Introduction
Headache is a problem that has plagued humans since the beginning of recorded time. It is one of the most common medical complaints and accounts for more than 18 million outpatient visits per year in the United States. More than 1% of physician’s office visits and emergency department visits are primarily for headache. In 1988, the International Headache Society (IHS) published a formal classification system for the diagnosis of headache disorders, which has since been updated and improved (International Classification of Headache Disorders, second edition [ICHD-2]). The IHS classification system ( Box 30.1 ) continues to divide headache into primary and secondary disorders. In a primary headache disorder, headache itself is the illness and no other etiology is diagnosed. In a secondary headache disorder, headache is attributed to an identifiable structural or metabolic abnormality.
Migraine
Migraine without aura
Migraine with aura
Childhood periodic syndromes that are commonly precursors of migraine
Retinal migraine
Complications of migraine
- •
Chronic migraine
- •
Status migrainosus
- •
Tension-Type Headache
Infrequent episodic tension-type headache
Frequent episodic tension-type headache
Chronic tension-type headache
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
Cluster headache
Paroxysmal hemicrania
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing
Other Primary Headaches
Primary stabbing headache
Primary cough headache
Primary exertional headache
Primary headache associated with sexual activity
Hypnic headache
Primary thunderclap headache
Hemicrania continua
New daily persistent headache
Headache attributed to head and/or neck trauma
Headache attributed to cranial or cervical vascular disorders
Headache attributed to nonvascular intracranial disorders
Headache attributed to a substance or its withdrawal
Headache attributed to infection
Headache attributed to a disorder of homeostasis
Headache or facial pain attributed to a disorder of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cranial structure
Headache attributed to a psychiatric disorder
Cranial neuralgias and central causes of facial pain
ICHD-2, International Classification of Headache Disorders, second edition.
Instruments and Scales in Headache
Headaches can severely interfere with daily functioning and productivity. Research has demonstrated that improvement in symptoms and quality of life (QOL) are not perfectly correlated: symptoms may improve, but function may not. Consequently, it is important to embrace instruments that measure QOL. Instruments that assess migraine disability can improve headache care by facilitating physician-patient communication and guiding treatment decisions. Various headache scales are in use. The scales can be divided into two main groups: scales that measure the impact of a single migraine attack (with or without therapy) over a 24-hour period and scales that measure the impact of migraine over a span of weeks or months. The first group of scales has been used in randomized, placebo-controlled trials; they are highly sensitive to acute treatment effects. The second group of scales has been chosen to compare results in randomized trials.
Scales that measure the impact of an acute attack include (1) QOL (Migraine-Specific Quality-of-Life Questionnaire [MQoLQ] and Quality of Life Questionnaire [MSQ Version 2.1]) and (2) headache impact and disability (Headache Needs Assessment [HANA] Survey). Scales that measure long-term impact are (1) QOL (Migraine-Specific Quality-of-Life [MSQOL] Scale), (2) headache impact (Headache Impact Test [HIT], Headache Impact Questionnaire [HimQ], and Henry Ford Hospital Disability Inventory [HDI]), and (3) migraine disability (Migraine Disability Assessment [MIDAS]).
Instruments and Scales in Headache
Headaches can severely interfere with daily functioning and productivity. Research has demonstrated that improvement in symptoms and quality of life (QOL) are not perfectly correlated: symptoms may improve, but function may not. Consequently, it is important to embrace instruments that measure QOL. Instruments that assess migraine disability can improve headache care by facilitating physician-patient communication and guiding treatment decisions. Various headache scales are in use. The scales can be divided into two main groups: scales that measure the impact of a single migraine attack (with or without therapy) over a 24-hour period and scales that measure the impact of migraine over a span of weeks or months. The first group of scales has been used in randomized, placebo-controlled trials; they are highly sensitive to acute treatment effects. The second group of scales has been chosen to compare results in randomized trials.
Scales that measure the impact of an acute attack include (1) QOL (Migraine-Specific Quality-of-Life Questionnaire [MQoLQ] and Quality of Life Questionnaire [MSQ Version 2.1]) and (2) headache impact and disability (Headache Needs Assessment [HANA] Survey). Scales that measure long-term impact are (1) QOL (Migraine-Specific Quality-of-Life [MSQOL] Scale), (2) headache impact (Headache Impact Test [HIT], Headache Impact Questionnaire [HimQ], and Henry Ford Hospital Disability Inventory [HDI]), and (3) migraine disability (Migraine Disability Assessment [MIDAS]).
Scales that Assess Quality of Life
QOL is influenced by environmental, economic, social health–related, spiritual, and political factors. The fundamental domains of instruments that measure QOL include physical, psychological, and social areas. Both generic and disease-specific measures have been used to measure QOL. The most commonly used generic scales are the Medical Outcomes Study (MOS) instrument, which includes the 20-Item Short-Form Health Survey (SF-20), the SF-36, and the SF-12. Other generic QOL scales used in headache studies include the Sickness Impact Profile, the Nottingham Health Profile, and the Psychological General Well Being Index. The specific QOL scales for migraine fall into two broadly defined categories: those that measure QOL in a single migraine attack (MQoLQ and MSQ Version 2.1) and those that measure the QOL over a period of weeks or months (MSQOL).
