Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 45th Annual Congress of the Canadian Neurological Sciences Federation

Quebec City, Quebec / June 8-11, 2010

According to a Canadian migraine survey carried out in 2005, 25% of Canadian women and 8% of Canadian men experience migraine. The same survey showed that on average, women with migraine suffer at least partial disability 21 days a year, suggesting that the burden of morbidity associated with migraine in Canada is substantial. The high prevalence of migraine, together with its substantial morbidity, makes advances in the field of headache management all that much more important. Delegates attending the CNSF scientific sessions learned of several such advances made over the past year.

Migraine Prevention Strategies

Migraine prevention is clearly the optimal therapeutic strategy. As discussed by Dr. Werner J. Becker, Professor, Clinical Neurology, University of Calgary, Alberta, for patients who have not received prior prophylaxis, a beta blocker such as propranolol or nadolol is frequently successful; alternatively, multiple studies have shown amitriptyline can provide prophylactic relief and may be particularly useful in patients who have concomitant insomnia or depression.

For hypertensive patients with migraine, beta blockers, the angiotensin II receptor blocker candesartan and the ACE inhibitor lisinopril have all been used with varying degrees of success in migraine prophylaxis. Second- and third-line strategies may involve agents such as topiramate, divalproex and gabapentin, although they can be associated with significant side effects.

Alternatively, a novel migraine prophylaxis approach involving the use of botulinum toxin type A has been shown to reduce headache and migraine frequency and decrease triptan use in men and women with 15 or more baseline headaches occurring over the course of four weeks. At least half of the headache days were migraine days.

At the end of 24 weeks, pooled data from the PREEMPT (Phase II Research Evaluating Migraine Prophylaxis Therapy with Botulinum Toxin Type A) trials indicated that patients (n=688) randomized to the onabotulinum toxin A arm experienced 8.4 fewer headache days and 8.2 fewer migraine days compared with 6.6 and 6.2, respectively, for placebo (n=696) controls. The active treatment group also had 7.7 fewer moderate and severe headache days compared with 5.8 for placebo patients, and triptan use fell slightly more in the active treatment group compared with placebo as well.

There was only one treatment-related serious adverse event, a migraine requiring hospitalization, in the active treatment group compared with none in placebo controls; discontinuation rates due to adverse events were again low at under 4%.

Triptan Efficacy

New research shows that triptans are effective during the migraine aura. A study of 19 patients who were asked to treat eight consecutive attacks found that taking a triptan during the aura pre-empted the development of headaches in 89% of attacks (Aurora SK. Headache 2010;49(7):1001-4). “This study, which is probably the best one so far, certainly indicated that a triptan given during the aura works very well,” Dr. Becker confirmed. He added, “Perhaps this isn’t surprising given that in the clinic, many patients tell us they take their triptan during the aura and find it’s the best for them.” He stated that some studies suggesting triptans are not as effective during aura were relatively small and some involved subcutaneous triptans which rapidly enter the bloodstream, whereas oral triptans are absorbed over time.

Even as mounting research points to the efficacy of triptans, many experts agree these agents are not prescribed often enough; one survey suggested that only 8% of women with migraine take a triptan. “The reasons for this are unknown—it might be that physicians aren’t thinking of these agents, or they think they’re too costly, or that they have too many side effects, which isn’t the case as triptans are very safe for the healthy migraine patient,” said Dr. Becker.

Some physicians here argued that triptans should only be considered later in the headache attack because of their cost and possible side effects, and because about 29% of migraine sufferers are satisfied with their usual treatment. However, other clinicians clearly supported early administration of these agents. “Triptans should be available to all patients with migraine at an early stage,” stated Dr. Suzanne Christie, President, Canadian Headache Society, and Assistant Professor of Medicine, University of Ottawa, Ontario. “They have been shown to be superior to placebo and although more research needs to be done, most patients would probably fit into an early intervention strategy.”

