Headache

CHAPTER 12

Headache Remy R. Coeytaux, MD, PhD  •  John Douglas Mann, MD

Headache is one of the most common complaints that brings a patient to the attention of health care providers.1 Ninety percent of all headaches are either migraine, with or without aura; tension-type headache (TTH); or a mixture of the two. Sixteen percent of adult women and 6% of men suffer from migraine.2 The remaining 10% of headaches seen by caregivers are secondary to disorders of the tissues of the head and neck, including the cervical spine, sinuses, temporomandibular joints, and dental structures and soft tissue trauma and posttrauma, with primary tumors, infection, and metastatic cancers constituting a small fraction of the possible causes. “Red flag” symptoms of life-threatening disorders include early morning headaches that awaken the patient; visual dimming or double vision; headaches that are increasing in frequency or severity over weeks to months; headaches made significantly worse by postural changes; explosive onset of new, severe head pain; and headaches associated with mental status changes, focal motor or sensory deficits, syncope, seizures, fever, or stiff neck. Headaches in the setting of systemic illness, weight loss, human immunodeficiency virus (HIV), or known malignancy clearly require thorough investigation. Findings on examination that prompt further diagnostic workup include focal neurological signs, evidence of head or neck trauma, temporal artery tenderness, papilledema, nuchal rigidity, fever, and physical evidence of local or systemic infection or malignancy. Clinical guidelines are available for pharmacological prevention and treatment of migraine3-5 and tension-type headache.6 The emphasis in this chapter is on nonpharmacological, behavioral, nutritional, and complementary therapies that are effective in the treatment or prevention of migraine and tension-type headache.

MIGRAINE PATHOPHYSIOLOGY Characteristics typical of migraine include subacute onset of throbbing head pain (unilateral or bilateral) associated with nausea and vomiting, photophobia, and sonophobia. Headaches are heralded by visual or other nonpain premonitory symptoms (auras) in about 20% of those with migraine. The duration is usually more than 4 hours and may last up to 72 hours with fluctuating intensity.7 The precipitating factors can include menses, specific foods, stress or letdown following stress, changes in the weather, infection, fatigue, and bright sunlight. While the origin of migraine pain is not fully understood, recent evidence points to a role for potent vasodilators, such as substance P and calcitonin gene-related peptide (CGRP), released by peripheral nerve endings of 108

cranial nerve V on blood vessels in the scalp and meninges8 (Fig. 12.1). This leads to sterile inflammation and edema of blood vessels, with increased sensitivity to mechanical stimulation, resulting in pain. Glutamate, nitric oxide, and vanilloid receptors are also implicated in migraine. Translation of this information to therapy is very active. For instance, CGRP receptor antagonists are currently in phase III clinical trials.9,10 In the periphery, release of serotonin by platelets in the early stages seems to increase pain and prolong the headache. Centrally, the presence of a “headache generator” in the midbrain and pons is supported by findings from positron emission tomographic studies obtained during migraine attacks. Genetic influences are evident in a majority of patients with one or more family members experiencing migraine. Although the individual attacks of migraine are often stereotypic, variation is not uncommon and comorbid TTH is frequent.

Patients with migraine often suffer from tension-type headaches (TTH) and other forms of headache. A carefully recorded history of headache symptom characteristics helps establish criteria that lead to diagnoses and helps highlight distinctions that guide specific therapies.

The following sections describe complementary approaches that are potentially useful for integration with conventional therapies in the treatment of migraine (Table 12.1). Conventional approaches rely heavily on pharmaceutical interventions to prevent or abort headaches and are usually prescribed with analgesics and antiemetics. Although these measures are by themselves generally effective in the management of symptoms, they are often expensive; come with significant side effects; and do not address the underlying physical, psychological, and energetic issues that lead to headache. Patients with headache currently use a variety of alternative and complementary therapies,11 many of which will be reviewed in this chapter.

INTEGRATIVE THERAPY Lifestyle Effective management of migraine requires a careful assessment of lifestyle issues related to sleep, nutrition, exercise, stress management, and relationships. Regularizing meal times, developing an exercise routine, and correcting poor sleep can significantly reduce the frequency of migraine.12,13 Sleep hygiene guidelines are readily

12  Headache Dura Blood vessel

Primary sensory cortex

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Secondary sensory cortex Thalamus

Branch of ophthalmic division of trigeminal nerve

Amygdala Trigeminocervical complex Trigeminal nerve Bainstem

FIG. 12.1  □  Pathophysiology of headaches. (From Nicolson Stephen E. Massachusetts General Hospital comprehensive clinical psychiatry. 4th ed. Philadelphia, Elsevier Inc; 2016:78, 839-851)

Ophthalmic division of trigeminal nerve Trigeminal nerve Blood vessel Proposed pain pathway

TABLE 12.1 Summary of Migraine Therapies Types of Therapy

Specific Examples/Comments

Preventive Lifestyle

Sleep hygiene, exercise, stress management

Nutrition supplements—botanicals

Elimination of “food triggers,” consideration of food allergy, maintenance of good hydration. Magnesium, riboflavin, coenzyme Q10, omega-3 fatty acids, α-lipoic acid Feverfew, petasites, melatonin, and valerian root (sleep); ginger root (nausea)

Pharmaceuticals

Tricyclic antidepressants, β-blockers, calcium channel blockers, anticonvulsants, NSAIDs, botulinum toxin; reduction of the risk of analgesic rebound headache by addressing analgesic polypharmacy

Mind-Body Techniques Biofeedback

Motivation required to practice and use as a life skill

Relaxation

Progressive muscle relaxation, focused breathing exercises, guided imagery

Cognitive-behavior therapy

Modification of maladaptive thoughts and reactions to feelings and sensations

Neurolinguistic programming

Alteration of the subjective experience of pain and modification of expectations

Self-hypnosis

Use for both headache prevention and pain control

Mindfulness meditation

Improvements in mood, coping, blood pressure, muscle tone, pain control, and pain perception

Body work

Craniosacral therapy and chiropractic

Bioenergetics

Effectiveness in both preventing and treating migraine

Abortive and Acute Pharmaceuticals

NSAIDs, ergot alkaloids, isometheptene, intranasal lidocaine, triptans, valproate, magnesium, narcotics, antiemetics (ginger)

Chiropractic, massage

Use especially for headaches associated with neck discomfort

Acupuncture

Use for severe acute attacks

NSAIDs, nonsteroidal antiinflammatory drugs.

