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TRIPTANS PLAY A LARGER ROLE IN MEDICATION OVERUSE HEADACHE, STUDY FINDS

Triptans can lead to medication overuse headache (MOH) sooner and at lower doses than other acute headache medications, such as ergots and analgesics, a study published in the October issue of Neurology found.

Investigating the pharmacologic features of MOH, a group of neurologists at the University Hospital in Essen, Germany, determined that the mean duration until onset of MOH was 1.7 years for triptan users, 2.7 years for those taking ergots, and 4.8 years for patients taking analgesics. In some patients taking triptans, as few as 10 doses per month caused MOH (Neurology 2002;59: 1011–1014).

Based on the results of this and other studies, the new International Headache Society's (IHS) classification of MOH, to be published in 2003, will incorporate the growing evidence about triptan-induced MOH. (See sidebar, “New Criteria for MOH.”) The IHS had previously defined MOH in 1988 as a constant, diffuse, dull, daily headache, sometimes “pulsating,” without associated autonomic symptoms, which occurs following the overuse of ergots or analgesics for more than 15 days per month for at least three months.

OVERUSE IS PERVASIVE

Commenting on the study, Stephen D. Silberstein, MD, Director of the Jefferson Headache Center at Thomas Jefferson University School of Medicine in Philadelphia, said most people with chronic daily headache overuse acute medications. Neurologist Gretchen E. Tietjen, MD, Director of the Medical College of Ohio's Headache Clinic in Toledo, also reports that most patients she sees with frequent headaches are “using way too many medications.”

MOH has been “a growing problem” worldwide since its description in 1951 by G. A. Peters and B. T. Horton, according to an accompanying editorial in the same issue of Neurology by Dr. Silberstein and K. M. A. Welch, MD, Vice Chancellor for Research at the University of Kansas Medical Center (Neurology 2002;59:972–974). Prevalence of MOH ranges from one to two percent in population-based studies to five to 10 percent in some European headache centers.

STUDY DESIGN

Patients in the study by Drs. Volker Limmroth, Zaza Katsarava, Hans-Christoph Diener, and S. Przywara “originally had migraine or tension-type headache,” said Dr. Diener, Professor of Neurology, by phone from his office in Essen. “Due to medication overuse they had developed daily or almost-daily headaches.”

The investigators recruited 98 patients from their center, who experienced more than 10 headache days per month or who took acute headache drugs more than 10 days per month. Through the use of headache diaries and structured interviews, the patients were divided into groups according to their primary headache: migraine, tension-type, or a combination of the two.

Further subdivisions occurred according to the type of medication being overused. Study participants were then admitted to the hospital for inpatient withdrawal from medications. If they experienced headaches after this point, they were given prednisone and intravenous acetylsalicylic acid (as rescue analgesics), according to Dr. Diener.

The majority of migraine patients overusing triptans developed a migraine-like daily headache or an increase in the number of their migraines. Patients overusing analgesics – who accounted for nearly half of the study population – developed tension-type headaches.

TRIPTAN EFFECT

The study suggests, Drs. Silberstein and Welch write, that “the pharmacological and clinical presentation of triptan-induced MOH is different from other acute headache drugs such as ergots and analgesics.” Therefore, a clinician might suspect triptan-induced MOH when a patient with migraine experiences a frequency in migraine attacks.

The study does not clarify possible causes for triptan-induced MOH, although the editorial writers posit that its pathogenesis may be related to pre-existing dysfunction of the periaqueductal grey matter (PAG) and the propensity of triptans to bind to PAG.

PREVENTING MOH

Without definitive causal explanations, prevention of MOH becomes crucial, said Dr. Silberstein. “The secret is to limit prescriptions to nine tablets per month, two to three days per week, so that the patients don't reach that threshold.”

Dr. Tietjen agrees with Dr. Silberstein's recommendation, but notes that clinicians may sometimes “give patients a double-edged message about the use of triptans. Some data report that the earlier triptans are used in the headache, the more likely they are to abort the headache. But then we tell patients, ‘Don't use too many.’ I do think earlier is better, but how early is too early?

“The saving grace about this emerging data on triptans is the fact that most patients cannot afford triptans out of their own pockets, so they rely on their insurance companies,” Dr. Tietjen continued. “And most insurance companies in the US, for reasons that are fiscally motivated, limit patients to six to nine preparations per month.”

