Woman With Daily Headaches That Have Become Refractory to Triptans

THE CASE:

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.After her second child was born 16 months ago, the patient began to experience daily headaches that ranged from4 to 10 in severity on the pain scale; over the past 6 months, the headaches have worsened. In response, she increased heruse 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 oforal sumatriptan if the pain is particularly severe. The headaches have not responded. During the past month, she hasvisited the local emergency department 2 or 3 times a week, where she has been treated with increasingly higher dosagesof intravenous meperidine to alleviate the pain.

• Why are triptans no longer effective in this patient?
• How would you intervene?
• What agents are most likely to be effective in aborting future attacks?

THE DIALOGUE:

Primary care doctor:

Why do this patient's headaches nolonger respond to triptans?

Headache specialist:

A triptan is appropriate for patientswho have no more than 8 migraine attacks in a monthand who have no contraindications to triptan use (such asuncontrolled hypertension, history of cardiac or cerebralischemia, or complicated migraine). However, when apatient uses an immediate-relief medication frequently--sometimes even in anticipation of a headache--a patternof chronic, refractory, daily headaches known as "reboundheadache" can develop. Thus, medications thatwere once an effective treatment for headaches begin toperpetuate pain rather than relieve it. Over-the-counteranalgesics, opioids, butalbital, and caffeine-containingproducts have all been implicated in the development ofrebound headaches. Rebound headache that results fromoveruse of triptans is becoming increasingly common.

Primary care doctor:

What can be done to prevent reboundheadache in patients who take triptans?

Headache specialist:

When you first prescribe a triptan, educatethe patient about the importance of adhering to therecommended dose and frequency of use. I recommendthat triptan use be limited to a maximum of 2 times perweek, up to 2 doses per migraine attack. The only exceptionis for patients with menstruation-associated migraines.Randomized, double-blind, placebo-controlled trials haveshown that daily use of frovatriptan or naratriptan--starting2 days before menses and continuing through the endof menses--is effective for prophylaxis of menstruationassociatedmigraines.

¹

Studies have also established thesafety of repeated triptan use in the treatment of acutemenstrual 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 dosagesof triptans, what intervention would you recommend?

Headache specialist:

First, avoid the temptation to prescribemore than the recommended dosage of the triptan(Table), even if the patient insists that triptans are theonly agents that effectively relieve his or her migraine attacks.When headaches become more frequent or refractoryto current treatment, I recommend referral to aheadache specialist.

Primary care doctor:

My patient clearly has triptanoveruserebound headache. How should it be treated?

Headache specialist:

Although outpatient managementis possible, the most effective and lasting approach is treatment in an inpatient headache unit. After the patientis admitted, intravenous medications to resolve the dailyheadache pattern can be started. I commonly use anevery-6-hours regimen of alternating intravenous ketorolacand intravenous orphenadrine. Dihydroergotamine iscontraindicated unless the patient has not taken a triptanwithin 24 hours of admission. Preventive medications arealso usually initiated during hospitalization; these caninclude tricyclic antidepressants, β-blockers, calciumchannel blockers, anticonvulsants, and monoamine oxidaseinhibitors.During their hospital stay, patients undergo nutritionaland pharmacologic evaluations, and they receive intensiveeducation about biofeedback and nondrug approachesto management of their chronic daily headache.

Primary care doctor:

After a rebound headache patient isdischarged from the hospital, what medications can beused at home for abortive treatment of migraine attacks?

Headache specialist:

Patients can be taught to administermigraine-aborting medications based on the severity oftheir headaches. For mild to moderate headaches, optionsinclude oral orphenadrine, NSAIDs, and combinationanalgesics. However, to avoid the development ofnew rebound headaches, advise patients not to use thesemedications more than 3 days a week. For moderate tosevere headaches, options include intramuscular ketorolacor diphenhydramine, as well as subcutaneous or intranasaldihydroergotamine. Triptans may also be reintroducedas migraine-aborting agents, provided the patienthas been properly educated about their use before dischargefrom the hospital. Limit triptans (and dihydroergotamine)to no more than 2 days a week to avoid therebound phenomenon.

References:

REFERENCES:

1.

Newman L, Mannix LK, Landy S, et al. Naratriptan as short-term prophylaxisof menstrually associated migraine: a randomized, double-blind, placebo-controlledstudy.

Headache.

2001;41:248-256.

2.

Salonen R, Saiers J. Sumatriptan is effective in the treatment of menstrual migraine:a review of prospective studies and retrospective analyses.

Cephalalgia.

1999;19:9-16.