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available, easy to implement, and often lead to a decrease in both duration and frequency of migraine.14

Supplements

Nutrition

Levels of ionized tissue magnesium are often low in migraine, especially in individuals with menstrual migraine.24-26 There is limited evidence that suggests that oral supplementation with magnesium may be effective in the prevention of migraine.27 The mechanisms leading to improvement with magnesium supplementation may include reduction in cerebral cortical neuronal excitability or alteration in magnesium-dependent circadian regulatory mechanisms that are frequently disturbed in migraine.28-30 One study showed that oral magnesium dicitrate 600 mg given once a day significantly reduced the frequency of migraine compared to placebo.31 In another study, oral administration of 360 mg of pyrrolidine carboxylic acid magnesium daily for 2 months was associated with greater pain relief than placebo in women with menstrual migraine.32 Patients with menstrual migraine should continue magnesium for at least 3 months to determine the effectiveness because beneficial effects may be delayed for several cycles. Preventive benefit can be achieved with oral potassium magnesium aspartate (500–1000 mg/day at bedtime). Magnesium oxide is more readily available and cheaper than other forms, but it is poorly absorbed, especially when combined with calcium, zinc, or iron. Magnesium may cause diarrhea, particularly in those with irritable bowel syndrome, a common comorbid condition. For acute treatment of migraine, 2 g in 100 mL of saline given IV over 30 min appears to be effective and safe in an outpatient setting,33-35 but the U.S. Food and Drug Administration (FDA) issued a warning in 2013 about potential harm to the fetus associated with prolonged use of IV magnesium sulfate during pregnancy.36

Dietary choices clearly influence migraine, and exploration of diet is an important therapeutic avenue for improving migraine outcomes15; regularity in the diet may be the key to migraine control.16 Dietary triggers are found in 8%–20% of patients with migraine.17 Red wines, dark beers, aged cheese, some nuts, onions, chocolate, aspartame, and processed meats containing nitrates (such as hot dogs and pepperoni) are common offenders. Specific mechanisms may include direct effects of ingested substances on neuronal receptors governing headache or allergic responses to foods such as gluten and dairy products. A thorough history and testing for specific food allergies are key in the management of recurrent and chronic headache. Patients often know which foods they should avoid, but it is important to raise the possibility of dietary triggers with patients as these sometimes go unnoticed until they are brought up and discussed. Caffeine is a dietary factor that is particularly important. Caffeine withdrawal can temporarily exacerbate migraine or TTHs, whereas caffeine taken during a migraine can reduce pain in some patients, possibly due to its vasoconstrictive effects on the scalp and meningeal vessels. However, caffeine excess (more than five cups of coffee per day) can contribute to maintaining chronic daily headache, especially when combined with medication excess (see Chapters 31 and 86). Diets that contain large quantities of omega-6 fatty acids are generally proinflammatory and are likely to aggravate migraine and chronic TTH. In a study of 65 adults with chronic daily headache, of which 85% had chronic migraine, there was significant improvement in headache severity and frequency in those on a high omega-3, low omega-6 fatty acid diet compared to baseline and compared to those on a low omega-6 fatty acid diet alone.18 The dietary interventions lasted 12 weeks. Food was provided, and all subjects received regular dietary counseling throughout the intervention. Fatty acid supplements were not given. Clinical benefits were most pronounced in the last 4 weeks of the intervention. Most striking were the correlations between clinical improvement and levels of omega-3–derived antiinflammatory lipid mediators. Biochemical endpoints correlated closely with clinical improvement in pain and psychological distress19 (see Chapter 88). Obesity and metabolic syndrome have also been found to be associated with migraine and chronic headache, perhaps related to the proinflammatory state associated with these conditions.20-22 Inflammatory bowel disorders also have a higher incidence of migraine.23 Treatment implications for migraine in these conditions, while not fully defined, favor integration of dietary choices with other forms of treatment. Specific nutrients and supplements that have shown promise in headache management are reviewed in the following text.

Magnesium

Dosage For prevention: potassium magnesium aspartate 500–1000 mg at bedtime Precautions May cause diarrhea; consider magnesium gluconate as an alternate form

Riboflavin (Vitamin B2) Patients with migraine have been shown to have reduced phosphorylation potential in brain and muscles, suggesting a mitochondrial defect in electron transport.37 Riboflavin is a precursor for two coenzymes involved in electron transfer for redox reactions. One hypothesis for the mechanism of action of riboflavin is that it improves mitochondrial energy reserves without changing neuronal excitability.38 In several clinical studies of riboflavin as a supplement in migraineurs, there were significant preventive effects.39,40 It may have synergistic preventive effects when used concurrently with a beta-blocker.38 There are no head-to-head studies comparing riboflavin

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with other preventive measures. Results in children with migraine are mixed.41,42

Dosage The recommended dose of riboflavin is 200 mg twice daily with meals. Precautions Riboflavin is well tolerated and does not influence metabolism of other agents. Patients may notice that color of their urine turns to intense yellow with daily use. It is safe in pregnancy.

Coenzyme Q10 The rationale for studying coenzyme Q10 relates to lower phosphorylation potentials found in patients with a variety of chronic disorders including migraine.43 The findings of an open-label trial showing reduction in headache frequency at 3 months with daily dosing of 150 mg of coenzyme Q10 were confirmed in a double-blind, placebo-controlled, randomized trial in 42 patients with migraine.44,45 The oral coenzyme Q10, 100 mg three times a day, resulted in a reduction in attack frequency by 47.6% compared to 14.4% in the controls at 3 months. The number of days with headache was also significantly reduced. Like riboflavin, there was no change in headache intensity or duration once a headache occurred. Another clinical trial published in 2011 demonstrated early (but not sustained) benefits associated with coenzyme Q supplementation for the prevention of migraine in children and adolescents.46 There have been no major recent studies.

