CHAPTER 10 Migraine Headaches
Migraine is a common, painful headache disorder that affects at least 10% of the general population. Migraine is more common in women than in men. The American Migraine Study II reported that 20.9 million women and 6.9 million men suffer from severe headaches.1 Prevalence varies with age: Migraines typically begin in childhood or adolescence and are most prevalent in young and middle-aged adults; the incidence of migraine generally declines after the fifth decade of life.2 In women, menstrual migraines begin at menarche, abate during pregnancy, and continue through menopause.3 Roughly half of all individuals who experience migraines consult a physician, and migraines are correctly diagnosed in about 50% of these patients. The remaining patients are often prescribed ineffective therapies, with many relying on over-the-counter medications.4 Chronic daily headache (CDH), which can be a consequence of poor migraine management, remains a significant cause of morbidity.5
CLASSIFICATION OF MIGRAINE HEADACHE
Migraine headaches are classified on the basis of criteria established by the International Headache Society (IHS). The IHS diagnostic criteria for migraine without and with aura are outlined in Box 10-1.
Box 10-1 Migraine headaches
Patients who have migraine with aura may experience visual auras (the most common symptom), parasthesias, paresis, and dysphasia. Auras are localized to the brainstem or cerebral cortex and may last as long as 60 minutes. An aura is typically followed by pain. In rare cases, an aura may be experienced without a subsequent headache, or it may be experienced concurrently with migraine pain.
PATHOGENESIS OF MIGRAINE
The vascular theory suggests that vasoconstriction is followed by vasodilation, aura, and finally, throbbing headache. Blood vessels in the cerebellum and meninges expand and contract at various rates, depending on blood-flow changes.6 Small blood vessels are dramatically stretched during these spasms, resulting in throbbing pain. A limitation of this theory, however, is that these changes in blood flow are neither correlated with headache intensity nor exclusive to migraine.
Although it is well known that muscle tension and contraction occur in tension-type headaches, electromyographic studies demonstrate greater muscle contraction in the patient with migraine; hence the muscular theory.7
The biochemical theory, also known as the cervicotrigeminovascular hypothesis, holds that migraine headaches are triggered by a decrease in the level of serotonin in the brain. Serotonin receptors on the trigeminal nerve inhibit the release of substance P. When the serotonin level decreases, the release of substance P is enhanced, thereby triggering vasodilation, local inflammation, and pain. It is thought that the trigeminal neurons spontaneously fire with the depolarization of the ophthalmic branch of this nerve. Substance P, a neurotransmitter, is then released, causing vasodilation and increased permeability. This leads to local inflammation and edema, which results in the unilateral frontal pain of a migraine. This models holds that neurogenic inflammation and vasoconstriction are the two major factors in the development of a migraine.
Menstrual Migraine
The precise definition of menstrual migraine remains a matter of controversy, and debate over what exactly constitutes the diagnosis continues.8 The IHS does not distinguish menstrual migraine as a separate entity from migraine without aura.9 However, most physicians and researchers agree that menstrual migraine is a migraine headache that occurs regularly each month but only between the second day before the menses and the end of menstruation. Menstrual migraine is believed to occur in approximately 14% of women. Menstrual migraine is thought to result from declining estrogen levels and interactions between estrogen and other biochemicals.10 Estrogen and progesterone have potent effects on central serotonergic and opioid neurons, modulating both neuronal activity and receptor density. One hypothesis holds that the decrease in estrogen during the late luteal phase makes the blood vessels more susceptible to compounds associated with migraines such as serotonin, substance P, norepinephrine, dopamine, endorphins, prolactin, and progesterone.11
