Acute Migraine Treatment
Despite recent advances in the science and treatment of migraine over the past decade, many clinicians have not significantly changed their approach to managing migraine. Nearly 60% of migraineurs continue to use over-the-counter (OTC) remedies exclusively to manage their headaches, despite a rise in the number of physician-diagnosed migraines. Many of these diagnosed patients still report significant suffering, highlighting the need for appropriate migraine treatment in the management of headache patients.
Effective migraine treatment begins with an accurate diagnosis and a thorough understanding of the impact a primary headache has on the patient's daily life. Clinicians should be aware of the use and the effectiveness of previous and current treatments, bearing in mind that both prescription and OTC products have the potential for exacerbating underlying headache patterns. Once a diagnosis is established, it is essential to take the time to explain the condition to patients. Reassuring patients that their headaches are not caused by something life-threatening, such as a brain tumor or an aneurysm, is an important part of the treatment process. Just as important, patients need to know that you know their condition is real and that you are committed to working closely with them to develop a treatment strategy that will help them regain control of their lives. The following 5-step acute treatment strategy is recommended by the Primary Care Network and is endorsed by the National Headache Foundation:
- Identify components of migraine symptomatology that allow for intervention as early as possible in the migraine process.
- Select the best pharmacologic options for each patient.
- Instruct patients in the proper use of their medications.
- Encourage use of a headache diary to monitor treatment and medication usage.
- Provide information resources for patient education.
Patient Involvement
Involving patients in the treatment decision process helps foster solid doctor-patient relationships, improves the chances for compliance, and leads to a more successful outcome. Be sure that patients fully understand and agree with the goals of treatment (see table below). Thoroughly explain the purpose of each part of the treatment plan, the need for follow-up care, and the pros and cons of all available medications. Set realistic expectations—let patients know that although there is no "cure," appropriate treatment can relieve symptoms and improve quality of life.
| US Headache Consortium Goals for Acute Migraine Treatment |
- Treat attacks rapidly and consistently and prevent recurrence
- Restore the patient's ability to function
- Minimize the use of backup and rescue medications
- Optimize self-care and reduce subsequent use of resources
- Be cost-effective in overall management
- Have minimal or no adverse events
|
Early Intervention
Understanding the evolution of the migraine process and the therapeutic phases (see figure 3.1 of the original guideline document) enhances migraine symptom recognition and promotes optimal acute treatment strategies. A migraine headache often begins with mild to moderate pain, similar to the pain of a tension-type headache. As the attack progresses, the features of the headache become more migraine-like. Early intervention--at the onset of the attack--increases the likelihood of successful treatment, including a pain-free response, a reduction in the number of headache recurrences, and improved tolerability of headaches when they do occur.
Stratified Treatment
Individualized acute migraine treatment is based on many factors, including pain intensity, degree of disability, comorbidity, presence of nausea and vomiting, previous treatment(s), and patient preferences. This individualized, or tailored, treatment approach is recommended not just for individual patients, but should also address individual attacks in a single patient. A stratified treatment approach matches treatment to pain intensity and/or disability level. For example, patients with mild to moderate attacks may benefit from the use of nonsteroidal anti-inflammatory drugs (NSAIDs) or combination analgesics, such as aspirin plus acetaminophen plus caffeine, or acetaminophen plus isometheptene plus dichloralphenazone. For patients with more severe pain or disability, use of migraine-specific medication (triptans, ergotamines) is recommended. In general, triptans are better tolerated, easier to administer, and more efficacious than ergotamines. Use of a non-oral triptan or dihydroergotamine (DHE) with or without an antiemetic for migraines presenting early with nausea or vomiting, for rapid escalation of pain (time to peak intensity within 1 hour), and for intractable migraine can be beneficial.
Formulation, dose, and route of administration are also important considerations. Non-oral routes with the addition of an antiemetic are effective if the headaches are accompanied by nausea and/or vomiting. In general, injections are faster and more effective than suppositories and nasal spray. Tablets, although slower-acting and less effective, may be the patient's preferred drug delivery method, especially when the optimal dose is prescribed. Often, to achieve optimal control of a patient's headache pattern providers must prescribe more than one formulation of abortive, or acute, medication.