Dosage Coenzyme Q10, 150 to 300 mg/day; minimum 3-month trial based on research of Sandor and associates.24 Precautions Well tolerated with rare gastrointestinal side effects, is relatively expensive, and safe in pregnancy.

Fish Oil Rationale for the use of omega-3 fatty acids in migraine prevention includes their antiinflammatory properties, vascular relaxation effects, and inhibition of serotonin release from platelets. Only two studies in the last 15 years specifically address the role of omega-3 supplements in migraine. The American Academy of Neurology (AAN) Guidelines for Headache (2013) ranked the evidence as insufficient to make recommendations. One study of fish oil capsules for migraine prevention used a randomized crossover design in 27 adolescents with migraine; it compared daily omega-3 fatty acids vs an olive oil control, both given as capsules, with no change in the diet. Each arm was 2 months with a 2-week washout. Both olive oil and omega-3 were associated with a striking reduction in headache frequency compared to baseline and

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washout frequencies.47 There were no measures of compliance or biochemical endpoints and no follow-up. Another study of fish oil capsules in 96 adults with migraine showed no benefit.48 The dosing ranged between 2 and 6 g/day, and there was no recommendation to change the usual diet of subjects. Side effects included nausea and symptoms of gastric reflux. A recent diet-only study of adults with chronic migraine on omega-3-enriched diet for 12 weeks, without supplements, showed significant benefits in headache by week 9 of the intervention, which increased further during the last 3 weeks, compared to a reduced omega-6 diet.18 It is safe during pregnancy.

Dosage According to the available literature, it is best to increase omega-3 fatty acid levels through nutrition rather than taking it as a supplement.

Daily use of a compound containing 400 mg of riboflavin, 300 mg of magnesium, and 100 mg of feverfew has been shown to be effective in reducing the frequency of migraine in adults.49

Botanicals Feverfew (Tanacetum parthenium Leaf) Johnson et al. reported a significant increase in migraine severity and frequency when feverfew was stopped in a small group of migraineurs taking it for prevention.50 In one well-designed study, a 70% reduction in headache frequency and severity was shown in 270 patients with migraine.51 Variations in the standardization of the dried leaf constituents confound replication studies of this herb. A reproducibly manufactured extract of feverfew has shown preventive efficacy in a double-blind randomized controlled trial (RCT).52 There are no long-term studies documenting safety and no head-to-head trials with other preventive medications. The mechanism of action in migraine may be related to its inhibiting effects on platelet aggregation and inflammatory promoters, such as serotonin and prostaglandins, or possibly its effect in dampening vascular reactivity to amine regulators of blood flow. Dosage Oral administration of feverfew up to 125 mg/day of the dried leaf standardized to a minimum of 0.2% parthenolide. Beneficial effects may take weeks to develop. Precautions Aphthous ulcers and gastrointestinal irritation develop in 5%–15% of users. Abrupt cessation of feverfew occasionally results in agitation and increased headache. It is not recommended during pregnancy due to prolongation of bleeding times.

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Butterbur (Petasites hybridus Root) In a large, three-arm, dose-finding RCT of a standardized extract of the root of this perennial shrub, it was found that migraine attack frequency was reduced by almost 50%. Among those on the highest dose, 68% had a 50% or greater reduction in headache frequency.53 This effect continued for at least 4 months. One smaller study showed similar results,54 and another study in 108 children and adolescents with migraine was also positive.55 One study that compared butterbur root extract to both music therapy and placebo in the prevention of migraine in children had mixed findings, with butterbur demonstrating efficacy compared to placebo in the long-term, but not short-term, follow-up.56 A systematic review of the published literature on the effectiveness of P. hybridus revealed that higher dose extracts (150 mg) were associated with a lower frequency of migraine attacks after 3–4 months compared to a lower dose and placebo.57 The extract is commonly standardized to 15% of the marker molecule (petasins) and known carcinogens are removed. Drug–herb interactions have not been studied.

Dosage Butterbur, 50 mg three times a day for 1 month; then 50 mg twice a day Precautions Unknown effects in pregnancy; excessive belching as a side effect

Dosage Melatonin, 2–12 mg; start at 2 mg and titrate up every 4 days as needed for sleep. Lower doses are needed if taken each evening for several weeks. Higher doses (>15 mg) are needed to acutely induce sleep over several days (jet lag). Precautions Fatigue, drowsiness, dizziness, abdominal cramps, and irritability

Valerian (Valeriana officinalis Root) When taken at night for sleep, valerian rarely results in residual drowsiness on awakening. It is nonaddictive and useful as an anxiolytic when given during the daytime (up to 250 mg three times per day). It does not impair psychomotor or cognitive performance.63 The mechanism of action includes stimulation of the central nervous system gamma-aminobutyric acid (GABA) receptors along with enhanced release and inhibition of reuptake of GABA. In clinical trials, including the use for sleep and anxiety, it has been judged to be safe.63-66 Gastrointestinal irritation is the most common side effect (15%).

Dosage Valerian, 100–300 mg of the extract standardized to 0.8% valerenate at bedtime or 250 mg every 6 hours for anxiety Precautions Very unpleasant smell that may aggravate nausea during migraine. It may cause worsening of tension headache if taken regularly for more than 3 months. It should not be used during pregnancy.

Supplements for Sleep Sleep management is a major therapeutic strategy in helping patients gain control over their headaches. Melatonin and valerian root can be used on a temporary basis to improve sleep.

Magnesium aspartate, in contrast to magnesium oxide, is easily absorbed and rarely causes diarrhea when used for migraine prevention. Avoid giving either preparation at the same time as calcium, zinc, or iron. Dosage: 500–1000 mg each night.

