Pharmacotherapy for migraine has been extensively reviewed.90,92-95
The mainstay of acute migraine therapy consists of certain nonspecific agents used for various pain disorders, including headache (eg, aspirin, acetaminophen, nonsteroidal anti-inflammatory drugs), and migraine-specific agents (eg, ergotamine, dihydroergotamine, and the triptans).93
In the stepped-care approach to acute care, treatment is escalated across or within attacks, beginning with simple analgesics. If these agents provide inadequate relief, an analgesic plus an antiemetic or some other combination of medications may be tried. Migraine-specific agents are
reserved for use when simpler, inexpensive treatments have failed.96
The US Headache Consortium guidelines recommend a stratified-care approach in which the choice of agent is guided by frequency and severity of the migraine attack, degree of disability, associated nonheadache symptoms such as nausea, previous response to medications, and presence of any comorbid disorders.90
Medications with the highest quality of evidence of efficacy are aspirin, ibuprofen, butorphanol nasal spray, oral opiate combinations, dihydroergotamine nasal spray, and triptans (injectable, oral, and nasal spray). Migraine-specific agents such as the triptans are recommended for patients with moderate to severe migraines or milder headaches that do not respond adequately to nonsteroidal anti-inflammatory drugs or a combination of medications, such as aspirin, acetaminophen, and caffeine.90,92,93
Health care professionals must be sure that patients know how to use acute medications for migraine correctly and understand that overuse can increase the frequency and severity of headaches and reduce treatment efficacy. Medication overuse can be detected by routinely asking questions. (1) Do you ever take a pill before social events or work meetings or because you are anxious before migraine symptoms start? (2) Do you ever take a pill just in case? (3) Do you use acute treatment 3 or more days a week? (4) In addition to your prescription medications, about how often do you take over-the-counter pain medications?97
Health care professionals should discourage patients from anticipatory use of symptomatic medications and set limits on their use to prevent the development of medication overuse headache. Although the majority of migraineurs take acute medication, almost 40% meet the criteria for preventive treatment.
Preventive therapy is intended to reduce the frequency of attacks or eliminate them, to reduce the cumulative impact of repeated attacks on the patient's HRQoL and level of disability, to improve the efficacy of acute treatment, and, in some patients, to prevent transformation of episodic migraine to chronic migraine.98,99
Preventive therapies are commonly underused in patients who may be appropriate candidates and who may benefit from treatment. In the American Migraine Prevalence and Prevention survey, 43.3% of migraineurs had never used a migraine preventive agent, although among them 32.4% met expert guideline criteria for considering it (13.1%) or being offered it (19.3%).100
One reason for undertreatment of migraine may be health care professionals' lack of awareness of the positive effects of preventive medications on the HRQoL of migraineurs.99
Using the interviewing techniques of AMCS II to determine the number of migraine days and degree of impairment will help physicians decide whether to consider or offer preventive therapy.
Guidelines for determining the need for preventive therapy based on headache frequency and degree of impairment are presented in .100
To facilitate clinical implementation of these guidelines in practice, researchers developed the MPQ-5 (); psychometric testing demonstrated good reliability and validity.101
The MPQ-5 assesses headache frequency, use of acute treatment, headache-related impairment in several domains, and worry and anxiety related to headache. Responses are summed for a total score, which falls into 1 of 3 categories: preventive treatment not indicated, consider preventive treatment, and offer preventive treatment. In addition, each of the 5 questions has individual cutoff scores, which may raise a “yellow flag” or “red flag.” This information should be used as an indicator that the health care professional should gather additional information and consider appropriate treatments. The β-blockers propranolol and timolol and the neuromodulators divalproex sodium and topiramate are approved for migraine prevention in adults.102-105
Percentage of Patients With Headache Frequency and Attack-Related Impairment and Corresponding Need for Preventiona
Migraine Prevention Questionnaire 5 (MPQ-5).
Other agents used for migraine prevention include anti-depressants98,106
and calcium channel blockers; natural products, such as vitamin B2
, botulinum toxin, Petasites
, and coenzyme Q-10, are useful in some patients.99,107
Our focus is on studies of daily activities and HRQoL with medications that have achieved regulatory approval for use in migraine prophylaxis. With the exception of divalproex sodium, for which improvements in HRQoL measures have been reported in adolescents with migraine,108
most studies have been conducted with topiramate. Garcia-Monco et al109
recently compared the effects of preventive therapy with topiramate and nadolol (which is used off-label for migraine prophylaxis) on HRQoL in patients with migraine. Both drugs significantly improved the SF-36 role-physical domain, but the improvement associated with topiramate treatment was greater than that associated with nadolol treatment.