Migraine-Specific Quality-of-Life Questionnaire
The MQoLQ is a questionnaire that assesses the short-term decrements in QOL associated with acute migraine headache attacks. This questionnaire evaluates QOL impairment in the 24-hour period following the onset of a migraine headache. The questionnaire is self-administered and is completed quickly and easily. The MQoLQ consists of 15 items with five domains: (1) work functioning, (2) social functioning, (3) energy/vitality, (4) migraine headache symptoms, and (5) feelings and concerns. There are three items within each domain. The response option for each of the items is on a 7-point scale, with 1 indicating maximum impairment of QOL and 7 indicating no impairment. Each domain has a maximum score of 21 and a minimum score of 3. The scores were compared between migraine-free and migraine periods. The construct validity of the questionnaire was established by showing that there are significant relationships between subjects’ 24-hour MQoLQ scores and other indices of clinical migraine headache such as headache severity, limitation of activity, number of associated migraine symptoms, global change in migraine symptoms, and migraine duration. The ability of the MQoLQ to capture within-subject change in QOL was evaluated by comparing QOL scores during a “migraine-free” period with MQoLQ scores 24 hours after migraine onset. The MQoLQ should be applicable to all adults suffering from episodic migraine headache. It was designed primarily for use in clinical trials to assess migraine management and to be responsive to subject changes in QOL in the 24 hours following the onset of a migraine headache. The MQoLQ assesses subjective well-being and daily ability to function, in addition to measuring the typical associated symptoms of migraine, such as nausea, photophobia/phonophobia, and head pain. The 24-hour MQoLQ should not be used to measure global QOL between headache episodes.
Quality-of-Life Questionnaire (MSQ Version 2.1)
The MSQ is a disease-specific QOL instrument with three hypothesized scales; it has been developed, tested, and revised. The MSQ (version 2.1) was structured similar to older versions of the MSQ (versions 1.0 and 2.0). The revised 14-item MSQ (version 2.1) consists of 7 items in the role-restrictive dimension that measure the degree to which performance of normal activities is limited by migraines, 4 items in the role-preventive dimension that measure the degree to which performance of normal activities is interrupted by migraines, and 3 items in the emotional function dimension that measure the emotional effects of migraine. The MSQ dimensions had low to modest correlations with the two component scores of the SF-36 and were modestly to moderately correlated with migraine symptoms. The validation was structured in three separate analyses applied to 267 subjects. The MSQ provides clinicians, researchers, and those who fund health care a measurement tool to assess health-related QOL. The questionnaire was designed to be completed quickly and easily in a self-administered form. This study suggested that the mean MSQ (version 2.1) scores 6 to 12 points higher (indicating better QOL).
Migraine-Specific Quality-of-Life Scale
The MSQOL is used to assess a migraine patient’s QOL over a long period (average of 3 weeks). It is a valid and reliable self-administered measure and a useful tool in clinical migraine research. The information that MSQOL provides can add important information about migraine’s impact on QOL and the potential benefits of therapeutic interventions. This questionnaire has 25 items, with each question having four answers. The general format and scoring are 1, very much; 2, quite a lot; 3, a little; and 4, not at all. The total score is then transferred to a scale of 0 to 100, with a higher number representing a better QOL. For the MSQOL, Cronbach’s alpha was 0.92, thus suggesting that the items are tapping into a single concept. The MSQOL has the potential to provide valuable information on a migraineur’s QOL and be a useful adjuvant measure when assessing long-term treatment outcomes.
Scales that Assess Headache Impact and Disability
Headache impairs physical, social, and emotional functioning, but a diagnosis cannot always be made despite the availability of helpful tools. One reason for this is poor patient-physician communication. If the impact that headaches are having on a person’s life can be communicated adequately to the physician, the likelihood of appropriate management will increase. Impact and disability instruments are scored differently and have different interpretations. Generally, the impact is scaled in a positive direction, with higher scores reflecting better QOL (i.e., lower impact). For disability measures, higher scores reflect greater limitation of activity (i.e., higher impact). Measurement of headache-related disability, together with assessments of pain intensity, headache frequency, tiredness, alterations in mood, and cognition, can be used to assess the impact of migraine on sufferers’ lives and on society. The tools currently used for assessing headache impact are the HIT and HIT-6, HimQ, HANA Survey, and HDI or Henry Ford Hospital Questionnaire. These scales, when used properly, can improve communication between patients and physicians, assess migraine severity, and act as outcome measures to monitor treatment efficacy. Impact tools are also used, along with other clinical assessments, to produce an individualized treatment plan. Disability measures assess impairment in role functioning (i.e., reduced ability to function in defined roles, such as paid work). The disability instruments used are the HDI and the MIDAS.