Emerging Therapy Options

For patients in whom triptans are ineffective, delegates speculated that a calcitonin gene-related peptide (CGRP) antagonist presently in investigation holds promise. CGRP is synthesized in trigeminal ganglion cells and is transported to both their central and peripheral nerve terminals, and likely plays a key role in migraine pathophysiology. The hope is that antagonists of CGRP receptors might provide treatment without the vasoconstrictor effects of triptans. Delegates here heard results of a randomized double-blind trial of the oral CGRP receptor antagonist telcagepant. Findings indicated that at 300 mg, it was more effective (P=0.001) than placebo on all primary end points (pain freedom, pain relief and absence of photophobia, phonophobia and nausea, all at two hours’ post-dose) and sustained pain freedom at 150 mg (P=0.05) (Ho et al. Lancet 2008;372(9656):2115-23).

“The CGRP antagonists will be one more option for our patients,” concluded Dr. Becker. “Preliminary data suggest they are not more effective than triptans, but hopefully they will work for many patients in whom the triptans don’t work. They have a different approach and have very few side effects.”

Research on Magnetic Stimulation, Other Advances

Also discussed at the CNSF was whether single-pulse transcranial magnetic stimulation (sTMS) is effective in migraine with aura. The randomized, double-blind, parallel-group, two-phase study (Lipton RB. Lancet Neurology 2010;9(4):373-80) found that pain-free response rates after 2 hours were significantly higher with sTMS (39%) than with sham stimulation (22%), for a therapeutic gain of 17% (95% CI, 3-31%; P=0.0179).

Experts have also sought to determine whether menstrual migraines are worse than non-menstrual migraines. A post-hoc analysis of a multicentre prospective study (MacGregor EA. Headache 2010;50(4):528-38) found that menstrual episodes were more likely to cause impairment, lasted longer, and were more likely to relapse within 24 hours compared to non-menstrual episodes.

Yet another advance is in the understanding of the relationship between migraine and ischemic stroke. Neurologist Dr. Elizabeth Leroux, Centre Hospitalier de l’Université de Montréal, Quebec, told delegates that while migraine without aura is not a risk factor for ischemic stroke, the literature shows migraine with aura does have an association with stroke, albeit a weak one, with a higher risk among women who smoke or take oral contraceptives.

Treatment Gaps in Emergency and Pediatrics

There are still a number of treatment gaps that inhibit optimal headache management. One such gap is in the emergency department (ED). The 1% to 2% of ED visits that are related to headache “may not be considered a vital emergency and may be given less attention” than other cases, remarked Dr. Leroux. “ED doctors have a lot on their minds, and general practitioners are not adequately trained to manage headache, although this should improve when the new Canadian guidelines become available. There is also a lack of specialized headache people; if you consider the prevalence of headache disorders, there should be more headache centres to care for these patients.”

Patients typically come to the ED because they are experiencing an unusual headache, one that is more severe or longer-lasting than their typical attacks. While the goal is to exclude secondary causes and to ensure a proper diagnosis, migraine headache is correctly diagnosed only about half the time in the ED, reported Dr. Leroux. Upon discharge, moderate or severe headache is present in at least 35% and in as many as 50% of patients, depending on the study cited, she noted.

“The priority should be to identify patients who don’t have adequate prescriptions for their usual headaches, to find the chronic daily headache patients—and this is pretty easy to do by asking very simple questions—and to refer them to adequate care.” Another treatment obstacle may be the availability of headache specialists to treat children, despite the prevalence of this condition in youngsters. According to Dr. Joseph Dooley, Professor and Head, Pediatric Neurology, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, 26.6% of 12- to 13-year-old Canadian children and 31.2% of 14- to 15-year-olds report experiencing headaches at least once a week.

It is important to reassure families and physicians that these headaches are not usually indicative of something more serious such as a brain tumour. Moreover, unwarranted investigations can be counter-productive: if nothing is found, they may only serve to further stress the family. “The vast majority of children don’t need investigations,” Dr. Dooley told delegates.

Summary

Headaches are a common phenomenon, even in children, yet experts here at the CNSF agreed that this condition often goes undiagnosed. Important recent advances in headache management include research suggesting that triptans can be effective during aura and that transcranial magnetic stimulation (sTMS) is a viable treatment option. Yet while more treatment options exist now than ever before, treatment gaps still exist, including those in the emergency and pediatric departments.