From 1971 through 1994, 32 articles on menstrual migraine were published; however, the definition of menstrual migraine varied among these studies with respect to the timing and type of attacks.10 Researchers have investigated the effectiveness of extended-duration oral contraceptives to prevent fluctuations in estrogen. Although research clearly shows that only a few women experience relief with this regimen, women who experience menstrual migraines and are taking oral contraceptives may achieve a reduction in the number of attacks by changing to a low-dose monophasic oral contraceptive with an extended-duration regimen. Other treatments that have been studied include transdermal estrogen patches, which failed to show benefit12,13; two small open studies of tamoxifen, which showed benefit14,15; an open nonrandomized study with danazol, which showed benefit in women older than 40 years16; and leuprolide (with add-back hormone therapy) in an open study of 5 women, which indicated beneficial effects.17 Frovatriptan, 5 mg twice daily on the first dosing day, followed by 2.5 mg twice daily for 5 more days, has been shown to prevent menstrual migraine in 50% of women, compared with 26% of women given placebo when the treatment was started 2 days before the anticipated start of menstrual migraines.18 Naratriptan, 1 mg twice daily, taken 3 days before the anticipated start of the menstrual migraine and continued for 6 days, has also been found superior to placebo.19
TREATMENT
Once the diagnosis of migraine has been made, a thorough history of the illness must be gathered, including past treatments the patient has tried, frequency of headache, impact on quality of life, and the identification/elimination of any known triggers. A comprehensive headache treatment plan should include treatments for acute migraine attacks and long-term preventive therapy to reduce attack frequency, severity, and duration.
Studies demonstrate that acetaminophen, aspirin, ibuprofen, and an aspirin-acetaminophen-caffeine combination are more effective than placebo in reducing moderate or severe migraine pain to mild or no pain 2 hours after administration in patients who experience vomiting or severe disability with their migraines.20
Triptans are relatively safe and effective medications for the treatment of acute migraine. The differences among them are generally minor. Considerations in selecting a triptan include individual patient response/tolerance, characteristics of the patient’s attacks, relief of associated symptoms, consistency of response, headache recurrence, delivery systems, and patient preference.21
In both well-controlled single-episode studies and long-term multiple-episode studies, sumatriptan nasal spray has been effective and well tolerated in the short-term treatment of migraine in children and adolescents. Except for its unpleasant taste, sumatriptan nasal spray has a tolerability profile similar to that of placebo in young patients.22
Lifestyle Modification
Many people who experience migraines can identify triggers for the headaches. One hundred patients who fulfilled the diagnostic criteria for migraine without aura were evaluated through the use of a personal interview. Stress was the most frequently cited trigger, causing migraine in 76% of patients. Stress was followed, in descending order of frequency, by sensory stimuli (75%), sleep deprivation (49%), hunger (48%), environmental factors (47%), food (46%), menses (39%), fatigue (35%), alcohol (28%), sleep excess (27%), caffeine (22%), physical exertion (20%), head trauma (20%), travel (4%), sexual activity (3%), medication (2%), neck movement (2%), smoking (1%), and the use of a low-profile pillow (1%).23 A headache diary may help identify triggers, allowing practitioners and patients to develop a strategy for reducing the frequency of acute attacks.
Many factors can affect serotonin levels, including food allergies or sensitivities, certain drugs, fluctuating hormone levels, anxiety, and certain dietary deficiencies. As the serotonin level increases, the incidence of headaches usually decreases. The diminishing number of postsynaptic serotonin receptors that accompanies the normal aging process partly explains the reduction of migraine frequency that occurs with age.24
The list of foods, beverages, and additives that have been reported to trigger migraines includes cheese, chocolate, citrus fruits, hot dogs, monosodium glutamate, aspartame, fatty foods, ice cream, and alcoholic drinks (especially red wine and beer), as well as caffeine withdrawal. Tyramine, phenylethylamine, histamine, nitrites, and sulfites affect phases of the migraine process by influencing the release of serotonin and norepinephrine, causing vasoconstriction or vasodilation, or by directly stimulating the trigeminal ganglia, the brainstem, and cortical neuronal pathways.25 Patients should be informed of the most common food triggers and asked to keep a diary of acute attacks and their relation to any identifiable trigger.