Melatonin Melatonin is used in the management of migraine to improve sleep and circadian rhythms. Sleep maintenance, as opposed to sleep induction, is improved with melatonin. Melatonin is recommended every night for 4–6 weeks and then tapered off. During that period, a sleep hygiene program can be put into place to reduce the need for the supplement. There are few side effects. Leone and coworkers demonstrated that a daily intake of 10 mg of melatonin for 14 days significantly reduced cluster headache frequency.58 Others have shown beneficial effects of melatonin in migraine and other types of headache, including migraine prevention in children.59-61 However, a recently published, double-blind, placebo-controlled, crossover study comparing extended-release melatonin at a dose of 2 mg 1 hour before bedtime did not demonstrate improvement in migraine frequency compared to placebo.62

Pharmaceuticals There is no inherent difficulty in the integration of conventional and complementary approaches in the treatment of headache. Conventional pharmacological therapy includes use of preventive and abortive medications. The pharmaceutical approaches discussed here are the ones for which there is greatest evidence of efficacy and clinical usefulness.3-5 Preventive Pharmaceutical Therapies Application of preventive pharmacological therapies in practice is typically organized around classes of medications, including tricyclic antidepressants, selective serotonin reuptake inhibitors, beta-blockers, calcium channel blockers, anticonvulsants, and other

12  Headache

miscellaneous agents. The goals are reduction in headache frequency and severity, improved function, and increased responsiveness to abortive and analgesic agents. The decision to start preventive therapy is based on the following: (1) headache frequency of more than two per month or more than 3 days per month lost to headache, (2) willingness of the patient to take a medication or supplement daily for at least 3 months, and (3) ability to maintain a headache diary. Medications for prevention are administered according to the half-life and a schedule that minimizes side effects. Effectiveness is best measured by having the patient maintain a headache diary, noting headache frequency and intensity as well as significant life events, such as stressful circumstances, menses, vacations, and major changes. Patients may respond to any of several beta-blockers (e.g., propranolol, atenolol, metoprolol, or timolol), making the choice of an agent highly individualized. It is not possible to predict who will respond to a given agent in advance, although the history of a family member who achieved effective prevention with a given agent may guide initial choices. Comorbid depression, a history of active asthma, and thyroid disease limits the use of beta-blockers, whereas obesity limits the use of tricyclic antidepressants and valproate. Medications and supplements are prescribed one at a time and tapered up to a maximum dose or until satisfactory benefit is realized at lower doses. Most drugs are started at less than half the predicted maximum dose. Often, patients achieve satisfactory results at doses well below the maximum, particularly with the tricyclic antidepressants. On the other hand, verapamil usually has to be given at doses of at least 320 mg/day for benefit to occur. Magnesium, vitamin B2, coenzyme Q10, and daily aspirin mix well with conventional preventive agents. Once improvement is achieved, the medication combination is continued for a period of 3–6 months with periodic gradual reductions in one or more agents to determine the minimum effective dose. Effective preventive agents allow time for patients to work on lifestyle issues, including management of stress, sleep, nutrition, and exercise, as well as to develop life skills, such as relaxation, biofeedback, and self-hypnosis. Preventive agents are also chosen to facilitate the treatment of comorbid depression and sleep dysfunction. As patients improve, diaries that focus on pain are discontinued. Tricyclic Antidepressants. Amitriptyline, in doses of up to 150 mg at bedtime, starting as low as 10 mg, is effective for prevention. A few patients do well on very low doses such as 10 mg at night. Other useful medications in this group include nortriptyline, up to 100 mg at bedtime. Sleep is often improved, which reduces migraine frequency. Dry mouth, morning drowsiness, and constipation are significant side effects. Beta-Blockers. Medications in this class that have been shown to be effective for migraine include propranolol,

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nadolol, timolol, atenolol, and metoprolol. Long-acting formulations have not been formally studied. Side effects include fatigue, depression, insomnia, dizziness, and nausea. Rebound headaches may occur if beta-blockers are suddenly withdrawn. Dosing of propranolol for migraine prevention ranges between 80 and 240 mg/day in two or three divided doses. Calcium Channel Blockers. Calcium channel blockers shown to be effective include verapamil, nimodipine, flunarizine, and nifedipine. Delayed onset (weeks) of effectiveness is typical, and side effects such as abdominal pain, bloating, weight gain, constipation, and even headache are not uncommon. A typical dose of verapamil is 180 mg twice daily. Anticonvulsants. The major members of this group prescribed for migraine are sodium valproate, gabapentin (Neurontin), topiramate (Topamax), zonisamide (Zonegran), and levetiracetam (Keppra).67,68 A typical adult dose of sodium valproate for prevention is 1500 mg/day, with a starting dose of 250 mg twice daily. Side effects include weight gain, alopecia, tremor, and nausea. Sodium valproate is available in 125-, 250-, 500-mg, and sustained-release formulations. Topiramate is the most consistently effective of the four most commonly used drugs in this class, but cognitive side effects and nausea can be limiting. Levetiracetam and zonisamide have the fewest side effects. Nonsteroidal Antiinflammatory Drugs. Trends toward reduction in migraine frequency have been seen with daily use of aspirin, naproxen, ketoprofen, and tolfenamic acid. Gastric side effects are common, and patient compliance is poor. Dosages include naproxen 500 mg twice daily, aspirin 350–975 mg/day, and ketoprofen 150 mg/day. These drugs are not safe in pregnancy. Botulinum Toxin. Botulinum toxin has been found to prevent migraine when injected in small quantities at multiple sites into the muscles of the forehead, temples, posterior neck, and the trapezius muscle.69-73 The early Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) studies showing efficacy have been confirmed.74-76 The FDA has approved it for treatment of chronic migraine (>15 headache days per month). The positive response rate in those with chronic migraine is more than 60%. The frequency of chronic migraine is reduced significantly, whereas headache intensity remains largely unchanged. Effects last an average of 2–4 months. There is limited evidence on its efficacy in TTH. Side effects are few and can include transient weakness of injected muscles. Dosing is 100–200 units total per injection session. It is injected with a 27-gauge needle over 15–25 sites (∼2– 10 units per site). Abortive Pharmaceutical Therapies The following is a list of medications that, when taken early in the course of migraine, can abort further development of the headache.