Headache Impact Test
The HIT is a tool that measures headache’s impact on a person’s ability to function on the job, at home, and in social situations. The HIT was developed by the psychometricians who developed the SF-36 health assessment. HIT was designed for greater accessibility (on the Internet at www.headachetest.com and www.amlhealthy.com and as a paper-based form known as HIT-6). HIT-6 is a practical test that consists of six questions. A patient can complete the test in less than 2 minutes. HIT-6 assesses disability over a 4-week period. The range of scores is 36 to 78. Higher scores signify greater impact of disability. A score of 60 or higher indicates a severe impact (the headache stops family, work, school, or social activities), a score between 56 and 59 indicates a substantial impact, a score between 50 and 55 signifies some impact, and a score below 49 denotes no impact. The availability of this test on the Internet, with feedback provided, makes it a useful tool to help headache sufferers understand the burden of their migraines and seek appropriate management.
Headache Impact Questionnaire
The HimQ measures pain and limitations in activity over a 3-month period. This instrument was the precursor to the MIDAS instrument (see disability scales). The HimQ score is derived from four frequency-based questions (i.e., number of headaches, missed days of work, missed days of chores, or missed days of non–work-related activity) and four summary measures of the average experience across headaches (i.e., average pain intensity and average reduced effectiveness when having a headache at work, during household chores, and in non–work-related activity). This scale was validated after assessing the pain and limitations in activity in a population-based sample of 132 migraine headache sufferers enrolled in a 90-day daily-diary study who completed the HimQ at the end of the study. Previous studies of the validity of retrospective pain and disability reporting were mixed. Study participants completed the HimQ in person and then completed daily diaries for 90 days. The HimQ was developed to identify headache sufferers who have the greatest need for medical care. Self-administered questionnaires can adequately capture information to rate pain severity.
Headache Needs Assessment Survey
The HANA questionnaire was designed to assess two dimensions (frequency and bothersomeness) of migraine’s impact. Seven issues related to living with migraine were used as ratings of frequency and bothersomeness. Validation studies were performed in a Web-based survey, a clinical trial responsiveness population, and a retest reliability population. Headache characteristics (e.g., frequency, severity, and treatment), demographic information, and the HDI were used for external validation. The HANA can be used in medical practice groups (e.g., headache centers, managed care groups) as a screening tool to detect potential problems. Scores from the scale are compared before and after treatment to determine the headache’s impact. Primary care physicians could use the HANA to screen patients with migraine for further evaluation. Once identified, those with severe migraine may be candidates for further evaluation and immediate treatment. The HANA has several advantages in that it can (1) select who should be treated, (2) increase productivity by adequately treating headaches, and (3) identify the need for aggressive treatment without the usual slow advancement through stepped-care algorithms. This brief, self-applied questionnaire may be a useful screening tool to evaluate migraine’s impact. The two-dimensional approach to patient-reported QOL allows individuals to weight the impact of both frequency and bothersomeness of chronic migraine (CM) on multiple aspects of daily life.
Henry Ford Hospital Disability Inventory
The HDI is useful in assessing the impact of headache and its treatment on daily living. It is a paper-and-pencil instrument that probes the functional and emotional effects of headache on everyday life. The HDI is a 25-item headache disability inventory, with each item requiring a “yes” (4 points), “sometimes” (2 points), or “no” (0 points) response. Thus, a maximum score of 100 points reflects severe self-perceived headache disability. The scale is easy to complete and simple to score and interpret. The HDI has high internal consistency, reliability, and good content validity; the long-term (2 month) test-retest stability of the HDI was robust. The test-retest reliability for the beta-HDI was acceptable for the total score and functional and emotional subscale scores. Scales of this nature help investigators understand headache’s impact on everyday life. Thus, the HDI can be used to (1) assess the impact of headache on the patient’s daily living, (2) monitor the effect of therapeutic intervention, and (3) plan for a global approach to coping with headache with the patient’s involvement.
Migraine Disability Assessment Questionnaire
The MIDAS questionnaire ( Fig. 30.1 ) was developed to measure headache-related disability and improve doctor-patient communication about the functional consequences of migraine. The questionnaire was based on five disability questions that focus on lost time in three domains: schoolwork or work for pay; household work or chores; and family, social, and leisure activities. This scale can be used by physicians, nurses, pharmacists, and alternative practitioners. It is easy to complete and takes only a few minutes. The MIDAS questionnaire has demonstrated reliability, as reported in two separate population-based studies, one in the United States and one in the United Kingdom, and validity by using a 3-month daily-diary study as the “gold standard.” Scores on the MIDAS are highly correlated with physician judgments about the severity of illness and need for treatment. This instrument is scored as follows: 5 to 10 indicates little or no disability, 10 to 20 indicates moderate disability, and higher than 20 denotes severe disability. The MIDAS questionnaire is an important part of a package of educational, investigative, and therapeutic measures and could play a major role in improving the care of patients with migraine and other types of headache. A randomized, placebo-controlled trial showed that the MIDAS grade provides a basis for selecting initial treatment in stratified care.