If the initial treatment fails, a backup medication should be discussed and provided to the patient. For example, if analgesics are used without success, a triptan or an ergotamine could be considered. Similarly, if a triptan or an ergotamine fails, patients may benefit from the use of neuroleptics, parenteral ketorolac, or combination analgesics that contain opioids.
Medication Overuse
A caveat about acute migraine treatment is to avoid headache due to medication overuse or rebound headache. Keep in mind that medication overuse can occur with almost all analgesics, opioids, ergotamines, caffeine, or triptans. Some patients with frequent disabling headaches may overuse their medication, leading to chronic daily headache along with growing dependence on and habituation to the medication. Withdrawal symptoms, including increased headache, are characteristic upon discontinuation of acute medication. In addition, when patients are trapped in a medication-overuse headache pattern, they are refractory to preventive medications. In most cases, headache improvement will occur after an analgesic washout period.
Medication overuse can be avoided by prescribing appropriate doses and limiting acute pharmacologic therapy to less than 2 to 3 days a week on a regular basis. Physicians should warn their patients that medication overuse can lead to chronic daily headache and a host of serious medical conditions, such as gastrointestinal bleeding, liver dysfunction, and kidney disease. Keeping diaries of headache symptoms and medication use may be valuable in preventing this problem.
Rescue Treatment
Rescue treatment connotes an ineffective outcome from abortive treatment and a need for effective symptom relief, with the goal of averting an unscheduled visit to a physician office or hospital emergency department. A treatment plan including a rescue strategy should be discussed and implemented during a routine office visit. Multiple therapeutic agents can be considered in this role, such as judicious use of opioids or corticosteroids. In addition, future attacks might benefit from the addition of combinations of NSAIDs or antidopaminergic drugs or in-office treatment with intravenous (IV) divalproex sodium. If rescue therapy is required on a regular basis--more than twice a month--attempts should be made to find a more effective first-line abortive agent and the patient should be evaluated for prophylactic treatment. Again, patient diaries may be helpful for guidance in tailoring treatment.
Nonpharmacologic Treatment
Nonpharmacologic approaches, which can also be beneficial for acute migraine treatment, are covered extensively elsewhere in Standards of Care (e.g., "Behavioral Interventions for Management of Primary Head Pain" and "Alternative Headache Treatments"). Headache risk factors and triggers, sleep disruption, delaying meals, stress, and occasionally specific foods or beverages or odors should be identified and avoided whenever possible. Nonpharmacologic treatments are often adjunctive to acute treatment, although at times and especially early in the evolution of a migraine they may be effective and may eliminate the need for pharmacologic interventions. Nonpharmacologic treatments commonly employed are relaxation, biofeedback, visualization, extracranial pressure, and cold compresses. Regular exercise, maintaining regular sleep and meal schedules, and practicing overall good health strategies are also an important part of the treatment regimen but are more effective as preventives than as treatments.
Pharmacologic Treatment
Medications used routinely for acute migraine therapy include nonopioid and opioid analgesics, ergotamines, triptans, and combination therapy, or copharmacy. The US Headache Consortium guidelines for acute management of migraine are listed in the tables below. Agents should be chosen on the basis of documented efficacy, patient preferences, side effects, and the presence or absence of coexisting conditions. (See Tables 3.2 and 3.3 in the original guideline document for specific dosages, routes, and clarifications.)