PROMOTE AWARENESS OF MOH

The German study and the new IHS guidelines are important, said Dr. Tietjen, because they promote “awareness of the [MOH] phenomenon.” Dr. Tietjen recalls one woman at her headache clinic voicing surprise that Excedrin could cause her headache – “She had never heard of that until watching a television news show. She thought that taking 20 Excedrin a day was a way to take care of her headache.”

Figure

Dr. Gretchen E. Tietjen said that most patients she sees with frequent headaches are “using way too many medications.”

Clinicians should carefully monitor the type and frequency of a patient's headaches. This is best done by using headache diaries. “The average migraine patient has a couple migraines per month,” noted Dr. Silberstein. “When patients have very frequent headaches, the first thing you have to ask them is, ‘Are you overusing acute medications?’”

WITHDRAWAL STRATEGIES

Once a patient develops MOH, the strategy should be to start a preventive medication and withdraw the overused medication, said Dr. Silberstein. Discontinuing the abortive medication should be the “top priority,” agreed Dr. Tietjen, but she pointed out that the inpatient method described in the study (which included a seven-day hospital stay) would not work in the US due to insurance reimbursement restrictions.

Patients' busy lives would also interfere with such a strategy, Dr. Tietjen continued. Once she has gauged the patient's motivation to withdraw from the MOH-inducing medication, she first tapers the drug dosage, prescribes a preventive medication, and tries to minimize withdrawal symptoms. For instance, for withdrawal from an opioid, a clonindine (Catapres) patch may be prescribed. A “burst and taper” of prednisone might also be used as a “bridging strategy” until the preventive medication starts working. Another inpatient withdrawal strategy, from studies published by Dr. Silberstein and Neil H. Raskin, MD, of the University of California-San Francisco, is to administer intravenous dihydroergotamine mesylate.

PATIENT EDUCATION

Patient education is crucial to good headache management, agreed those interviewed for this article. At the University Hospital in Essen, patients are enrolled in a behavior modification program run by the psychologist in the headache clinic, said Dr. Diener, to help them learn to manage symptoms. Dr. Tietjen's center offers a free class to every new headache patient before the first clinic visit, which explains mechanisms of headaches, nonpharmacologic strategies for preventing them, and the dangers of medication overuse.

Neurologists can play an important role in educating not only their patients, but their primary care colleagues about headache management and MOH, she said. “Strategies should start at the primary care level: medication should be limited, headaches should be monitored by the patient and their health care provider, habit-forming drugs should be avoided whenever possible.” Physicians should also treat co-morbid conditions such as depression and anxiety, which may make patients less likely to overuse migraine medications.

“The education process needs to go on for health care providers and also for patients,” said Dr. Tietjen, “at a time long before that when ‘a headache expert’ is needed. Maybe people wouldn't need headache clinics if they took care of headache at an earlier stage.”

ARTICLE IN BRIEF

  • ✓ A study in the October Neurology journal determined that the mean duration until onset of medication-overuse headaches (MOHs) was 1.7 years for triptan users, 2.7 years for those taking ergots, and 4.8 years for patients taking analgesics.
  • ✓ The new International Headache Society's classification of MOH, to be published in 2003, will incorporate the growing evidence about triptan-induced MOH.
  • ✓ Neurologists who specialize in migraine management suggest that once a patient develops MOH, the strategy should be to start a preventive medication and withdraw the overused medication.
  • ✓ Clinicians should carefully monitor the type and frequency of their patients' headaches by encouraging them to maintain accounts of their bouts in headache diaries.
  • ✓ Neurologists needs to educate their patients, as well as their primary care colleagues about headache management and MOH.

NEW CRITERIA FOR MEDICATION OVERUSE HEADACHE

8.2. Medication Overuse Headache (Diagnostic Criteria):

  • Very frequent headaches (> 15 days/month)
  • Minimum dose required 2 or more days/week (depending on substance) for > 1 month.

8.2.1 Ergotamine overuse:

  • Ergotamine intake > 2 days/week on a regular basis for > 1 month.

8.2.2 Triptans (any formulation) on a regular basis > 3 days/week for > 2 weeks:

  • Triptans may produce an increase in headache frequency in addition to daily headache. Limited evidence suggests that this process may occur sooner than with other acute migraine medications.

8.2.3 Analgesic/opioid overuse (one or more of the following):

  • >3 tablets/day regularly > 4 days/week of non-opioid simple analgesics
  • >2 tablets/day regularly > 3 days/week of analgesics combined with barbiturates or other non-narcotic compounds
  • One or more opioid analgesics on a regular basis > 2 days/week.

Source: International Headache Society; by permission from Stephen D. Silberstein, MD, Chairman, Publications Committee.