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Nonsteroidal Antiinflammatory Drugs. Ibuprofen (800 mg) and naproxen sodium (200–400 mg) can block headache progression when given during the first few hours when the headache is building. Ibuprofen in liquid form (200–400 mg) is recommended when nausea occurs early in the headache. Individual variation in responsiveness to nonsteroidal antiinflammatory drugs (NSAIDs) is high; thus, it is worth trying several different agents from this class early in the headache. Ergot Alkaloids. Now largely supplanted by the triptans, ergot alkaloids can be useful in those who cannot tolerate other abortive methods. A typical dose is ergotamine tartrate, 1 mg orally, 2 mg sublingually, or dihydroergotamine (DHE-45) 2 mg subcutaneously (self-injection) every 4 hours for up to three doses. A nasal inhalational form is also available. Isometheptene. Isometheptene (Midrin) has a low sideeffect profile and modest cost. It is a weak vasoconstrictor of scalp vessels. The dosing is two or three capsules at the start of a headache, then one every 45 minutes for three more doses as needed within 24 hours. Intranasal Lidocaine. Intranasal lidocaine is effective for most forms of migraine and is particularly useful when given during the aura and when nausea and vomiting are prominent early in the headache.77 The mechanism may relate to the anesthetizing effects of lidocaine on sphenopalatine ganglia. Lidocaine (4% liquid) is applied with a dropper, 0.25–0.50 mL up each nostril, with the patient supine and the head hyperextended. Side effects include a mild transient burning sensation in the nasal passages and occasional transient numbness in the throat. The nasal spray form of lidocaine is generally ineffective. Repeat dosing can be done hourly for 4–6 hours. Intranasal ketorolac has also shown promise for the acute treatment of migraine.78 Triptans (5-Hydroxytryptamine Receptor 1B/1D Agonists). The triptans, on average, are the most effective agents available for aborting migraine.79-82 They act by blocking the release of inflammatory cytokines from the distal nerve endings of the trigeminal system onto the scalp and meningeal vessels and by their vasoconstrictive effects on scalp vessels. Multiple products are available by prescription, including tablet or melt forms, selfinjection kits, and nasal sprays. Efficacy of a single dose is 60%–80% for pain and nausea relief, with a 25%–30% recurrence rate necessitating a second dose. The choice of a triptan depends on patient response, side-effect profile, and preferred route of administration. Long-acting forms, including naratriptan (Amerge) and frovatriptan (Frova), can be effective when recurrence rates are noted with the more rapidly acting triptans. Oral melt formulations and nasal sprays are useful when nausea is prominent early in the headache. Usual dosing is at 2-hour intervals, if necessary, for a maximum of three doses in 24 hours. • Sumatriptan (Imitrex): 25-, 50-, and 100-mg tablets; 20-mg nasal spray; and 6- and 4-mg/0.5 mL injection kits

• N  aratriptan (Amerge): 1- or 2.5-mg tablets • Rizatriptan (Maxalt): 5- or 10-mg tablets or melt tablets • Zolmitriptan (Zomig): 2.5- or 5-mg tablets or melt tablets • Almotriptan (Axert): 12.5-mg tablets • Frovatriptan (Frova): 2.5-mg tablets • Eletriptan (Relpax): 40-mg tablets Triptans are contraindicated in pregnancy, cardiovascular disease, complex migraine, and poorly controlled hypertension. Cost is a major factor. Rebound headache can occur with daily use. Side effects include transient pressure sensations in the chest, neck, and head. It is ineffective in TTH and occasionally effective in cluster headache. Insurance coverage varies widely.

Mind-Body Techniques Biofeedback Biofeedback has demonstrated effectiveness in treating both migraine and TTH without major side effects or adverse interactions with other therapies. Thermal biofeedback, in which patients learn to increase the temperature of their hands through guided imagery and relaxation training, and/or electromyography (EMG) biofeedback, wherein patients learn to relax targeted skeletal muscle groups, have been shown to significantly improve migraine symptoms.83,84 A meta-analysis of 25 studies showed that biofeedback is comparable to preventive pharmacotherapy,85 and another meta-analysis of 55 studies revealed that migraine headache frequency and perceived self-efficacy showed strongest improvements in biofeedback patients. Migraine patients experienced significant reductions in headache frequency, intensity, and headache-related disability as well as reductions in interictal symptoms, such as irritation and anxiety, in a study combining thermal and EMG biofeedback and relaxation training.84 Biofeedback, however, did not appear to provide additional benefit in a study involving 64 patients randomized to relaxation training vs relaxation training plus biofeedback.86 Multiple studies showed a reduction in medication use and health service utilization for both migraine and TTH patients when using biofeedback techniques.87,88 Biofeedback may also enhance the effectiveness of preventive, abortive, and rescue migraine medications.89 There are no criteria for predicting benefit from biofeedback, and the training requires a significant time commitment (10- to 15-hour-long sessions plus home practice). Pharmacotherapy combined with biofeedback may have variable results. This is an important point because vascular reactivity (a major target in biofeedback training) may be modified by medications used for headache prevention (e.g., beta-blockers), potentially limiting the effects of training. On the other hand, biofeedback could be favorably synergistic with magnesium or topiramate.90 Biofeedback is indicated in patients intolerant to medications, those oriented toward selfefficacy in pain management, pregnancy, and is especially suited for those willing to regularly practice the techniques.