Several placebo-controlled studies have shown topiramate to be effective for migraine prevention in individuals with episodic migraine or chronic migraine.110-114
The adverse events that occurred in at least 5% of patients receiving topiramate (50-200 mg/d) were largely mild or moderate and included paresthesia, fatigue, memory and concentration difficulties, mood problems, infection, and taste perversion.110-114
Topiramate is effective not only in preventing migraine attacks but also in reducing their freqency; such a reduction may be associated with improvements in the daily work, home, and social activities of migraineurs, as determined by an analysis of MSQ, SF-36, and productivity data from placebo-controlled trials.115-118
Diamond et al115
analyzed data from the 3 pivotal topiramate trials. Results of the pooled analysis indicated that topiramate (100 mg/d) was associated with significant improvement compared with placebo in all MSQ domains (role-restrictive, role-preventive, and emotional function).
A prospective analysis of data from the trial by Silberstein et al112
demonstrated that patients treated with topiramate had statistically significant improvements in MSQ role-restrictive domain scores compared with the placebo group (P
=.035 for topiramate, 50 mg/d, and P
≤.001 for topiramate, 100 and 200 mg/d). Topiramate-treated patients (100 mg/d) also had significantly improved role-preventive domain scores compared with the placebo group (P
=.045). Greater improvements were also observed for the SF-36 role-physical and vitality domain scores in patients receiving topiramate compared with the placebo group, but the difference between the 2 groups was not statistically significant.116
In a similar analysis of data from the trial by Brandes et al,110
patients treated with topiramate (50-200 mg/d) had significantly greater improvement in MSQ role-restrictive (P
=.02 for topiramate, 50 mg/d, and P
<.001 for topiramate, 100 and 200 mg/d) and role-preventive (P
=.007 for topiramate, 50 mg/d; P
=.001 for topiramate, 100 mg/d; and P
=.002 for topiramate, 200 mg/d) domain scores compared with individuals receiving placebo. Statistically greater improvement was also observed in SF-36 role-physical domain scores in the topiramate, 100 and 200 mg/d, groups (P
=.02 vs placebo). The differences in the SF-36 vitality domain scores were not statistically significant between the topiramate-treated and placebo-treated groups, although greater improvements were observed in patients receiving topiramate.117
Dahlöf et al119
assessed the longitudinal effect of topiramate on daily activities and function in the 3 pivotal topiramate trials analyzed by Diamond et al.115
The investigators examined patients' MSQ and SF-36 scores at weeks 8, 16, and 26 of the double-blind phase of each trial, the time points at which the MSQ and SF-36 were given. Compared with the placebo group, patients treated with topiramate (100 mg/d) had significantly improved mean scores for all 3 domains of the MSQ and at all 3 time points (P
<.001 for all except role-preventive [P
=.024 at week 8]). In addition, topiramate-treated patients (100 mg/d) had significant improvements in 7 of the 8 subscores (not role-emotional) of the SF-36 at week 26 compared with patients receiving placebo. Specifically, topiramate treatment was associated with significant improvements in the physical component summary scores throughout the double-blind phase of the trial (P
<.001) and in the mental component summary scores at week 26 (P
A multicenter, randomized, double-blind, placebo-controlled trial by Dodick et al120
studied the effect of topiramate, 100 mg/d, on migraine-related disability, emotional distress, daily activities, and global impression of change in individuals with chronic migraine. The percentage of patients whose MIDAS scores reflected a greater than 50% improvement in migraine-related disability from baseline was higher in the topiramate group than in the placebo group, but these differences were not statistically significant (P
=.074). The MSQ scores (last item carried forward) were significantly improved in patients receiving 100 mg/d of topiramate compared with the placebo group at week 4 in all 3 domains (role-restrictive, role-preventive, and emotional function) and at weeks 8 and 16 in role-restrictive and emotional function (P
<.05). The percentage of patients who reported improvement in the Subject's Global Impression of Change scale score was significantly higher in the topiramate treatment group than in the placebo treatment group (75% vs 61%, respectively; P
=.025). Findings were similar for the Physician's Global Impression of Change scale scores (72% for topiramate vs 59% for placebo; P
Workplace productivity has been evaluated in a post hoc analysis of pooled data from 2 randomized, double-blind, placebo-controlled topiramate trials. Lofland et al118
found that the number of hours worked with migraine, the decreased effectiveness caused by migraine (presenteeism), and total lost productivity (absenteeism and presenteeism) were significantly reduced in the group of patients treated with topiramate (100 mg/d) compared with the placebo-treated group.