Table: Nonopioid Medications
| MEDICATION |
US HEADACHE CONSORTIUM GUIDELINES |
| COMBINATIONS |
|
| Aspirin 250 mg + acetaminophen 250 mg + caffeine 65 mg |
Group 1: Reasonable first-line treatment choice for mild to moderate migraine attacks or severe attacks that have been responsive in the past |
| Isometheptene mucate 65 mg + dichloralphenazone 100 mg + acetaminophen 325 mg |
Group 2: May be a reasonable choice for patients with mild to moderate headache |
| NSAIDsa |
|
| Acetylsalicylic acid |
Group 1 |
| Celecoxib |
No controlled trials |
| Diclofenac |
Group 2 |
| Flurbiprofen |
Group 2 |
| Ibuprofen |
Group 1 |
| Indomethacin |
No controlled trials |
| Ketoprofen |
No controlled trials |
| Ketorolac |
Group 2 |
| Meclofenamate |
No controlled trials |
| Naproxen sodium |
Group 1 |
a NSAIDs can be combined with migraine-specific therapies
Table: Migraine-Specific Therapy (Triptans and Ergotamines)
| MEDICATION |
US HEADACHE CONSORTIUM GUIDELINES |
| Triptansb |
|
| Almotriptan malate 6.25 mg and 12.5 mg (p.o.) |
Group 1: Reasonable first-line treatment choice for moderate to severe migraine attacks |
| Eletriptan 20 mg and 40 mg |
Group 1a |
| Frovatriptan 2.5 mg |
Group 1a |
| Naratriptan hydrochloride 1 mg and 2.5 mg (p.o.) |
Group 1 |
| Rizatriptan benzoate 5 mg and 10 mg (p.o.) or MLT (orally disintegrating tablet) |
Group 1 |
| Sumatriptan succinate 6 mg subcutaneous (SQ) injection |
Group 1 |
| Sumatriptan intranasal 5 mg and 20 mg |
Group 1 |
| Sumatriptan succinate 25 mg, 50 mg, and 100 mg (rapid-release, p.o.) |
Group 1 |
| Zolmitriptan 2.5 mg and 5 mg (p.o) or ZMT (orally disintegrating tablet) 5 mg Nasal Spray |
Group 1 |
| Ergotaminesc |
|
| Ergotamine tartrate 2 mg sublingual |
Group 3: Inconsistent evidence |
| Ergotamine tartrate 1 mg and caffeine 100 mg (p.o.) |
Group 3 |
| Ergotamine tartrate 2 mg and caffeine 100 mg (per rectum) |
Group 3 |
| Dihydroergotamine 1.0 mg |
Group 1 |
| Dihydroergotamine mesylate (intranasal) |
Group 1 |
Notes to table:
Group 1: Substantial empirical evidence and pronounced clinical benefit
Group 2: Moderate empirical evidence and clinical benefit
Group 3: Conflicting or inconsistent evidence
Group 4: Empirical evidence indicating clinically ineffective
a Using the criteria applied by the US Headache Consortium, the guideline developers anticipated that this grouping would have been assigned had the data been available at the time of the original Guidelines publication.
b Triptans are contraindicated in the presence of uncontrolled hypertension, history of myocardial infarction (MI), ischemic or structural heart disease, cerebrovascular disease, peripheral vascular disease, and basilar or hemiplegic migraine. Triptans should not be used within 24 hours of treatment with ergot-type drugs and other triptan drugs.
c Ergotamines are contraindicated in presence of uncontrolled hypertension, history of myocardial infarction, ischemic or structural heart disease, cerebrovascular disease, peripheral vascular disease, hepatic or renal dysfunction, sepsis, pregnancy, or basilar or hemiplegic migraine. Ergotamines should not be used within 24 hours of triptans and other ergot-type drugs.
Precautions/Contraindications: NSAIDS: ulcer disease, significant hepatic or renal disease.
Precautions/Contraindications: Acetaminophen: hepatic disease.
Precautions/Contraindications: Aspirin: chicken pox, influenza in children or adolescents.
Precautions: Over-the-counter remedies (OTC) for headaches have long been a staple of headache patients in the United States and other countries. Although many headache patients obtain benefit from these agents, the patients may not inform their physicians that they are using them. Because these agents are available without a prescription, patients presume they are without risk of adverse effects or interaction with other medications or have no effect on their headache management program. Eliciting information on their use and providing patient education related to these agents and their proper use in a treatment program are fundamental to good headache practice.
Nonopioid Analgesics
Many patients with mild to moderate headaches will often respond favorably to simple analgesics, such as aspirin or acetaminophen. Sometimes simple analgesics are combined, and analgesics may be formulated with caffeine or other adjuvants. These combinations may offer several advantages, such as enhanced analgesia, reduced side effects because of lower drug doses, and convenience. Some physicians, however, believe that these agents are more likely to lead to overuse and dependence, so their use should be monitored carefully. Still, in most instances, individuals with mild to moderate headaches do not seek medical care for their headaches.
NSAIDs are among the most commonly prescribed medications in the world and should be considered a first-line option for migraine treatment. However, their effectiveness is often limited by their gastric toxicity. Newer-generation NSAIDs, known as cyclooxygenase-2 (COX-2) inhibitors, may offer increased efficacy with a lower risk of gastrointestinal side effects. Adequate doses are necessary to ensure effectiveness. If one NSAID does not provide relief, consider a trial with another before moving on to a different class of drug.