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Relaxation The category of relaxation includes progressive muscular relaxation, focused breathing exercises, and guided imagery. Holroyd and Penzien reported that these techniques are as effective as biofeedback.55 Treatment effects were enhanced by beta-blockers and other preventive agents, making integration both feasible and effective. Some patients are able to identify the early stages of a headache in time to deploy focused relaxation or guided imagery to abort the full development of pain. D’Souza et al. demonstrated that relaxation training improved headache frequency and disability associated with migraines among college students compared to written emotional disclosure or a neutral writing group control.91 These techniques can be taught in groups and then practiced individually using audiotapes. Relaxation appeals to those with an internal locus of control and above-average motivation (see Chapter 94). Cognitive-Behavioral Therapy Cognitive-behavioral therapy is a stress-management approach designed to help patients identify maladaptive thought patterns (e.g., self-blame, hopelessness, helplessness, worthlessness, and catastrophizing) as well as emotional states such as anger and anxiety that can precipitate and amplify headaches. Acknowledgment of present-moment and historical emotional states, shifting of habitual thought patterns, and modification of physiological responses are the key steps in this approach. It has been shown to be effective, alone or in combination, with other behavioral therapies for headache.92 Combining cognitive-behavioral and biofeedback therapies is effective. Hypnosis Hypnosis has been shown to reduce the number of headache days and decrease headache intensity among patients with chronic TTH.93 For abortive therapy, hypnosis is useful in helping patients identify the early stages of migraine so that they can initiate relaxation or selfhypnosis routines. Patient motivation and regular practice is a vital part of this strategy. Self-hypnosis can also be useful in resetting expectations about future successes with treatment, reducing rumination about the past and future, and modifying patterns of negative thought (see Chapter 95). Mindfulness Meditation Meditation has been shown to have positive effects on mood, cardiac function, blood pressure, and muscle tone when regularly practiced. Effects are believed to be mediated by the development of nonjudgmental awareness of feelings, thoughts, and sensations combined with a sense of gratitude while optimizing the sympathetic and parasympathetic nervous system balance. Group instruction is based on the work of Jon Kabat-Zinn94,95 and is taught as an 8-week course, including 2–3 hours of formal training each week, combined with daily practice of at least half

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an hour of meditation. Patients report improved sleep and less anticipatory anxiety relating to headache as well as reduction in headache intensity.96 Home practice is important in maintaining benefits.97 Feasibility studies indicate that mindfulness training, specifically Kabat-Zinn’s 8-week mindfulness-based stress reduction program, is effective for reducing headache severity in migraine and TTH patients.98,99 One study of migraine patients also showed reductions in levels of anxiety and migraine-related disability after the 8-week course.98 Headache-specific mindfulness training may improve outcomes100,101 (see Chapter 100).

Biomechanical Techniques Physical Therapy Physical therapy alone does not appear to be effective in the treatment of migraine, but it can be useful as an adjunct to biofeedback and relaxation training when there is significant reactive muscle tension in the upper body with limitation of head and neck movement. Spinal Manipulation Chiropractic and osteopathic manipulation approaches are often used for patients whose migraines have a cervicogenic or musculoskeletal component. One study of 218 patients demonstrated comparable results in reduction of migraine headache frequency and intensity in a prospective, randomized, parallel-group comparison of amitriptyline, spinal manipulation, and their combination.102,103 A systematic review of manual therapies for the treatment of migraine included four RCTs, each of which suggested that chiropractic spinal manipulation may have prophylactic effectiveness similar to that of propranolol and topiramate.104 However, many of the studies lacked methodological rigor, necessitating future research. Another review published in the same year found that spinal manipulation, whether performed by a chiropractor, physician, or physical therapist, was not effective as a replacement drug therapy for reducing migraine duration but may be an appropriate adjuvant therapy.105 A review of 21 articles found evidence in support of effectiveness of spinal manipulation for episodic and chronic migraine but not TTH.106

Bioenergetics Acupuncture Findings from a systematic review and meta-analysis of acupuncture for migraine prophylaxis involving 22 trials with 4419 participants suggest that acupuncture is more effective than routine care only, but not more effective than sham acupuncture, and that acupuncture is associated with better outcomes and fewer adverse effects than prophylactic drug treatment.107 A more recent patientlevel data meta-analysis of acupuncture for the management of chronic headache (including chronic migraine) concluded that acupuncture is superior to sham acupuncture and medication therapy in decreasing headache

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intensity and frequency and in improving response rate to treatment.108 A recently published sham-controlled randomized trial reported similar findings among patients with frequent migraine.109 The current evidence clearly suggests that acupuncture is effective as an adjunct to usual care in the treatment of migraine, but the degree to which placebo effects contribute to this efficacy is unknown.

positive results in terms of headache frequency, quality of life, medication use, and health services utilization for 24 months after study completion.76 The first prospective pediatric homeopathy study with 159 children in 12 countries showed significant decrease in the frequency, severity, and duration of migraine attacks and reduced absenteeism from school during 6 months of treatment.110

Homeopathy for Headache Prevention

Therapies to Consider

There are few prospective studies that have evaluated the effectiveness of homeopathy for migraine treatment or prevention. A systematic review of four RCTs and two observational studies found varying results. The observational studies showed significant improvements in homeopathically treated patients with regard to headache intensity, medication usage, and health service utilization.75 Three of the four RCTs produced equivocal results, while the remaining RCT showed significant reduction in headache frequency in the homeopathy group.75 A 2010 study found that patients seeking homeopathic treatment for migraine maintained

Formal evidence of effectiveness of the following treatments in migraine is anecdotal, largely theoretical, empirical, limited, or nonexistent. However, some patients respond favorably to them. Based on their overall safety, they may be considered in an integrated treatment plan. For prevention, consider the following: naturopathy, probiotics, ginkgolide B, tai chi, yoga, craniosacral therapy, and ayurvedic medicine. For acute therapy, consider the following: aromatherapy, Reiki, and therapeutic touch; sleep induction with an oral hypnotic; and lorazepam with haloperidol IV; methylprednisolone IV; and valproic acid.

PREVENTION PRESCRIPTION—MIGRAINE • Identify and avoid environmental factors that consistently lead to headache, e.g., allergens, fluorescent lights, loud noises, fumes, and dust. • Implement a sleep hygiene program using a prebedtime routine that signals a time leading to restorative sleep. Avoid excessive as well as inadequate sleep. • Eliminate foods that lower the threshold for migraine, that is, chocolate, aged and yellow cheese, caffeine, red wine, dark beer, shellfish, and meats processed with nitrates.