Migraine
Migraine is a chronic neurologic disease characterized by episodic attacks of headache and associated symptoms. “Migraine” is derived from the Greek word “hemicrania” (Galen ≈200 A.D). The diagnosis is based on retrospective reporting of headache characteristics and associated symptoms. The revised IHS diagnostic criteria for headache disorders (ICHD-2) provide the criteria for a total of seven subtypes of migraine.
Epidemiology
The prevalence of migraine is similar and stable in Western countries and the United States. Three large-scale population-based studies have been conducted in the United States, one in 1989, one in 1999, and one in 2004. The first American Migraine Study found that the prevalence of migraine was 17.6% in women and 6% in men. Two follow-up studies, the American Migraine Study II and the American Migraine Prevalence and Prevention Study (AMPPS), provided results identical to the first, thus indicating that the prevalence of migraine has been stable in the United States, at least over the last 15 years.
Before puberty, the prevalence of migraine is approximately 4% ; after puberty, it increases more rapidly in girls than in boys. It increases until approximately 40 years of age and then declines. Prevalence is lowest in Asian Americans, intermediate in African Americans, and highest in Caucasians. In the United States, the prevalence of migraine decreases as household income increases.
Migraine decreases sufferers’ QOL. The World Health Organization (WHO) ranks migraine among the world’s most disabling medical illnesses. Approximately 28 million Americans have severe, disabling migraine headaches. Migraine’s cost to employers is approximately $13 billion per year, and annual medical costs exceed $1 billion. Instruments to quantify migraine disability include the MIDAS and the HIT.
Description of the Migraine Attack
The migraine attack can consist of premonitory, aura, headache, and resolution phases. Premonitory symptoms occur in 20% to 60% of migraineurs, hours to days before onset of the headache. They may include psychological, neurologic, constitutional, or autonomic features, such as depression, cognitive dysfunction, and bouts of food craving.
Aura
The migraine aura consists of focal neurologic symptoms that precede, accompany, or (rarely) follow an attack. Aura usually develops over a period of 5 to 20 minutes; lasts less than 60 minutes; can be visual, sensory, or motor; and may involve language or brainstem disturbances. Headache usually follows within 60 minutes of the end of the aura. Patients can have multiple aura types: most patients with a sensory aura also have a visual aura. Simple auras include scotomata (loss of vision), simple flashes (phosphenes), specks, geometric forms, and shimmering in the visual field. More complicated visual auras include teichopsia or fortification spectra (the characteristic aura of migraine), metamorphopsia, micropsia, macropsia, zoom vision, and mosaic vision. Paresthesias are often cheiro-aural: numbness starts in the hand, migrates up the arm, and jumps to involve the face, lips, and tongue. Weakness is rare, occurs in association with sensory symptoms, and is unilateral. Apraxia, aphasia, agnosia, states of altered consciousness associated with déjà vu or jamais vu, and elaborate dreamy, nightmarish, trance-like, or delirious states can occur.
Headache Phase
The median migraine attack frequency is 1.5 per month. The typical headache is unilateral, of gradual onset, throbbing (85%), moderate to marked in severity, and aggravated by movement. Pain may be bilateral (40%) or start on one side and become generalized. It lasts 4 to 72 hours in adults and 2 to 48 hours in children.
Anorexia is common. Nausea occurs in almost 90% of patients, whereas vomiting occurs in about a third. Sensory hypersensitivity results in patients seeking a dark, quiet room. Blurry vision, nasal stuffiness, anorexia, hunger, tenesmus, diarrhea, abdominal cramps, polyuria, facial pallor, sensations of heat or cold, and sweating may occur. Depression, fatigue, anxiety, nervousness, irritability, and impairment of concentration are common. Symptom complexes may be generated by linked neuronal modules.
Formal Diagnostic Criteria
The IHS subdivides migraine into migraine with aura ( Box 30.2 ) and migraine without aura ( Box 30.3 ). To diagnose migraine without aura, five attacks are needed. No single feature is mandatory, but recurrent episodic attacks must be documented. Migraine persisting for more than 3 days defines “status migrainosus.” Migraine occurring 15 or more days per month is called CM by the ICHD-2 ( Box 30.4 ).
- A.
At least 2 attacks fulfilling criteria B to E
- B.
Fully reversible visual and/or sensory and/or speech symptoms but no motor weakness
- C.
Homonymous or bilateral visual symptoms, including positive features (i.e., flickering lights, spots, lines) or negative features (i.e., loss of vision), and/or unilateral sensory symptoms, including positive features (i.e., visual loss, pins and needles) and/or negative features (i.e., numbness)
- D.
