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Nonpharmacologic Management of Migraines
By Susan T. Marcolina, MD, FACP, Dr. Marcolina is a board-certified internist and geriatrician in Issaquah, WA; she reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
Part 1 of a Series on Migraines
Defined as a recurrent, disabling primary headache disorder, migraine is a chronic illness that requires a two-pronged management strategy: 1) treatment of the acute attack, and 2) mitigation of recurrences by balancing risk factors with physiologic resources for decreasing severity, duration, and frequency of the attacks. Although effective drug therapies exist for the treatment of migraines, patients may have contraindications to their use, such as poor tolerance, pregnancy, or side effects. If medication is overused, it can actually exacerbate headaches.1,2
Primary care physicians can guide patients toward nonpharmacologic treatment strategies that can be used alone or in conjunction with pharmacotherapy. A personal headache diary provides clues to the patients' headache history, which allow patients and their doctors to understand environmental, dietary, and lifestyle precipitants and seek appropriate interventions.3 Table 1 summarizes the International Headache Society's (IHS) diagnostic criteria for migraine.4 Application of these classification criteria for headache improves the accuracy of the headache diagnosis and reserves neuroimaging procedures for patients presenting with headache plus one or more of the "nine notable" features outlined in Table 2. These worrisome features are indicative of secondary headache disorders and can be seen in patients with and without previous migraine histories.
Public Health Implications
Migraine headaches are a common condition with a prevalence rate of 12-14% in the United States. Women experience them 3.3 times more than men. Lipton reported that 90% of migraineurs report functional impairment with their headaches, 53% of them exhibit impairment severe enough to require bed rest, and 51% report a 50% reduction in school or work productivity due to headache. The impact on household, family, and social activities is even greater.5
Pathophysiology of Migraines
The essential biologic element of the migraine condition is neuronal hyperexcitability, a condition that is often inherited but may also arise spontaneously or from central nervous system trauma. Common triggers for migraine attacks (see Table 3) destabilize the sensitive nervous system and result in headaches. Common migraine comorbidities such as generalized anxiety and panic disorder, depression and bipolar disease, insomnia, irritable bowel syndrome, epilepsy, and stroke confirm the presence of nervous system irritability.6
The pain of migraine headaches arises from trigeminovascular system activation, primarily mediated through serotoninergic (5HT) mechanisms. Disrupted activity at the vascular 5HT1b and neuronal 5HT1d receptors is postulated to result in vasodilation, nerve terminal activation, neurochemical release, and pain. A form of sterile neurogenic inflammation and blood-brain barrier breakdown occurs. Once intracranial branches of the first order trigeminal nerve (V1 or ophthalmic division) are stimulated, the nervous system is activated by second order trigeminal neurons in the brainstem and third order neurons in the thalamus and higher cortical centers. This activation sequence results in central neuronal sensitization along pain pathways of the upper cervical spine and activation of other brainstem nuclei. These processes account for migraine associated referred neck pain (reported in 75% of migraine patients), as well as autonomic symptoms of lacrimation, rhinorrhea, and nasal congestion (reported by 50% of migraineurs).7 Although these autonomic features are more typically seen in cluster type headaches, the key differentiating feature by IHS criteria is headache duration. While migraines typically last more than four hours, cluster headaches almost universally last less than four hours and occur more commonly in males.4
Diet. Dietary evaluation in the management of migraine is complicated since multiple triggers and variables can modify the pain threshold for an individual. For certain patients, primarily children and adolescents, food and food additives can be a significant precipitant of headaches. Such triggers are outlined in Table 3.8 Egger et al, in an old double-blind controlled trial of 88 children with severe, frequent migraines, showed that 93% fully recovered with institution of oligoantigenic diets.9
Caffeine. Caffeine withdrawal headaches have been reported after cessation of caffeine dosages as low as 100 mg/d (the equivalent of one cup of coffee or two cups of tea).10 These headaches begin within 24-48 hours after discontinuing caffeine and last for 1-6 days.11
Low-fat Diet. Bic et al conducted a prospective cohort trial of 54 migraine patients and found that lowering dietary fat intake from 66 g/d to 28 g/d resulted in a significant decrease in headache frequency, intensity, duration, and medication use (P < 0.001 for all measures).12
Exercise. Regular exercise is known to increase plasma beta endorphin levels. Koseoglu et al studied 36 patients with migraine who engaged in regular aerobic exercise three times weekly for 30 minutes over six weeks. Their pre-exercise beta endorphin levels were inversely proportional to the degree of improvement in their post-exercise headache parameters (P < 0.0001). Additionally, persons who exercise regularly increase their cardiovascular and cerebrovascular health, and experience improved psychological states with decreases in depression, anxiety, and stress.13,14
Sleep Patterns. Sleep patterns in migraine patients can be causal or contributory to their headaches. Overnight headaches or headaches upon awakening reflect a sleep disturbance in 55% of patients. It is important to rule out sleep apnea with a sleep study because treatment results in improvement of both headaches and general medical health.15 The Somogyi effect (marked fasting hyperglycemia following antecedent, usually asymptomatic nocturnal hypoglycemia) may also account for chronic morning headaches in patients with diabetes.16
Botanical Preventive Therapy
Feverfew (Tanacetum parthenium L.). The pharmacologic role of feverfew in migraine physiology is not completely understood, although it is known that feverfew extract causes serotonin release from platelets. Additionally, feverfew extracts and parthenolide, the principal ingredient in feverfew, inhibit prostaglandin synthesis.17