• W  ater/fluid intake should be a minimum of 40–60 oz per day for an adult. • Maintain an exercise program: aerobic level activity, minimum 30 minutes, three times a week. • Regularize meals, sleep, exercise, and use of medications for prevention. • Maintain a diary documenting headache frequency and intensity, response to medications, association with major life changes, stress, and changes in physiological states, such as menses, pregnancy, and illness. Share the diary information with caregivers.

THERAPEUTIC REVIEW MIGRAINE PREVENTION Lifestyle • Regular meals and sleep, sleep hygiene, aerobic exercise three times a week, headache calendar, stress management, and avoiding environmental triggers

A

1

A

B

1

• Riboflavin, 200 mg bid

B

1

• Coenzyme Q10, 150 mg daily

• Consider discontinuation of hormonal birth control method if menstrual migraine is evident or the history is suggestive of cause and effect. Consider nonhormonal birth control such as a copper intrauterine device. Nutrition • Elimination of food triggers: wine, aged cheese, cashews, chocolate, processed meats, caffeine

Biochemical Supplements • Magnesium aspartate, 500-1000 mg qhs

1

B

1

Botanicals • Feverfew, 125 mg up to tid

B

2

• Butterbur, 50 mg tid

A

1

• F  or sleep: valerian root extract, 100-300 mg qhs B1; melatonin, 6–10 mg qhs

B

1

Pharmaceuticals • Aspirin, 325 mg daily

C

2

• Amitriptyline, 10–150 mg qhs

A

2

117

12  Headache • Propranolol, 60–180 mg daily

Biochemical Supplements and Herbals • Magnesium sulfate, 2 g IV in 100 mL saline over 30 min

A

2

C

2

A

2

• Ginger tea for nausea, 8 oz q3 h

B

2

• Aromatherapy (peppermint)

A

2

B

1

Pharmaceuticals • Naproxen sodium, 250–500 mg q4 h

Mind-Body • Biofeedback 10 sessions

A

1

• Cognitive behavioral therapy

A

1

• Hypnosis

B

1

B

1

C

2

• Gabapentin, 300–600 qid • Topiramate, 100–200 mg qhs • Verapamil, 180–480 mg daily • Valproate, 500 mg tid • Botulinum toxin, subcutaneous 100 units q3 mo

• Mindfulness meditation 8-wk course Biomechanical Consider in cases where muscle tension in the jaw, neck, or shoulder is prominent: • Chiropractic • Massage Bioenergetics • Acupuncture, 6–8 sessions over 8 weeks, repeat as needed

• Ibuprofen liquid, 200–400 mg q2 h

C

A

1

1

Acute Migraine Treatment • Use of specific abortive measures depends on efficacy, cost, side effects, and ease of administration. Use of narcotics and antiemetics is not covered. Lifestyle • Darkened, quiet environment, maintain hydration, meals if possible, sleep

TENSION-TYPE HEADACHE TTH may exist in a spectrum with migraine, as shown by positive responses to antimigraine agents in some patients, with or without coexisting migraine. History and physical examination suggest intermittent muscle traction of pain-sensitive tendons and connective tissues of the head and neck. Pain is typically bilateral, nonthrobbing, and band-like, with trigger points at the base of the skull, temples, masseters, and forehead. The pain is typically slow in onset and intermittent with little or no nausea or sensory sensitivity. Positive responses to NSAIDs suggest that inflammatory and myofascial influences dominate, with modest secondary contributions from vascular structures. Certain pericranial conditions (e.g., brain tumor and central nervous system infection) can present with features of TTH and little else. It is rare for a vascular headache pattern to be the presenting complaint for such conditions. Warning symptoms and signs that suggest the need for head imaging and other studies are reviewed in the first section of this chapter.

INTEGRATIVE THERAPY There is considerable overlap with migraine in an integrated treatment approach to TTH. Lifestyle issues

C

1

C

1

C

1

B

2

C

2

• L  idocaine 4% liquid, 0.25 mL in each nostril q1 h

C

1

• Isometheptene (Midrin) 2 tablets at onset, then 1 tablet q45 min × three

B

1

A

2

B

2

C

2

C

1

B

1

• T  riptans. Many available. Dosing routines identical: initial dose at the onset of head pain, followed no sooner than 2 hours by a second dose if necessary. Limit 3 doses in 24 hours • Valproate, 1 g IV over 1 h • D  HE-45, 1.5 mg IV over 30 min preceded by promethazine (Phenergan) 20 mg IV Mind-Body • Self-hypnosis training • Practiced biofeedback routine • Relaxation

B

1

Biomechanical • Massage, slow stretch

C

1

Bioenergetic • Acupuncture

B

1

surrounding stress, sleep, exercise, and diet are central to effective management and all need to be reviewed carefully for both the work and home environments. It is important to remember that individuals with baseline TTH may develop conditions that abruptly amplify the pain. Examples include sinus and dental infections, head trauma, refractive errors, glaucoma, cervical disk disease, depression, and occult hypertension. A thorough physical examination may lead to discovery of tender areas and trigger points in the head, neck, or shoulders that promote or sustain head pain. Observation of the patient while sitting, walking, and lying down can provide useful clues to musculoskeletal imbalances. Examination of temporomandibular joints is important in all patients because daytime clenching, nocturnal bruxism, and joint disease can all contribute to the pain of TTH. Patient education in ergonomics, posture, and breathing is often useful in treating TTH. Mind-body approaches can be usefully integrated with conventional therapies. Hypnosis has been shown to reduce the number of headache days and decrease headache intensity among patients with TTH.111,112 One study of 98 patients with TTH found that when given a choice between medication treatment with amitriptyline or hypnotic relaxation, more participants chose hypnotic relaxation and stayed with their choice when given repeated opportunities to switch to amitriptyline therapy. Seventy-four percent