At least one of the following:
- 1.
At least one symptom developing gradually over a period of 5 or more minutes and/or different symptoms occurring in succession
- 2.
Each symptom lasting between 5 and 60 minutes
- 1.
- E.
Headache that meets criteria B to D for migraine without aura begins during the aura or follows the aura within 60 minutes
- F.
Not attributed to another disorder
- A.
At least 5 attacks fulfilling criteria B to D
- B.
Headache attacks lasting 4 to 72 hours and occurring less than 15 days/mo (untreated or unsuccessfully treated)
- C.
Headache with at least 2 of the following characteristics:
- 1.
Unilateral location
- 2.
Pulsating quality
- 3.
Moderate or severe intensity
- 4.
Aggravated by or causing avoidance of routine physical activity (i.e., walking or climbing stairs)
- 1.
- D.
During headache at least one of the following:
- 1.
Nausea and/or vomiting
- 2.
Photophobia and/or phonophobia
- 1.
- E.
Not attributed to another disorder
- A.
Headache on 15 or more days per month for at least 3 months
- B.
Patient has had at least 5 attacks fulfilling criteria B to D for migraine without aura (see Box 30.3 )
- C.
On 8 or more days per month for at least 3 months headache has fulfilled C1 and/or C2 below, that is, has fulfilled the criteria for pain and associated symptoms of migraine without aura
- 1.
Has at least 2 of the characteristics in a to d:
- a.
Unilateral location
- b.
Pulsating quality
- c.
Moderate or severe pain intensity
- d.
Aggravated by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)
- a.
And at least 1 of characteristics a or b:
- a.
Nausea and/or vomiting
- b.
Photophobia and/or phonophobia
- a.
- 2.
Treated and relieved by triptans or ergot before the expected development of C1 above
- 1.
- D.
No medication overuse and not attributed to another disorder
Migraine with aura is subdivided into typical aura, prolonged aura, hemiplegic migraine, basilar-type migraine, and migraine with acute-onset aura. The IHS classification now allows the association of aura with other headache types. Prolonged aura lasts from 1 hour to 1 week, and persistent aura lasts for more than 1 week (but resolves); if neuroimaging demonstrates a stroke, a migrainous infarction has occurred.
Migraine Variants
Basilar-type migraine aura is characterized by brainstem symptoms: ataxia, vertigo, tinnitus, diplopia, nausea and vomiting, nystagmus, dysarthria, bilateral paresthesia, or a change in level of consciousness and cognition. It should be considered when patients have paroxysmal brainstem disturbances. Some have suggested that hemiplegic migraine should be diagnosed if weakness is present.
Ophthalmoplegic migraine is due to an idiopathic inflammatory neuritis. There is enhancement of the cisternal segment of the oculomotor nerve, followed by resolution over a period of several weeks as the symptoms resolve.
Hemiplegic migraine can be sporadic or familial. Attacks are frequently precipitated by minor head injury. Familial hemiplegic migraine (FHM) is an autosomal dominant, genetically heterogenous disorder with variable penetration. FHM includes attacks of migraine without aura, migraine with typical aura, and episodes of prolonged aura, fever, meningismus, and impaired consciousness. Headache may precede the hemiparesis or be absent. The onset of hemiparesis may be abrupt and simulate a stroke. In 20% of unselected FHM families, patients have cerebellar symptoms and signs (nystagmus, progressive ataxia). All have mutations in CACNA1A .
Treatment
Migraine varies widely in its frequency, severity, and impact on patients’ QOL. A treatment plan should consider not only the patient’s diagnosis, symptoms, and any coexistent or comorbid conditions but also the patient’s expectations, needs, and goals. Migraine treatment begins with making a diagnosis, explaining it to the patient, and developing a treatment plan that takes into account any coincidental or comorbid conditions. Comorbidity indicates an association between two disorders that is more than coincidental.
Conditions that occur in migraineurs with a higher prevalence than would be expected include stroke, myocardial infarction, angina, patent foramen ovale (aura), epilepsy, Raynaud’s syndrome, and affective disorders (depression, mania, anxiety, and panic disorder). Possible associations include essential tremor, mitral valve prolapse, and irritable bowel syndrome.
Pharmacologic treatment of migraine may be acute (abortive) or preventive (prophylactic), and patients with frequent, severe headaches often require both approaches. Acute treatment attempts to relieve or stop the progression of an attack or the pain and impairment once an attack has begun. It is appropriate for most attacks and should be used a maximum of 2 to 3 days per week. Preventive therapy is given, even in the absence of a headache, in an attempt to reduce the frequency, duration, or severity of attacks. Additional benefits include improving responsiveness to acute attack treatment, improving function, and reducing disability.