Several nonpharmacological interventions have demonstrated empirical efficacy for headache management. As a result, they have become standard components of specialty headache centers and multidisciplinary pain management programs and are endorsed by the US Headache Consortium,121
which consists of several professional agencies, including the American Headache Society, the American Academy of Neurology, and the National Headache Foundation.122
Empirically validated effective nonpharmacological interventions may play an important role in both the acute and the preventive phases of the comprehensive headache management plan and may be offered individually or in conjunction with pharmacotherapy. These interventions offer the benefit of being cost-effective without the potential for drug interactions or adverse effects. Nonpharmacological treatments are useful for patients who need to avoid medication, such as women who are pregnant or trying to become pregnant.123
Also, non-pharmacological therapy may augment the effectiveness of other treatments or minimize the need for their use.124
Several factors, including obesity, depression, anxiety, and stressful life events, have been established as common comorbidities of migraine with bidirectional influences.125,126
Therefore, treating any of the conditions listed previously may also benefit migraine and vice versa.
Headache is a multifaceted disorder that can affect all aspects of patients' lives. Multidisciplinary treatment approaches are often the most effective for the management of headache.127-129
Multidisciplinary headache and pain programs typically involve a range of pain specialists, which may include physicians, nurses, psychiatrists, psychologists, physical therapists, occupational therapists, and social workers, among other health care professionals. For health care professionals who have no multidisciplinary staff, appropriate referrals may be necessary. For more information about finding specialists and making referrals, see the study by Buse and Andrasik.130
Nonpharmacological treatments of migraine include cognitive behavioral therapy, biobehavioral training (ie, biofeedback, relaxation training, and stress management), physical therapy, education, and lifestyle modification or healthy lifestyle training.131
Cognitive behavioral therapy is an empirically tested method that helps patients identify behaviors that may increase or maintain headaches (eg, triggers, stressors, unhealthy lifestyle or habits) and maladaptive or dysfunctional thoughts (ie, cognitions) regarding their headaches.132
Cognitive behavioral therapy can aid in headache management by making patients more aware of triggers, including the association between stress and headache, and identifying and challenging counterproductive or self-defeating beliefs and ideas. Cognitive behavioral therapy is also effective in managing depression, anxiety, panic disorder, obsessive-compulsive disorder, eating disorders, sleep disorders, and other common comorbidities in patients with headache. Patients should work with a licensed psychologist, psychiatrist, or social worker with experience in treating patients with headache or chronic medical conditions. More information about cognitive behavioral therapy can be found on the Association for Behavioral and Cognitive Therapies Web site (www.abct.org).
Biofeedback entails learning to increase awareness of involuntary physiologic functions and bring them under voluntary control, especially functions related to sympathetic arousal, including improving circulation (measured by increasing finger temperature) and reducing muscle tension.133,134
Members of the Association for Applied Psychophysiology and Biofeedback (www.aapb.org) are certified to conduct biofeedback training, but many qualified professionals practice biofeedback therapy without being certified or belonging to this organization. A list of practitioners can be found at the Web site of the Biofeedback Certification Institute of America (www.bcia.org/directory/membership.cfm). Alternatively, patients may work with a licensed psychologist, social worker, physical therapist, or occupational therapist with biofeedback expertise. A list of psychologists with their specialties and location may be obtained through the American Psychological Association.
Relaxation techniques are taught to help patients minimize their physiologic response to stress, decrease sympathetic arousal, and engage the parasympathetic nervous system. Relaxation training is typically conducted by psychologists or other mental health or allied pain professionals but can be self-taught by patients through training manuals or audio or visual relaxation aids. Relaxation training may include diaphragmatic breathing, visual imagery, meditation, prayer, yoga, self-hypnosis, guided relaxation CDs or audiocassettes, and other methods of calming the mind and body. These techniques require regular practice to become effective habitual responses.134,135
Patient education is important for effective headache management. Patients should be well informed about the identification and avoidance of triggers and how to make healthy lifestyle choices. In general, the best advice for migraineurs is to maintain a regular and healthy lifestyle, especially during times when they are most vulnerable to an attack. Healthy lifestyle habits include a regular sleep-wake schedule, regular meals, a diet that avoids processed and unhealthy food, regular exercise, avoidance of excessive caffeine or alcohol consumption, and smoking cessation. Regular practice of stress management and relaxation techniques and self-care should be encouraged. Migraine is also a unique condition in that patients make most of the therapeutic decisions on their own. After a physician prescribes the medication, the patient decides which attacks to treat, when to treat them, how to treat them, the level of adherence, whether to make healthy lifestyle changes, and many other decisions that are central to effective management. Trials of educational interventions have demonstrated significant reductions in pain frequency, intensity, and duration; improved functional status and quality of life; reduced depression; and decreased service utilization (in terms of patient visits to both primary care physicians and the emergency department).136