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(74%) of patients in the hypnotic relaxation group and 58% of patients in the medication group had a 50% reduction in the frequency of headaches. TTH patients demonstrated decreased headache frequency after a twice-weekly 6-week mindfulness course.101 A combination of sleep hygiene and regularization of daily schedules is effective in reducing pain in motivated and compliant patients. The botanicals for sleep previously described for migraine can be equally effective for those with TTH. Patients should be strongly encouraged to reduce consumption of sugar, caffeine, and red meat along with increasing omega-3 fatty acids to reduce the sympathetic nervous system activity and to enhance the production of antiinflammatory prostaglandins. Detoxification from unneeded drugs is part of effective TTH management. One often overlooked area is dehydration. Poorly hydrated muscles tend to cramp and contract painfully. Pharmaceuticals have a limited role because of the risk of rebound headache and the tendency to reduce motivation to attend to needed lifestyle adjustments. NSAIDs should be medium- to long-acting and strictly limited to less than 20 doses per week. Muscle relaxants provide limited short-term benefit and tend to lead to psychological dependence and rebound headache. Triptans are rarely effective in TTH. When TTH occurs daily or almost daily without evidence of an underlying organic condition, analgesic rebound headache is likely, especially when there is use of more than a total of 20 doses of analgesics (NSAIDs and opiates), decongestants, muscle relaxants, and caffeine per week. Caffeine consumption, when greater than three drinks a day, should be tapered slowly over 2–3 weeks along with short-acting analgesics. Pain is managed with patient education, biofeedback, r­elaxation, slow-stretch exercises, massage, heat, long-­acting NSAIDs, and lowdose tricyclic antidepressants given at night (10–50 mg amitriptyline or equivalent).

Chiropractic There are few older studies of chiropractic or osteopathic manipulation in TTH. Hoyt et al. reported a 50% reduction in headache severity after a single,

10-minute cervical manipulation session.113 In another study of patients with posttraumatic headache, a 57% reduction in pain intensity and a 64% reduction in analgesic use over a 2-week period was found after two cervical spine manipulation treatments compared with treatment with ice packs.114 Another group found no difference between chiropractic manipulation vs daily amitriptyline at the end of a 6-week course of treatment in patients with chronic TTH. However, patients who received chiropractic manipulation had fewer headaches on follow-up 6 weeks after the end of treatment.115 Finally, an RCT comparing soft tissue therapy plus spinal manipulation vs soft tissue therapy plus placebo laser treatment for episodic TTH did not show a statistical difference in outcomes between the two arms.116 Credible recent studies are lacking.

Acupuncture A three-arm, randomized controlled trial involving 270 patients with TTH demonstrated that a course of up to 12 acupuncture treatments over 8 weeks was associated with significantly improved clinical outcomes compared to no acupuncture but not when compared to a shamacupuncture comparison group.117 A systematic review that included a meta-analysis of data from five trials that compared acupuncture with a sham acupuncture control demonstrated small but statistically significant benefits for treatment response and other clinical outcomes. The authors of the systematic review concluded that “acupuncture could be a valuable nonpharmacological tool in patients with frequent episodic or chronic tension-type headaches.”118

Therapies to Consider—TTH Therapies that promote awareness of mind-body healing connections have the greatest potential for reducing TTH pain. Although evidence supporting the following approaches is sparse, they have proven to be useful in some patients: mindfulness meditation, naturopathy, Reiki, healing touch, magnet therapy, aromatherapy, prolotherapy, tai chi, yoga, traditional Chinese medicine and ayurvedic medicine.

PREVENTION PRESCRIPTION—TTH • N  otice physiological reactions to stressful situations in the home and workplace, especially muscle contraction in the neck and shoulders, breathing patterns, chest sensations, and gastrointestinal responses such as nausea, pain, and diarrhea. • Develop a daily relaxation routine that focuses attention on posture and muscles of the head and neck. • Maintain adequate sleep, regular aerobic exercise, and adequate hydration.

• M  odify the diet to ensure regular consumption or supplementation of omega-3 fatty acids. • Be alert to conditions that may contribute to or intensify muscular head pain, such as sinus or dental infection, jaw clenching, tooth grinding, head thrusting, anxiety, and depression. • Be checked for hypertension at least twice a year. • Consult a physician if symptoms of weakness, loss of sensation, poor coordination, difficulty with speech, fever, or syncope occur with TTH.

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12  Headache

THERAPEUTIC REVIEW—TTH TENSION-TYPE HEADACHE • Emphasis is placed on lifestyle and mind-body techniques and reduced reliance on medication.

• Valerian root, 100–300 mg qhs Pharmaceuticals • Time-contingent NSAIDs • Limit total of NSAIDs, decongestants, and caffeine to less than 20 doses per week

Lifestyle • Stress management, sleep hygiene, nutritional choices, ergonomic awareness, regular aerobic exercise

B

Nutrition • Increase omega-3 fatty acid per diet or supplements. Reduce sugar, caffeine, red meats, tobacco, alcohol

C

1

1

Sleep and Exercise • Sleep hygiene • Aerobic exercise, 30 minutes, three times per week

B

1

B

1

Supplements and Herbals • Melatonin, 6–10 mg qhs

B

B

2

A

2

A

1

B

1

Biomechanical • Manipulative therapy, massage, craniosacral therapy

B

2

Bioenergetic • Acupuncture, 6–10 weekly sessions with follow-up as needed

A

1

Mind-Body • Biofeedback and relaxation training • Stress management, cognitive-behavioral therapy, mindfulness meditation

1

Key Web Resources NIH National Center for Complementary and Integrative Health (NCCIH). Current practice guidelines, ongoing research and research findings relating to pain, including headache. NCCAM home page links to headache management using complementary approaches. NIH National Institute of Neurologic Disorders and Stroke (NINDS) website for diagnostic criteria, treatment information, and recently funded research in headache and pain. The American Migraine Foundation website. Academic Headache Centers, guidelines, American Migraine Patient Registry, and Migraine Awareness in Schools. Mayo Clinic. Comprehensive information website on migraine.

REFERENCES References are available online at ExpertConsult.com.

https://nccih.nih.gov/health/pain/headaches.htm

http://www.ninds.nih.gov/disorders/migraine/migraine.htm http://www.americanmigrainefoundation.org/about-us/armr/ http://www.mayoclinic.org/diseases-conditions/migraine-headache/basics/definition/con-20026358

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