity and frequency of the migraines, other related symptoms, level of disability, and medication cost.13

Preventive Medications                                           

The American Migraine Prevalence and Prevention study found that only 12.4% of people who met the guidelines to receive prophylactic medications were taking them.14 The implementation of preventive therapy for migraines has several goals: reduction in the severity and frequency of migraine attacks, reduction in the amount of acute migraine medication used, and improvement in overall productivity and quality of life.6 Sixty-six percent to 75% of people who have chronic migraines report overuse of pain medications and specific migraine medications.6

Since one of the main contributors to the development of chronic migraines is medication overuse, reducing the amount of medication taken for migraines is an initial step in attempting to prevent recurrence. The use of any opioid or butalbital should particularly be avoided due to their tendency to turn episodic migraines into a chronic form. The American Migraine Prevalence and Prevention Study suggests that this transformation tends to occur with only 5 days of butalbital use per month, 8 days of opioid use per month, 10 days of triptan or combination analgesic use per month, and 10 to 15 days of nonsteroidal anti-inflammatory use per month.14,15

Several medications have been studied in randomized, double-blind, placebo-controlled trials: amitriptyline (Elavil), topiramate (Topamax), gabapentin (Neurontin, Gralise), tizanidine (Zanaflex), fluoxetine (Prozac, Sarafem), and onabotulinum toxin type A (Botox).5 Amitriptyline and fluoxetine are antidepressants shown to be effective in migraine prevention via their effects as a serotonin reuptake inhibitor. Some anticonvulsants, such as gabapentin (Neurontin, Gralise), have shown promise in several trials, but further studies are needed to determine their true effect in migraine prophylaxis.16

Topiramate is one of the few medications that have been studied in a randomized, double-blind, placebo-controlled trial. It has an FDA indication for the treatment of migraines in adults. One of these trials looked at the safety and efficacy of using 100 mg/day of topiramate for the prevention of migraine headaches. The mean duration of therapy was approximately 90 days. The mean monthly number of migraines for the patients in the topiramate group was 17.1 days. The results after the treatment phase showed a reduction in the number of migraine days by 6.4 days per month. This was considered statistically significant when compared to the placebo group.

The most commonly reported adverse effect in the topiramate group was parethesia, which was reported in 28.8% of the group. Other reported adverse effects were fatigue, difficulty concentrating, dry mouth and nausea. The study concluded that a daily dose of 100 mg topiramate is significantly effective in reducing the number of monthly migraine days, with tolerable adverse effects if present.1 A smaller scale double-blind, placebo-controlled trial used 50 mg topiramate daily found that it may be just as effective in preventing migraine headaches as a higher dose and exhibit fewer adverse effects.6

Onabotulinumtoxin A is one of the newest and more recently studied medications for the prophylactic treatment of migraines. The exact mechanism is not fully understood, but studies indicate that the use of this medication inhibits the release of several neurotransmitters that inhibit neurogenic inflammation. Blocking the release of these neurotransmitters will inhibit peripheral sensitization of pain nerve fibers. The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials confirmed that onabotulinumtoxin A is a safe and effective prophylactic treatment for chronic migraines. This double-blind, parallel-group, placebo-controlled trial used a minimum intramuscular dose of 155 units in 31 injection sites within seven head and neck muscles. The maximum dose used was 195 units. The results demonstrated a reduction in migraine days of 8.4 days from baseline.

One of the more significant results from the trial was the tolerability of onabotulinumtoxin A when compared to other prophylactic medication. The discontinuation rate from adverse effects was only 1.4% to 3.8%, whereas many other medications have discontinuation rates of 12.7%.2

Topiramate and onabotulinumtoxin A produced similar results in these studies. Therefore, it is up to the provider to determine which therapy may be most appropriate. Several trials of different medications may be necessary to determine which works best for each patient.


The prognosis for people who experience chronic migraines is generally good. In many patients, migraines diminish with age.7 Studies show that, over time, approximately 42% of people with migraines experience remission and 38% experience only infrequent migraines.17 Although migraines usually decrease in frequency with age, they can get worse after menopause in some women and with the use of oral contraceptives.7 High frequency of migraine headaches with onset at a young age has been associated with a poor prognosis for migraine remission in later years.17 Successful use of prophylactic medications has significantly improved quality of life and productivity in people who experience chronic migraine headaches.

Brandon Glow is a physician assistant at Phoebe Orthopaedic Specialty Group in Albany, Ga. Laura Lee is a physician assistant who is an assistant professor in the PA program at Georgia Regents University in Augusta, Ga. The authors have completed disclosure statements and report no relationships related to this article. 


1. Silberstein SD, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache. 2007;47(2):170-180.

2. Blumenfeld A, et al. Method of injection of onabotulinumtoxinA for chronic migraine: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program. Headache. 2010;50(9):1406-1418.

3. Hazard E, et al. The burden of migraine in the United States: current and emerging perspective on disease management and economic analysis. Value Health. 2009;12(1):55-64.

4. Burton WN, et al. The impact of migraine and the effect of migraine treatment on workplace productivity in the United States and suggestions for future research. Mayo Clin Proc. 2009;84(5):436-445.

5. Vargas BB, Dodick DW. The face of chronic migraine: epidemiology, demographics, and treatment strategies. Neurol Clin. 2009;27(2):467-479.

6. Diener HC, et al. Treatment of chronic migraine. Curr Pain Headache Rep. 2011;15(1):64-69.

7. Ropper AH, Samuels MA. Headache and other craniofacial pain. In: Adams and Victor's Principles of Neurology. 9th ed. New York: The McGraw-Hill Companies, Inc.; 2009.

8. Panconesi A. Serotonin and migraine: a reconsideration of the central theory. J Headache Pain. 2008;9(5):267-276.

9. Charbit AR, et al. Dopamine: what's new in migraine? Curr Opin Neurol. 2010;23(3):275-281.

10. Olesen J, et al. The International Classification of Headache Disorders. Headache. 2008;48(5):691-693.

11. McPhee SJ, Papadakis MA. Nervous system disorders. In: Current Medical Diagnosis and Treatment 2012. 49th ed. New York: The McGraw-Hill Companies, Inc.; 2012: 872-875.

12. Kelman L. The triggers or precipitants of the acute migraine attack. Cephalalgia. 2007;27(5):394-402.

13. Snow V, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002;137(10):840-849.

14. Lipton RB, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-349.

15. Mulleners WM, Chronicle EP. Anticonvulsants in migraine prophylaxis: a Cochrane review. Cephalalgia. 2008;28(6):585-597.

16. Tepper SJ. Medication-overuse headache. Continuum. 2012;18(4):807-822.

17. Lyngberg AC, et al. Prognosis of migraine and tension-type headache: a population-based follow-up study. Neurology. 2005;65(4):580-585.





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