This issue of Advanced Studies in Medicine explores emerging treatments for migraine and other headache disorders with special focus on specific headache patient populations such as the elderly and those otherwise difficult to diagnose or treat. The issue reports on presentations given during the 14th Migraine Trust International Symposium held in London, United Kingdom, September 23-26, 2002, and one presentation from the American Headache Society's Scottsdale Headache Symposium held in Scottsdale, Arizona, November 15-17, 2002. Also included are summaries of several poster presentations involving headache prevalence, impact, diagnosis, and treatment.

Migraine and other chronic headache disorders greatly impact work productivity and quality of life. New research summarized in this issue indicates that headaches cost employers an estimated $23.7 billion annually in lost productivity and that 75% of this cost is due to headaches occurring while employees are at work—not while out sick. Furthermore, a minority (28%) of workers report the most severe headaches, but these headaches account for 70% of the lost productivity time. In addition, another study used the Headache Impact Test (HIT-6) and a quality-of-life scale as well as a migraine severity scale to assess correlation.1 The researchers concluded that the HIT-6 scale was a worthwhile tool to determine the true impact of migraine—particularly in the functional dimension.

Migraine affects up to 8% of women and 18% of men, but most sufferers do not seek medical attention despite the availability of newer treatments with fewer side effects.2,3 In addition, almost half of migraine patients are underdiagnosed or misdiagnosed, creating another barrier to receiving effective treatment.4-6 Results from the Landmark Study using HIT-6 to assess migraine impact and diagnosis by primary care physicians showed that while primary care physicians correctly diagnosed migraine 87% of the time, about 49% of patients who received a diagnosis of nonmigraine headache actually had migraine.

Whereas migraine incidence peaks at age 40 years and declines thereafter, primary headache disorders, including tension-type headache, cluster headache, chronic daily headache, and, especially, hypnic headache, often occur in older individuals.7-9 However, accurate diagnosis and management in this patient population requires a thorough history and investigation so as not to miss any secondary headache disorders. Medication use, overuse, or rebound can influence the presence of headache in the elderly. Giant cell arteritis, lesional headache, and all other secondary headaches must be excluded in these patients. An appropriate treatment plan cannot be initiated without the correct diagnosis and an understanding of any coexisting medical issues.

Emerging Headache Treatments

Anticonvulsants
New research is providing strong evidence that antiepileptic drugs are the current growth industry for migraine prevention. For example, early pilot studies using topiramate showed that the agent is safe and effective in migraine treatment.10,11 The most recent work is a well-conceived and well-executed randomized, placebo-controlled, double-blind study using 1 of 3 doses of topiramate (50 mg, 100 mg, or 200 mg) or placebo for 26 weeks in patients with migraine and migraine with aura. This study showed that both 100- and 200-mg daily doses caused more than one half of the patients to have at least a 50% reduction in migraine periods. Migraine frequency and the number of migraine days were also significantly reduced with topiramate therapy. In a similarly designed trial, researchers found that patients having migraine with aura experienced a more marked reduction in migraine frequency, number of migraine days, and migraine severity with topiramate. In this study, topiramate was also associated with a 41% reduction in photophobia symptoms—an interesting finding. Although this difference was numerically significant, it was not statistically significant.

In smaller, open-label, uncontrolled studies, the anticonvulsants levetiracetam and oxcarbazepine appeared useful for treating refractory migraine, chronic migraine, and tension-type headache. In one study, intravenous levetiracetam was given to 21 patients with refractory migraine who had not responded to other acute treatments. All but 1 patient reported some response. An open-label study using oxcarbazepine as an add-on therapy to existing preventive therapy in patients with refractory migraine or tension-type headache caused a reduction in monthly migraine frequency in some participants. Of those participants who did respond, some were able to discontinue or reduce their prior preventive treatments.

Botulinum toxins
Researchers investigated an intradermal route of delivering botulinum toxins types A (BTX-A) and B (BTX-B) to treat cervicogenic migraine. Patients received either BTX-A or BTX-B intradermally at the site of greater and lesser occipital nerve inlets on the side of the migraine pain. Of those who responded, there was a reduction in migraine frequency, pain, and/or muscular spasm, and the average duration of effect was 12 to 16 weeks.

In another reported study—a retrospective analysis of charts reviewed—intramuscular injections of BTX-A in facial and cervical regions significantly reduced headache frequency and severity in almost two thirds of chronic daily headache patients during the month following injection. Although much more rigorous research is clearly needed, BTX (especially type A) may offer an important treatment option for chronic daily headache patients—particularly those treatment-resistant or narcotic-dependent chronic daily headache patients.

Occipital Nerve Stimulation
There has been increasing interest in occipital nerve blockade or stimulation, particularly for the treatment of refractory chronic cluster headache. Evidence from animal models and several small human trials shows that stimulation of the greater occipital nerve inhibits stimulus-evoked trigeminal activity and that an implantable stimulation device can provide long-lasting cluster pain resolution.12-15 A case study using this technique in refractory cluster headache is included in this issue. Occipital nerve stimulation has also been tried in patients with occipital neuralgia and chronic migraine with good results. Without doubt, further work will be done with this treatment modality, and, with additional quality data, the role of this procedure should become clear over time.