Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.
New and Emerging Therapies in the Treatment of Migraine
To provide physicians with up-to-date information on the prevention and treatment of migraine with a focus on new and emerging therapies such as antiepileptic drugs.
This activity is designed for neurologists, particularly those who treat patients with migraine.
After reading this Special Report, the participant should be able to:
- Describe the role of antiepileptic drugs for the prevention of episodic migraine.
- Define the level of cognitive decline during and immediately after migraine and cluster headache.
- Identify the most important factors that affect quality of life in patients with migraine.
The Johns Hopkins University School of Medicine designates this continuing medical education activity for up to 2 credit hours in Category 1 of the Physician's Recognition Award of the American Medical Association. Each physician should claim only those hours of credit that he or she actually spends on the educational activity. Credits are available until the expiration date of March 31, 2003.
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. This continuing education activity was planned and produced in accordance with the ACCME Essentials and Standards for Commercial Support.
This continuing education activity was produced under the supervision of Brian E. Mondell, MD, Medical Director, Baltimore Headache Institute, and Assistant Professor of Neurology, Johns Hopkins University School of Medicine.
This program is supported by an unrestricted educational grant from Ortho-McNeil Pharmaceutical, Inc.
Publisher’s Note and Disclaimer: The opinions expressed in this Special Report are those of the authors, presenters, and/or panelists and are not attributable to the sponsor or the publisher, editor, advisory board of Advanced Studies in Medicine, or The Johns Hopkins University School of Medicine or Office of Continuing Medical Education. Clinical judgment must guide each professional in weighing the benefits of treatment against the risk of toxicity. Dosages, indications, and methods of use for products referred to in this Special Report are not necessarily the same as indicated in the package insert for the product and may reflect the clinical experience of the authors, presenters, and/or panelists or may be derived from the professional literature or other clinical sources. Consult complete prescribing information before administering.
The contents of this issue of Advanced Studies in Medicine are based, in part, on the 125th Annual Meeting of the American Neurological Association held in Boston, Massachusetts, October 15-18, 2000.
F. Michael Cutrer, MD
Partners Headache Center
Massachusetts General and Brigham and Women's Hospitals
Harvard Medical School
• Dr. Cutrer reports serving on the speakers' bureaus of and the advisory boards for Glaxo SmithKline, Merck, Abbott, Astra Zeneca, and Ortho-McNeil.
Keith R. Edwards, MD*
Western New England Headache and Neurological Research Center
Alzheimer's Diagnostic and Treatment Center
The Neurological Research Center, Inc.
• Dr. Edwards reports no financial or advisory relationship with any corporate organization.
Fumio Gotoh, MD
• Dr. Gotoh reports no financial or advisory relationship with any corporate organization.
John S. Meyer, MD*
Cerebrovascular Research and Biostatistical Laboratories
Veterans Affairs Medical Center
Department of Neurology and Family and Community Medicine
Baylor College of Medicine
• Dr. Meyer reports no financial or advisory relationship with any corporate organization.
Peter St. George-Hyslop, MD, FRCP(C)
Center for Research in Neurodegenerative Diseases
University of Toronto
University Health Network
Toronto, Ontario, Canada
• Dr. St. George-Hyslop reports receiving grant support from Schering, Canada.
Yasuo Terayama, MD; Masahiro Yamamoto, MD; and Masao Honda, MD
Division of Neurology
Yokohama Stroke and Brain Center
• Drs. Terayama, Yamamoto, and Honda report no financial or advisory relationship with any corporate organization.
*Because of the large number of coauthors listed on some of the articles in this issue, Advanced Studies in Medicine offered the authors the option of having only the lead presenters submit disclosure information. Drs. Meyer and Edwards selected this option. The reader shall be advised that coauthors not providing disclosure information above may or may not maintain financial relationships with corporate organizations.
Advanced Studies in Medicine makes every effort to provide the reader with full disclosure information from major contributors. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts or other very brief summaries.
New and Emerging Therapies in the Treatment of Migraine
Brian E. Mondell, MD
This issue of Advanced Studies in Medicine is the third in a series of 3 on migraine. It focuses on data presented during the 125th Annual Meeting of the American Neurological Association held in October 2000 in Boston, Massachusetts.
