The U.S. Headache Consortium guidelines for preventive therapy of migraine identify three goals of preventive therapy: (1) a reduction in the frequency, severity and duration of attacks; (2) an improvement in the patient's responsiveness to treatment of acute attacks; and (3) an improvement in the patient's function and a reduction in disability from migraine attacks. According to the guidelines, the decision to institute preventive therapy may be guided by the following factors: (1) the presence of recurrent migraines that interfere with the patient's daily routine despite treatment of the acute attacks; (2) frequent headaches; (3) contraindications to acute therapy; (4) failure or overuse of acute therapy; (5) adverse effects from acute therapy; (6) the cost of acute and preventive therapies; (7) the patient's preference; and (8) the presence of uncommon migraine conditions, including hemiplegic migraine, basilar migraine, migraine with prolonged aura or migrainous infarction (to prevent neurologic damage, as based on expert consensus).
As with the other sections of the U.S. Headache Consortium migraine guidelines, the section on preventive therapy was developed after analysis of data from hundreds of clinical trials on the prevention of migraine. The members of the consortium noted that data from trials of preventive therapy are limited by the diversity of endpoints in the trials, the use of loose criteria to define migraine in early trials, the high dropout rates inherent in long-term studies and the lack of a placebo arm in most comparative trials of two or more treatments. In addition, many of the studies of preventive therapy were poorly performed or reported, making analysis of the data difficult.
Analysis of the Evidence on Preventive Therapy
The members of the consortium reviewed data from clinical trials of alpha2 agonists, anticonvulsants, antidepressants, beta blockers, calcium channel antagonists, non-steroidal anti-inflammatory drugs (NSAIDs), serotonergic agents, hormone therapy, and vitamins and minerals. Individual drugs were categorized according to their clinical efficacy, significant adverse events, safety profile and clinical experience. There were five categories, ranging from group 1 drugs, which were determined to have a high efficacy for the prevention of migraine and mild to moderate adverse events, to group 5 drugs, which were drugs with limited or no efficacy in the prevention of migraine. The accompanying table provides a list of the drugs in each of the five categories of clinical efficacy.
General Principles of Preventive Therapy
The U.S. Headache Consortium formulated general principles of preventive therapy based on consensus of the group. The general principles are as follows:
Medication use—Initiate therapy with the lowest effective dose. Begin with a low dose of the drug and increase the dose slowly until clinical benefits are achieved in the absence of adverse events or until adverse events limit the dose.
Give each treatment an adequate trial. Evidence of clinical benefit may take as long as two to three months. Avoid medications that may interfere with efficacy of preventive therapy, such as overuse of drugs (e.g., ergotamine) used in acute therapy. A long-acting formulation may improve compliance.
Patient education—Maximize compliance. Discuss with the patient the rationale for a particular treatment, when and how to use it and the possible adverse events. Address the patient's expectations. Discuss the expected benefits of therapy and how long it will take to achieve them. Create a formal management plan.
Evaluation—The patient should maintain a headache diary. By consensus, the consortium members consider a headache diary the gold standard for the evaluation of headache attacks. The diary should be user-friendly and should provide information on the frequency, severity and duration of attacks, disability, response to treatment and adverse effects of medication.
Reevaluate therapy, and after a period of stability, consider tapering or discontinuing therapy.
Coexisting conditions—The guidelines recognize that some conditions are more common in patients with migraine. Take into account the presence of coexisting disorders, including stroke, myocardial infarction, Raynaud's phenomenon, epilepsy, affective disorders and anxiety disorders. Coexisting conditions may offer or limit treatment opportunities. If a coexisting condition has been identified, select a drug that will treat both disorders. Establish that the coexisting condition is not a contraindication for the selected migraine therapies. For example, beta blockers are contraindicated in patients with asthma. Establish that the therapy used for a coexistent condition does not exacerbate migraine. Beware of interactions between agents used for migraine and those used for other conditions.
Direct special attention to women who are pregnant or want to become pregnant. Preventive drugs may have teratogenic effects. If treatment is absolutely necessary, select a drug with the lowest risk of adverse effects to the fetus.
Recommendations for Nonpharmacologic Therapy
The U.S. Headache Consortium also analyzed data on the use of various nonpharmacologic therapies in the prevention of migraine. According to the guidelines, such approaches may be well suited for patients who have exhibited a poor tolerance or poor response to drug therapy, who have a medical contraindication to drug therapy, and who have a history of long-term, frequent or excessive use of analgesics or other acute medications. Nonpharmacologic intervention may also be useful in patients with significant stress or in patients who are pregnant, are planning to become pregnant or are nursing.
Members of the headache consortium reviewed data on behavioral therapies such as relaxation training, hypnotherapy, biofeedback training and cognitive-behavioral therapy. In addition, studies of physical treatments were analyzed. Physical treatments included acupuncture, transcutaneous electrical nerve stimulation (TENS), occlusal adjustment, cervical manipulation and hyperbaric oxygen.
The level of the evidence in support of a particular intervention was classified into three categories: Grade A, which indicated multiple well-designed randomized clinical trials relevant to the recommendation and yielding consistent findings; Grade B, which indicated some evidence in support of the recommendation but the evidence was not optimal; and Grade C, which signified that the U.S. Headache Consortium arrived at a consensus on the recommendation but there were no data from relevant randomized controlled trials.
The treatment recommendations for nonpharmacologic therapies are as follows:
Findings: According to the guidelines, relaxation training, thermal biofeedback combined with relaxation training, electromyographic (EMG) biofeedback and cognitive-behavioral therapy are somewhat effective in preventing migraine. On the basis of the evidence reviewed, no conclusions could be made regarding the equivalence or superiority among the behavioral therapies.
Recommendations: Relaxation training, thermal biofeedback combined with relaxation training, EMG biofeedback and cognitive-behavioral therapy may be considered as treatment options for prevention of migraine (Grade A recommendation).
Findings: Behavioral treatments have been directly compared and integrated with drug treatment as preventive therapy for migraine. Studies have shown that propranolol confers additional benefits when added to regimens of thermal biofeedback plus relaxation plus cognitive-behavioral therapy; thermal biofeedback and relaxation; and EMG biofeedback. Amitriptyline also has shown beneficial effects when combined with behavioral therapy.
Recommendations: Relaxation techniques and biofeedback may be combined with preventive drug therapy (i.e., propranolol or amitriptyline) to achieve additional clinical improvement (Grade B recommendation).
Findings: Evidence pertaining to the treatment of migraine with acupuncture is limited and the results are mixed. Similarly, limited evaluation has been conducted on hypnosis, TENS, cervical manipulation, occlusal adjustment and hyperbaric oxygen.
Recommendations: Evidence-based treatment recommendations are not possible for the use of hypnosis, acupuncture, TENS, cervical manipulation, occlusal adjustment and hyperbaric oxygen (Grade C recommendation).