Using Topiramate in the Treatment of Migraine
In the past decade, advances in the headache diagnosis and treatment have revolutionized the field of headache medicine. The American Migraine Study of 19991 demonstrated the astounding number of migraine patients in this country (on the order of thirty million) and also the embarrassing 50% diagnosis rate. Continuing research has elucidated the pathophysiology of migraine2 and, more recently, the concept of central sensitization,3 the process by which migraine may evolve into a continuous process or chronic migraine. The importance of early intervention4 or early treatment of migraine has been demonstrated in studies using numerous triptans by a variety of pharmaceutical companies. The use of triptans, first introduced as imitrex injections in Europe (1989), has significantly improved the immediate treatment of the disorder as can be attested by the great majority of migraineurs who have discovered this therapy.5
The frequent migraine sufferer, however, still may require the use of prophylaxis or preventer-type medications to further improve ‘headache numbers’ and to avoid potential analgesic rebound. The first medications showing significant benefit in migraine prophylaxis appeared in the seventies and included the tricyclic antidepressants and beta-blockers,6 used either together or separately. A long list of prophylaxis medications in various classes have been used since then including the whole gamut of tricyclic antidepressant beyond amitriptyline, a collection of beta blockers beyond propranolol, ARB’s, calcium channel blockers, SSRI’s and SNRI’s, and anticonvulsants. The rest of the list might include a longer list of medications with limited exposure in the literature having claims of headache benefit — such as levetiracetam and Trileptal.7,8
In recent years, topiramate (Topamax®) has assumed the number one position in medications prescribed by neurologists for the treatment of frequent migraine. Primary care has held back and continues to use beta-blockers as their primary first choice.9 As a headache specialist, it has always been the author’s opinion that primary care physicians have tended toward the older traditional choices of treatment, ones which have less issues and complexity. In other words: treatment options that fit better in the context of a busy primary care practice.
The choice of topiramate in the neurological community has been an evolution, particularly derived from all the previous negative experiences with other prophylaxis medications and their major adverse event profiles. It has basically been an escape from mediocrity.10
Which patients should be considered for migraine prophylaxis therapy? Basically, migraine prophylaxis should be considered when all the self-help treatments and abortive therapy have failed to offer sufficient benefit. There is no simple formula for this decision since it depends on multiple factors: number of headaches, severity of headache, and associated symptoms (such as hemiplegia).11,12 The general consensus among neurologists and headache specialists has been that ‘four or five difficult to control headaches a month’ might be sufficient justification to prescribe a daily prophylaxis medication. If these migraines were easily managed with a single Imitrex or Relpax tablet, however, the decision might be to hold off on the prevention treatment. On the other hand, five severe headaches a month—poorly managed with analgesics or triptans—and lasting a day or more apiece would be another matter and completely justify the use of prophylaxis medication. Another indication for migraine prophylaxis would be the association with neurological features such as aphasia or hemiplegia. One episode of this type of phenomenon might justify prophylaxis therapy.
In our clinic, chronic daily headache is also added to the reasons for prophylaxis therapy and includes ‘patient preference’ in the decision making process. One might add one last complexity to this formula, that being the nature of the patient and the doctor. In spite of all the author’s best efforts, there is a small percentage of patients with their own ideas of appropriate therapy. They may refuse any particular form of treatment based on misconceptions or the experience of a distant relative. On the doctor’s side, there may be basic conservatism that resists any complex or new treatment and, at the other extreme, there are some physicians—described by some as overly aggressive—ready to try any new ideas before they’re studied in any way.
It is important to emphasize that adding a prophylaxis medication does not mean withholding required abortive therapy. The patient on topirimate may also be carrying a triptan and promethazine in her blouse pocket, just to be on the safe side.
Which Prophylaxis Medication In Which Patient?
Medications are chosen for prophylaxis in any particular case based on their ‘adverse event profile,’ meaning that their potential side effects make the decision. Efficacy of these medications is less significant as a criterion since the principal choices all have similar documented efficacy (an average of 50% reduction in migraine days). Considering these ‘usual choices’ of preventer medications, there are considerable issues to ponder. First and foremost, the typical patient will be a younger woman, somewhere between 20 and 50. These patients often have low blood pressure, concerns about body weight, desire to exercise, potential for pregnancy, and a disinclination toward sedating or depressing medications.
Whenever possible, it would be reasonable to select a migraine prophylaxis medication that would not interfere with these concerns. It would also be reasonable, whenever possible, to find a treatment that meets other needs such as hypertension or neuropathy. Basically meaning ‘getting two-for-one.’
Evaluating our traditional medication choices, it is immediately apparent why the evolution has been toward topiramate in the neurological community.
Consideration of Topiramate for the Migraine Patient
The recent popularity of Topiramate arose out of the inadequacy of many of our previous choices. The efficacy concerns with the older medications were overshadowed by the adverse event profiles of the drugs. Young to mid-life women—the primary patient population in the headache world—protested about the risk of birth defects, fatigue, exercise intolerance, weight gain, and many other issues. Topiramate appeared to answer many of these concerns, even though it produced its own unique set of side effects. Most of the side effects could be tolerated and were often transient. Topiramate adverse events included parasthesias, memory loss, GI distress, kidney stones, and many other less common issues. A drop-out rate of 10-25% was in line with most of the other preventer drugs used in headache.13