A 30-year-old woman complains that her headaches no longer respond to triptans; instead, they have increased in frequencyand severity. The pain interferes with her ability to work part-time and to take care of her 16-month-old daughter.About 12 years earlier, the patient started having migraine headaches. She had no significant medical history, norwas there any obvious precipitating event. Typically, she had 1 or 2 debilitating headaches a month. These were accompaniedby photophobia, nausea, and vomiting-but not by auras. Oral triptans usually relieved the pain and associatedsymptoms within 1 hour.
THE CASE: A 30-year-old woman complains that her headaches no longer respond to triptans; instead, they have increased in frequency and severity. The pain interferes with her ability to work part-time and to take care of her 16-month-old daughter. About 12 years earlier, the patient started having migraine headaches. She had no significant medical history, nor was there any obvious precipitating event. Typically, she had 1 or 2 debilitating headaches a month. These were accompanied by photophobia, nausea, and vomiting-but not by auras. Oral triptans usually relieved the pain and associated symptoms within 1 hour. After her second child was born 16 months ago, the patient began to experience daily headaches that ranged from 4 to 10 in severity on the pain scale; over the past 6 months, the headaches have worsened. In response, she increased her use of almotriptan from once or twice a week to daily. Recently, she has been taking as many as three 12.5-mg doses of almotriptan a day and adding a 100-mg dose of oral sumatriptan if the pain is particularly severe. The headaches have not responded. During the past month, she has visited the local emergency department 2 or 3 times a week, where she has been treated with increasingly higher dosages of intravenous meperidine to alleviate the pain.
How would you intervene?
Primary care doctor: Why do this patient’s headaches no longer respond to triptans?
Headache specialist: A triptan is appropriate for patients who have no more than 8 migraine attacks in a month and who have no contraindications to triptan use (such as uncontrolled hypertension, history of cardiac or cerebral ischemia, or complicated migraine). However, when a patient uses an immediate-relief medication frequently- sometimes even in anticipation of a headache-a pattern of chronic, refractory, daily headaches known as "rebound headache" can develop. Thus, medications that were once an effective treatment for headaches begin to perpetuate pain rather than relieve it. Over-the-counter analgesics, opioids, butalbital, and caffeine-containing products have all been implicated in the development of rebound headaches. Rebound headache that results from overuse of triptans is becoming increasingly common.
Primary care doctor: What can be done to prevent rebound headache in patients who take triptans?
Headache specialist: When you first prescribe a triptan, educate the patient about the importance of adhering to the recommended dose and frequency of use. I recommend that triptan use be limited to a maximum of 2 times per week, up to 2 doses per migraine attack. The only exception is for patients with menstruation-associated migraines. Randomized, double-blind, placebo-controlled trials have shown that daily use of frovatriptan or naratriptan-starting 2 days before menses and continuing through the end of menses-is effective for prophylaxis of menstruationassociated migraines.1 Studies have also established the safety of repeated triptan use in the treatment of acute menstrual migraine.2
Primary care doctor: For patients such as this woman, whose headaches have become more frequent than 2 times a week and no longer respond to previous dosages of triptans, what intervention would you recommend?
Headache specialist: First, avoid the temptation to prescribe more than the recommended dosage of the triptan (Table), even if the patient insists that triptans are the only agents that effectively relieve his or her migraine attacks. When headaches become more frequent or refractory to current treatment, I recommend referral to a headache specialist.
Primary care doctor: My patient clearly has triptanoveruse rebound headache. How should it be treated?
Headache specialist: Although outpatient management is possible, the most effective and lasting approach is treatment in an inpatient headache unit. After the patient is admitted, intravenous medications to resolve the daily headache pattern can be started. I commonly use an every-6-hours regimen of alternating intravenous ketorolac and intravenous orphenadrine. Dihydroergotamine is contraindicated unless the patient has not taken a triptan within 24 hours of admission. Preventive medications are also usually initiated during hospitalization; these can include tricyclic antidepressants, β-blockers, calcium channel blockers, anticonvulsants, and monoamine oxidase inhibitors. During their hospital stay, patients undergo nutritional and pharmacologic evaluations, and they receive intensive education about biofeedback and nondrug approaches to management of their chronic daily headache.
Primary care doctor: After a rebound headache patient is discharged from the hospital, what medications can be used at home for abortive treatment of migraine attacks?
Headache specialist: Patients can be taught to administer migraine-aborting medications based on the severity of their headaches. For mild to moderate headaches, options include oral orphenadrine, NSAIDs, and combination analgesics. However, to avoid the development of new rebound headaches, advise patients not to use these medications more than 3 days a week. For moderate to severe headaches, options include intramuscular ketorolac or diphenhydramine, as well as subcutaneous or intranasal dihydroergotamine. Triptans may also be reintroduced as migraine-aborting agents, provided the patient has been properly educated about their use before discharge from the hospital. Limit triptans (and dihydroergotamine) to no more than 2 days a week to avoid the rebound phenomenon.
Case 2:MAKING BEST USE OF TRIPTANS TO TREAT MIGRAINEWhat criteria can be used to select among the various triptans?Case 2: A longer-acting triptan (such as frovatriptan or naratriptan) is generally preferable for menstruation-associated migraines. For patients who need immediate relief, a triptan with a shorter half-life is more appropriate; examples include sumatriptan, zolmitriptan, rizatriptan, and the newest additions to the triptan class-almotriptan and eletriptan. When you first prescribe a triptan, have the patient take a test dose in your office so that you can monitor him or her for significant side effects, such as chest tightness and palpitations.
Case 3:MAKING BEST USE OF TRIPTANS TO TREAT MIGRAINEWhat is the most effective route of administration?Case 3: Subcutaneous sumatriptan has the fastest onset of action (between 15 and 30 minutes after administration). The oral formulations of all triptans can require from 1 to 2 hours to take effect. The onset of action of sumatriptan nasal spray is reported to be more rapid than that of the oral formulation; however, patient compliance is an issue. A nasal spray formulation of zolmitriptan is now available; it has a slightly more rapid onset of action than the oral formulation. Whether disintegrating zolmitriptan and rizatriptan have a more immediate onset of action than standard oral formulations is unclear.
Case 4:MAKING BEST USE OF TRIPTANS TO TREAT MIGRAINEWhen is the optimal time for a patient to take a triptan?Case 4: Encourage patients to take triptans as early as possible in the course of a migraine attack-regardless of the route of administration. If a patient has migraine with aura, he should take a triptan immediately at the onset of the aura to attempt to abort the attack before headache develops. If a patient does not experience an aura, it is still important to take a triptan during the earliest phase of symptoms.
Newman L, Mannix LK, Landy S, et al. Naratriptan as short-term prophylaxisof menstrually associated migraine: a randomized, double-blind, placebo-controlledstudy.
Salonen R, Saiers J. Sumatriptan is effective in the treatment of menstrual migraine:a review of prospective studies and retrospective analyses.