Pharmacotherapy for Acute Migraine Headache
Acute treatment can be specific (ergots and triptans) or nonspecific (analgesics and opioids). Nonspecific medications control the pain of migraine and other pain disorders, whereas specific medications are effective for migraine (and certain other) headache attacks but are not useful for non–headache-related pain disorders. Triptans are effective for mild, moderate, and severe migraine attacks.
The choice of treatment depends on attack severity and frequency, associated symptoms, coexistent disorders, previous treatment response, and the medication’s efficacy and potential for overuse and adverse events (AEs). A nonoral route of administration and an antiemetic should be considered when severe nausea or vomiting is present. Injections provide rapid relief. Headaches can be stratified by severity and disability (using the MIDAS or the HIT). Analgesics are used for mild to moderate headaches. Triptans and dihydroergotamine (DHE) are first-line drugs for severe attacks and for less severe attacks that do not adequately respond to analgesics. Patients with moderate or severe headaches and moderate or severe disability (based on the MIDAS) who were stratified to treatment with a triptan did better than patients given aspirin and metoclopramide.
Early intervention prevents escalation and may increase efficacy. Triptans can prevent the development of cutaneous allodynia, and cutaneous allodynia predicts triptans’ effectiveness. Before deciding that a drug is ineffective, at least two attacks should be treated. It may be necessary to add an adjuvant or change the dose, formulation, or route of administration. If the response is inadequate, the headache recurs, or AEs are bothersome, a change in medication may be needed. Limiting acute treatment to 2 to 3 days a week can prevent medication overuse headache (MOH). When headaches are very frequent, early intervention may not be appropriate.
All treatments occasionally fail; therefore, rescue medications (opioids, neuroleptics, and corticosteroids) are needed. They provide relief but often limit function because of sedation or other AEs.
Preventive Treatment
Preventive therapy is given in an attempt to reduce the frequency, duration, or severity of attacks. Additional benefits include improving responsiveness to acute attack treatment, improving function, and reducing disability. Preventive treatment may avert episodic migraine’s progression to CM and result in reductions in health care cost. Silberstein and colleagues retrospectively analyzed resource utilization information in a large claims database. The addition of migraine preventive drug therapy to therapy that consisted of only an acute medication was effective in reducing resource consumption. When the 6 months after the initial preventive medication was compared with the 6 months preceding preventive therapy, office and other outpatient visits with a migraine diagnosis decreased 51.1%, emergency department visits with a migraine diagnosis decreased 81.8%, computed tomography (CT) scans with a migraine diagnosis decreased 75.0%, magnetic resonance imaging (MRI) with a migraine diagnosis decreased 88.2%, and other migraine medication dispensing decreased 14.1%.
Preventive medications reduce attack frequency, duration, or severity. According to the U.S. Headache Consortium Guidelines, as recently revised, indications for preventive treatment include the following:
- •
Recurring migraine that significantly interferes with the patient’s QOL and daily routine despite acute treatment
- •
Failure of, contraindication to, or troublesome AEs from acute medications
- •
Acute medication overuse
- •
Very frequent headaches (>1/wk) (risk for CM or medication overuse)
- •
Patient preference
- •
Special circumstances such as hemiplegic migraine; frequent, very long, or uncomfortable auras; or attacks with a risk for permanent neurologic injury
Prevention is not being used to the extent that it should be. Results from the American Migraine Study I and II and the Philadelphia Phone Survey 2 demonstrated that migraine preventive therapy is underused: only 13% of all migraineurs currently use preventive therapy to control their attacks. In the American Migraine Study II, 25% of all people with migraine, or more than 7 million people, experienced more than three attacks per month, and 53% of those surveyed reported either having severe impairment because of their attacks or needing bed rest. According to the AMPPS, 38.8% of patients with migraine should be considered for (13.1%) or offered (25.7%) migraine preventive therapy.
Preventive medication groups include β-adrenergic blockers, antidepressants, calcium channel antagonists, serotonin antagonists, anticonvulsants, and nonsteroidal anti-inflammatory drugs (NSAIDs). The choice is based on efficacy, AEs, and coexistent and comorbid conditions. The drug chosen is started at a low dose and increased slowly until therapeutic effects develop or the ceiling dose is reached. A full therapeutic trial may take 2 to 6 months. Acute headache medications should not be overused. Women of childbearing potential should be on adequate contraception.
Preventive treatment is often recommended for only 6 to 9 months, but until now no randomized, placebo-controlled trials have been performed to investigate migraine frequency after preventive treatment has been discontinued. Diener and associates assessed 818 migraine patients who were treated with topiramate for 6 months to see the effects of discontinuation of topiramate. Patients received topiramate in a 26-week open-label phase. They were then randomly assigned to continue this dose or switch to placebo for a 26-week, double-blind phase. The mean increase in number of migraine days was greater in the placebo group (1.19 days in 4 weeks, 95% confidence interval [CI] = 0.71 to 1.66, P < 0.0001) than in the topiramate group (0.10, −0.36 to 0.56, P = 0.57). Patients in the placebo group had a greater number of days on acute medication than did those in the topiramate group (mean difference between groups of −0.95, −1.49 to −0.41, P = 0.0007). Sustained benefit was reported after topiramate was discontinued, although the number of migraine days did increase. These findings suggest that patients should be treated for 6 months with the option to continue to 12 months. If headaches are well controlled, medication can be tapered and discontinued. Dose reduction may provide a better risk-to-benefit ratio.