Isometheptene-containing compounds are superior to placebo and because of their relative safety should be considered an appropriate choice for patients with mild to moderate headache.
Opioid Analgesics
Opioid is an inclusive term that refers to all agonists and antagonists with morphine-like activity. Despite considerable controversy surrounding their use, opioids are an effective and commonly prescribed migraine treatment. Partial agonists, such as butorphanol, may have a lower potential for tolerance and dependence, but abuse of these agents still commonly occurs. To minimize the risks of rebound, abuse, and dependence, opioids should be reserved for patients with moderate to severe pain that does not respond to nonopioid agents. Opioids are also appropriate for acute treatment of migraine headaches in patients who cannot tolerate, or have contraindications to, other migraine drugs or who are pregnant.
Oral opioid combinations (e.g., codeine plus aspirin or acetaminophen) may be considered when sedation side effects will not put the patient at risk and the risk for potential abuse has been addressed. Parenteral opioids may be considered for rescue therapy, under supervision, again when sedation side effects will not put the patient at risk and the risk for potential abuse has been addressed.
Opioids should be administered by the most appropriate route for the clinical circumstance, and dosages should be adjusted to account for differences in bioavailability between the oral, parenteral, and rectal routes of administration. Suggested doses are listed in table 3.4 of the original guideline document. General guidelines for opioid usage limit use to no more than 3 days per week, with monthly limits established below maximum-use parameters.
Ergot Derivatives
Ergotamine is an appropriate choice for patients who have moderate to severe migraine that does not respond to analgesics or who experience significant side effects from other migraine medications. Ergotamine tartrate is available as a sublingual preparation, as well as an oral tablet and a suppository when combined with caffeine, which may enhance absorption. Most ergotamine combinations have lower rates of nausea and vomiting than ergotamine alone.
DHE is a weaker arterial vasoconstrictor but almost as potent a venoconstrictor as ergotamine. Like the triptans, DHE is active at the 5-HT1B/1D receptors, but unlike the triptans, DHE also has activity at a variety of other serotonin, adrenergic, and dopaminergic receptors, which may account for its pharmacologic activity. In addition to its use as a nasal spray and an injectable medication for acute migraine headache, repetitive DHE IV has become the mainstay of acute treatment for intractable headache.
Triptans
Collectively, selective 5-HT1B/1D agonists are known as the "triptans." Sumatriptan, the first triptan to be developed and tested, is the most extensively studied drug in the history of pharmacologic migraine treatment. It has been shown to be effective in relieving headache pain, as well as nausea, photophobia, and phonophobia, and in restoring patients' ability to function. Triptans should be considered first-line treatment for most migraine attacks, other than for those that respond to analgesics or combination agents. None of the triptans should be considered for patients with a history of significant ischemic heart disease, Prinzmetal's angina, uncontrolled hypertension, or strictly basilar or hemiplegic migraine. Worldwide experience suggests, however, that the risk of a serious cardiac-related adverse event attributable to triptans is quite low.
The triptans are all available as traditional oral tablets. In addition, 2 of these agents, rizatriptan and zolmitriptan, are found in tablets that dissolve readily in the mouth, which allows the drug to be taken without fluids. Sumatriptan tablets are now available in a rapid-release formulation that is designed to disintegrate quickly. Sumatriptan and zolmitriptan are also available as nasal spray formulations. The use of a nasal spray may prove beneficial in those patients who have early onset of nausea or vomiting with their headaches or where a rapid onset of activity is needed. The gold standard of triptan therapy remains the subcutaneously administered formulation of sumatriptan.
Rational Copharmacy
Rational polypharmacy should be considered in refractory or dissatisfied patients. Rational polypharmacy includes combining a nonopioid analgesic with a triptan or an ergotamine, combining an antiemetic with a nonopioid analgesic or a triptan or an ergotamine, or combining an antiemetic, a nonopioid analgesic, and a triptan or an ergotamine. The combination of metoclopramide with an NSAID or aspirin has been used extensively in Europe and in clinical trials in the United States. Many consider the combination of an NSAID with a triptan to improve pain reduction and decrease recurrence rates. The combination of triptans with ergotamines or other triptans is contraindicated.