Among the migraine and headache-related topics presented at poster and plenary sessions were measurements of quality of life and cognitive decline during migraine and other headache attacks and the use of antiepileptic drugs in migraine prophylaxis and in the clinical management of other nonepileptic neurological disorders. Genetics and genomics studies are beginning to show the etiological relationships between seemingly disparate disorders (e.g., migraine and other disorders), which can have therapeutic implications.
Quality-of-life (QoL) measures are becoming important outcomes in migraine management. However, there is no gold standard to measure QoL because of questionable reliability among the currently available assessment tools, and because migraine is often underdiagnosed, undertreated, and comorbid with other disorders. In a presentation, Dr. Yasuo Terayama of the Yokohama Stroke and Brain Center in Yokohama, Japan, described the application of conjoint analysis to measure QoL in patients with migraine. He and his colleagues found that frequency of headache was clearly the most important factor in determining QoL, followed by duration of headache, daily physical functioning, somatic symptoms, enjoyment of life, and daily community activities. Interestingly, his results also suggest that anticipating the next headache negatively affects QoL, further supporting the need for effective prophylactic therapies.
Migraine is associated with significant direct as well as indirect costs including disability at work and home. The level of disability can range from poorer performance to complete dysfunction. Therefore, measures of cognitive decline are important to assess the full impact of migraine and headache disorders on society. Dr. John S. Meyer, of the Veterans Affairs Medical Center and Baylor College of Medicine in Houston, described a 10-year study involving 196 patients, the results of which documented the reversible cognitive decline that accompanies migraine and cluster headache. Cognitive impairments were found to be greater in younger patients and in women in this study, but clinical depression was not a factor. Treatment with serotonin agonists rapidly restored cognitive function. The implication is that these transitory cognitive impairments represent reversible cerebral neuronal dysfunction from deep serotonergic projections.
Preliminary study results using antiepileptic drugs for migraine prophylaxis have been promising. One such drug is topiramate, a broad-spectrum antiepileptic with several potential mechanisms of action involving inhibition of voltage-gated sodium and calcium channels, blocking glutamate release from alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ kainate glutamate receptors, enhancement of gamma-aminobutyric acid (GABA) receptors, and inhibition of carbonic anhydrase types II and IV. Antiepileptic drugs have been investigated for migraine prophylaxis and treatment because of the proposed role of central nervous system hyperexcitability and cortical spreading depression in migraine with aura. Dr. Keith R. Edwards of the Western New England Headache and Neurological Research Center in Bennington, Vermont, presented a pooled analysis of the results of 2 single-center, placebo-controlled trials evaluating the efficacy of topiramate in migraine prophylaxis. In a total of 70 patients with migraine, topiramate produced significant reductions in headache frequency compared with placebo and was well tolerated.
The genetics of migraine and more specifically, the correlation between genotype and phenotype is one of the most exciting topics in migraine and headache research. Clinical geneticists are beginning to identify mutations in single genes that are associated with seemingly disparate diseases. Yet, mutations in any of several different genes can manifest as common clinical symptoms. During a special lecture at a plenary session, Dr. Peter St. George-Hyslop of the University of Toronto provided an overview of phenotype-genotype interrelationships in neurologic disease and described how molecular genetics has led to advances in our understanding of human disease. Among these advances are genotype-phenotype correlations that result in more accurate predictions of disease outcomes, collation of phenotypically dissimilar diseases that arise from mutations of the same gene and could respond to the same therapy, and the ability to distinguish phenotypically similar but etiologically distinct diseases that would probably require different therapies.
Also featured in this issue is an interview with F. Michael Cutrer, MD, Director of the Partners Headache Center at Massachusetts General and Brigham and Women's Hospitals in Boston, and Assistant Professor of Neurology at Harvard Medical School.
Dr. Cutrer discusses his clinical experience in treating patients with various acute and prophylactic therapies for the management of migraine and other headache disorders. In addition, Dr. Cutrer discusses the complex relationship between migraine and depression, offering insight on how they are linked. Dr. Cutrer also addresses the trend toward using antiepileptic drugs for migraine treatment.
As with other areas of scientific research, recent and current investigations of migraine and other forms of headache continue to raise new issues. Similarly, the burgeoning fields of pharmacogenetics and pharmaco-genomics allow clinical researchers to cross disciplines and therapeutic areas by uncovering unexpected commonalities in disease processes and treatments. As these are explored, it is hoped that future investigations will provide answers that will improve treatment and quality of life.