Behavioral and psychological interventions used for prevention include relaxation training, thermal biofeedback combined with relaxation training, electromyography biofeedback, and cognitive-behavioral therapy.
Coexistent diseases have important implications for treatment. In some instances, two or more conditions may be treated with a single drug. If individuals have more than one disease, certain categories of treatment may be relatively contraindicated.
The preventive medications with the best documented efficacy are divalproex, topiramate, and the β-blockers. The choice is based on a drug’s proven efficacy, the physician’s informed belief about medications not yet evaluated in controlled trials, the drug’s AEs, the patient’s preferences and headache profile, and the presence or absence of coexisting disorders. The drug chosen should have the best risk-to-benefit ratio for the individual patient and take advantage of the drug’s side effect profile. An underweight patient would be a candidate for one of the medications that commonly produce weight gain, such as a tricyclic antidepressant (TCA); in contrast, one would try to avoid these drugs and consider topiramate when the patient is overweight. Tertiary TCAs that have a sedating effect would be useful at bedtime for patients with insomnia. Older patients with cardiac disease or patients with significant hypotension may not be able to use TCAs, calcium channel blockers, or β-blockers but could use divalproex or topiramate. Athletic patients should use β-blockers with caution. Medications that can impair cognitive functioning should be avoided when patients are dependent on their faculties.
Comorbid and coexistent diseases have important implications for treatment. The presence of a second illness provides therapeutic opportunities but also imposes certain therapeutic limitations. In some instances, two or more conditions may be treated with a single drug. However, there are limitations to using a single medication to treat two illnesses. Giving a single medication may not treat two different conditions optimally: although one of the two conditions may be treated adequately, the second illness may require a higher or lower dose, and therefore the patient is at risk for the second illness not being treated adequately. Therapeutic independence may be needed should monotherapy fail. Avoiding drug interactions or increased AEs is a primary concern when using polypharmacy. For some patients, a single medication may adequately manage any comorbid conditions. However, this is likely to be the exception rather than the rule. Polytherapy may enable therapeutic adjustments based on the status of each illness. TCAs are often recommended for patients with migraine and depression. However, appropriate management of depression often requires higher doses of TCAs, which may be associated with more AEs. A better approach might be to treat the depression with a selective serotonin reuptake inhibitor or selective serotonin-norepinephrine reuptake inhibitor and treat the migraine with an anticonvulsant. Migraine and epilepsy may both be controlled with an antiepileptic drug, such as topiramate or divalproex sodium. Divalproex and topiramate are the drugs of choice for a patient with migraine and bipolar illness. When individuals have more than one disease, certain categories of treatment may be relatively contraindicated. For example, β-blockers should be used with caution in a depressed migraineur, whereas TCAs or neuroleptics may lower the seizure threshold and should be used with caution in an epileptic migraineur.
Although monotherapy is preferred, it is sometimes necessary to combine preventive medications. Antidepressants are often used with β-blockers or calcium channel blockers, and topiramate or divalproex sodium may be used in combination with any of these medications. Pascual and colleagues found that combining a β-blocker and sodium valproate could lead to increased benefit in patients with migraine previously resistant to either drug alone. Fifty-two patients (43 women) with a history of episodic migraine with or without aura and previously unresponsive to β-blockers or sodium valproate monotherapy were treated with a combination of propranolol (or nadolol) and sodium valproate in an open-label fashion. Fifty-six percent had greater than a 50% reduction in migraine days. This open trial supports the practice of combination therapy. Controlled trials are needed to determine the true advantage of this combination treatment in patients with episodic migraine and CM.
Summary
Migraine is an extremely common neurobiologic headache disorder that is due to increased central nervous system excitability. It ranks among the world’s most disabling medical illnesses. Diagnosis is based on the headache’s characteristics and associated symptoms. The economic and societal impact of migraine is substantial. It affects sufferers’ QOL and impairs work, social activities, and family life. There are many acute and preventive migraine treatments on the market. Acute treatment is either specific (triptans and ergots) or nonspecific (analgesics). Disabling migraine should be treated with triptans. Increased headache frequency is an indication for preventive treatment. Preventive treatment decreases migraine frequency and improves QOL. More treatments are being developed, which provides hope to the many sufferers whose migraines are still uncontrolled.