Pittler and Ernst, in an updated Cochrane Review, evaluated five randomized controlled trials involving 343 patients treated with feverfew extract for migraine headache prophylaxis. Results from these trials did not establish feverfew to be significantly more efficacious than placebo. They also noted difficulties with trial designs and contradictory results when ethanolic extracts of feverfew were used in trials vs. herbal powders in capsule form.18
Implementation of a supercritical CO2 extraction method produced a stable, standardized parthenolide extract called MIG-99. Using this extract, Pfaffenrath et al conducted a double-blind, placebo-controlled, randomized dose-response comparison of four parallel groups: three dosages of MIG-99 extract vs. placebo. The active treatment patients received either 2.08 mg MIG-99 (approximately 17 mg parthenolide), 6.25 mg MIG-99 (0.5 mg parthenolide), 18.75 mg MIG-99 (1.5 mg parthenolide), or placebo. Each dose was taken three times daily. Patients kept a headache diary during a four-week baseline period followed by the 12-week active treatment phase with MIG-99 or placebo. Overall, the researchers found no significant improvement in migraine headaches compared to placebo. However, in a small subgroup of patients with at least four headache attacks during the 28-day baseline period, MIG-99 extract at 6.25 mg three times per day significantly reduced migraine frequency after two months.19
Deiner et al, as a follow-up to this 2002 study, performed a second multicenter phase III prospective randomized controlled trial in which 170 patients were randomized to either the active arm and received MIG-99, 6.25 mg three times daily, or placebo. They reported that 30% of the feverfew group and 17% of the placebo group experienced a 50% or greater reduction in headaches/month (P = 0.047).20
Vitamins and Minerals
Riboflavin (Vitamin B2). Shoenen et al, in a randomized, controlled trial of 55 patients treated with either riboflavin 400 mg/d or placebo, demonstrated that after three months of supplementation with riboflavin, there was a statistically significant reduction of headache attack frequency (P = 0.005) and headache days (P = 0.012).21
Magnesium. Peikert et al, in a three-month randomized, double-blind, placebo-controlled trial of 81 adults with migraine, showed that 600 mg of magnesium (trimagnesium dicitrate) reduced the headache frequency by 41.6% compared to a reduction of 15.8% for the placebo group.22 The drawback was an 18.6% incidence of diarrhea among those in the magnesium treatment arm.
Facchinetti et al, in a small study of 20 women with menstrual related migraine headaches, found that if patients were given 360 mg/d magnesium during the luteal phase of the menstrual cycle, the number of days with migraine were significantly reduced (P < 0.03). They also noted an inverse correlation between the Pain Total Index questionnaire and magnesium levels in the polymorphonuclear leukocytes (PMNs), which supports the theory that a lower migraine threshold could be related to magnesium deficiency.23
Coenzyme Q10. Coenzyme Q10 (CoQ10) may produce beneficial effects for migraine prevention in two unique ways: it may affect mitochondrial function and energy production at the molecular level and it functions as an antioxidant. It is the only lipid-soluble antioxidant synthesized in living cells. Up to 80% of human CoQ10 is intrinsically synthesized and is widely distributed in all cellular membranes, which has resulted in its alternative name, ubiquinone. Dietary CoQ10 intake is primarily from meat and poultry, although Weber et al have observed that diet alone cannot replenish a deficient state.24
Tang demonstrated that migraineurs have altered expression of mitochondrial-related genes both during acute headaches and between attacks. Therefore, if the mitochondrial response is limited or inhibited due to deficiency of CoQ10 substrate, more severe or frequent migraine headaches may be expected.25 Hershey et al showed that supplementation of CoQ10-deficient pediatric and adolescent migraine patients and subsequent normalization of total CoQ10 levels significantly decreased headache frequency, and improved quality of life and Pediatric Migraine Disability Questionnaire (Ped MIDAS) scores.26
Recent large-scale standardized references levels have been established and allow for the determination of CoQ10 deficiency. Of note, since elevated cholesterol levels artificially increase levels of CoQ10, a correction is needed to detect deficiency states.
Hershey et al have recommended supplementation of migraine patients found to have total CoQ10 levels below 700 mg/mL or CoQ10:cholesterol ratios below 0.350 mg/mL. Depending upon clinical circumstances, headache patients who have such deficiencies should be treated and their clinical responses monitored.27,28
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19. Pfaffenrath V, et al. The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis—a double-blind, multicentre, randomized placebo-controlled dose-response study. Cephalalgia 2002;22:523-532.
20. Diener HC, et al. Efficacy and safety of 6.24 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention—a randomized, double-blind, multicenter, placebo-controlled study. Cephalalgia 2005;25:1031-1041.
21. Schoenen J, et al. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50:466-470.
22. Piekert A, et al. Prophylaxis of migraine with oral magnesium: Results from a prospective multicenter, placebo-controlled and double-blind randomized study. Cephalalgia 1996;16:257-263.
23. Facchinetti F, et al. Magnesium prophylaxis of menstrual migraine: Effects on intracellular magnesium. Headache 1991;31:298-301.
24. Weber C, et al. Coenzyme Q10 in the diet—daily intake and relative bioavailability. Mol Aspects Med 1997;18(Suppl):S251-S254.
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26. Hershey AD, et al. Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache 2007;47:73-80.
27. Hershey A, Pesce A. HPLC analysis of reduced and oxidized coenzyme Q(10) in human plasma. Clin Chem 2001;47:256-265
28. Schulz C, et al. Comparison of the relative bioavailability of different coenzyme Q10 formulations with a novel solubilizate (Solu Q10). Int J Food Sci Nutr 2006;57(7-8):546-555.