Because stress has been cited as the most common precipitating factor, practitioners must help patients explore ways of managing or coping with stressful situations. A considerable body of evidence indicates that several mind/body therapies are effective in the treatment of headaches in adults26 and that psychological treatments—mainly relaxation and cognitive behavioral therapy—are effective in reducing the severity and frequency of chronic headache among children and adolescents.27 Although cognitive behavioral therapy has a great deal to offer individuals who experience recurrent headaches, issues surrounding cost and access are considerable in some populations. Many communities now offer classes in yoga, tai chi, relaxation, and fitness, and books written for the consumer provide tips for managing stress. Practitioners would be wise to familiarize themselves with community resources and steer patients toward such self-care initiatives when possible.
Dietary Supplements
Magnesium.
Research has been focused on the role of magnesium in the pathogenesis of migraine. A low magnesium level may cause brain hyperexcitability by opening calcium channels, leading to increased intracellular calcium levels, glutamate release, and extracellular potassium levels, which may in turn trigger the cortical spreading depression seen with migraine.28 A randomized, double-blind, placebo-controlled study was conducted to assess the efficacy of magnesium sulfate in patients with migraine with and without aura. Sixty patients in each group were randomly assigned to receive 1 g of intravenous magnesium sulfate or 0.9% physiologic saline solution. Seven parameters of analgesic evaluation and an analog scale for the assessment of nausea, photophobia, and phonophobia were used. No statistically significant difference in pain relief or nausea was seen in the migraine-without-aura group between patients who received magnesium sulfate and those who were given placebo; however, the intensity of photophobia and phonophobia was significantly lower. The migraine-with-aura group patients given magnesium sulfate had a statistically significant improvement in pain and all associated symptoms compared with that of controls.29 The findings of this study are consistent with those of a smaller trial involving 30 patients with acute migraine in which 1 g of intravenous magnesium was an effective treatment for the relief of pain and associated symptoms.30
The evidence for magnesium supplementation as a prophylactic agent is contradictory. A 12-week double-blind, placebo-controlled study of 81 patients, ranging in age from 18 to 65 years, with migraine (mean attack frequency 3.6 headaches per month) showed that 600 mg/day oral magnesium dicitrate (24 mmol/day) was superior to placebo in reducing the frequency of migraine attacks. During weeks 9 through 12, the attack frequency was reduced by 42% in the magnesium group and by 16% in the placebo group compared with baseline (P < 0.05). The number of days with migraine and drug consumption for symptomatic treatment per patient also decreased significantly in the magnesium group. Diarrhea (19%) and gastric irritation (5%) were reported in the active treatment group.31
This study is in contrast to a randomized, placebo-controlled study of 69 patients with two to six migraines per month without aura and a history of migraine of at least 2 years that studied magnesium as a prophylactic agent. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium aspartate (10 mmol twice daily) or placebo. The primary efficacy end point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared with baseline. Of the participants in the study, 35 had received magnesium and 34 had received placebo. The number of responders was 10 in each group. Magnesium demonstrated no advantage over placebo with regard to the number of migraine attacks or migraine days. With respect to tolerability and safety, 46% of patients in the magnesium group reported primarily mild adverse events (e.g., soft stool, diarrhea), in contrast to 24% of the placebo group. The study was discontinued before its completion because researchers were not able to identify any benefit of magnesium.32 It is unclear whether benefit would have occurred had the trial been continued for the full 12 weeks; the other preventive study found a strongly statistically significant difference between magnesium and placebo during weeks 9 through 12. The two studies also differed with regard to dose (the first study used more than double the dose) and magnesium preparation.
Until larger research trials are conducted to more adequately determine efficacy, optimal dose, and dosage form, some practitioners feel that given the relative safety and low cost of magnesium, a trial of a magnesium salt at doses of 200 mg twice daily or 400 mg four times daily makes good sense.33 Some preliminary data suggest that a low magnesium level is related to the development of menstrual migraine,34 and a 3 month-trial may be warranted in this group as well.
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