Chronic Daily Headache
Chronic daily headache (CDH) refers to headache disorders experienced very frequently (15 or more days per month), including those associated with medication overuse (MOH). CDH can be divided into primary and secondary varieties. Primary CDH is not related to a structural or systemic illness. Population-based studies in the United States, Europe, and Asia suggest that 4% to 5% of the general population have primary CDH and that 0.5% have severe headaches on a daily basis. In population samples, chronic tension-type headache (CTTH) is the leading cause of primary CDH. CDH patients account for the greatest number of consultations in headache subspecialty practices. They often overuse medication, which may play a role in initiating or sustaining the pattern of pain. Anxiety, depression, and other psychological disturbances may accompany the headaches.
Once secondary headache (including MOH) has been excluded, frequent headache sufferers are subdivided into two groups based on headache duration. When headache duration is less than 4 hours, the differential diagnosis includes cluster headache, paroxysmal hemicrania, idiopathic stabbing headache, hypnic headache, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome). When headache duration is longer than 4 hours, the major primary disorders to consider are CM (see Box 30.4 ), hemicrania continua (HC), CTTH ( Box 30.5 ), and new daily persistent headache (NDPH). CM, NDPH, and HC are primary CDH disorders that are now included in the second IHS classification. Transformed migraine (TM) is similar but not identical to CM.
Infrequent Episodic Tension-Type Headache (IHS Diagnostic Criteria)
- A.
At least 10 previous headache episodes fulfilling criteria B to E listed below. Number of days with such headache less than 1 day/mo (<12 days/yr)
- B.
Headache lasting from 30 minutes to 7 days
- C.
At least 2 of the following pain characteristics:
- 1.
Pressing or tightening (nonpulsating) quality
- 2.
Mild or moderate intensity (may inhibit but does not prohibit activities)
- 3.
Bilateral location
- 4.
No aggravation by walking stairs or similar routine physical activity
- 1.
- D.
Both of the following:
- 1.
No nausea or vomiting (anorexia may occur)
- 2.
Photophobia and phonophobia are absent or one but not the other is present
- 1.
- E.
Not attributed to another disorder
Frequent Episodic Tension-Type Headache
- A.
At least 10 episodes fulfilling criteria B to E. Number of days with such headache is 1 day/mo and less than 15 days/mo for at least 3 months (≥12 days and <180 days/yr)
- B.
Headache lasting from 30 minutes to 7 days
- C.
At least 2 of the following pain characteristics:
- 1.
Pressing or tightening (nonpulsating) quality
- 2.
Mild or moderate intensity (may inhibit but does not prohibit activities)
- 3.
Bilateral location
- 4.
Not aggravated by walking stairs or similar routine physical activity
- 1.
- D.
Both of the following:
- 1.
No nausea or vomiting (anorexia may occur)
- 2.
Photophobia and phonophobia are absent or one but not the other may be present
- 1.
- E.
Not attributed to another disorder
Chronic Tension-Type Headache (IHS Diagnostic Criteria)
- A.
At least 10 episodes fulfilling criteria B to F. Fifteen or more days/mo with such headache for at least a 3-month period (≥180 days/yr)
- B.
Headache lasting hours or may be continuous
- C.
At least 2 of the following pain characteristics:
- 1.
Pressing or tightening quality
- 2.
Mild or moderate severity (may inhibit but does not prohibit activities)
- 3.
Bilateral location
- 4.
Not aggravated by walking stairs or similar routine physical activity
- 1.
- D.
Both of the following:
- 1.
No more than one of the following: photophobia, phonophobia, or mild nausea
- 2.
No moderate or severe nausea and no vomiting
- 1.
- E.
No medication overuse
- F.
Not attributed to another disorder
IHS, International Headache Society.
CM (see Box 30.4 ) has been called TM. Most patients with this disorder are women, 90% of whom have a history of migraine without aura. Patients often report a process of transformation characterized by headaches that become more frequent over a period of months to years, with the associated symptoms of photophobia, phonophobia, and nausea becoming less severe and less frequent. A pattern of daily or nearly daily headaches often develops that phenomenologically resembles a mixture of tension-type headache (TTH) and migraine. That is, the pain is often mild to moderate and is not always associated with photophobia, phonophobia, or gastrointestinal features. Other characteristics of migraine, including aggravation by menstruation and other trigger factors, as well as unilaterality and gastrointestinal symptoms, may persist. Attacks of full-blown migraine superimposed on a background of less severe headaches occur in many patients. The term TM has been used to refer to this process. The term CM is now being used by the IHS, in part because a history of transformation is often missing.
Drug Overuse And Medication Overuse (Rebound) Headache ( Box 30.6 )
MOH was previously called rebound headache, drug-induced headache, and medication misuse headache. Patients with frequent headaches often overuse analgesics, opioids, ergotamine, and triptans. Although stopping the acute medication may result in the development of withdrawal symptoms and a period of increased headache, subsequent improvement in headache usually occurs. Many primary CDH patients who were withdrawn from ergotamine and analgesics and given no further therapy no longer had daily headaches, although about 40% still had episodic migraine attacks.
