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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.

New Developments in the Management of Migraine and Neuropathic Pain

To provide physicians with current information on new advances in the management and treatment of migraine and neuropathic pain.

This activity is designed for neurologists, particularly those who treat migraine and/or neuropathic pain.

After reading this issue, the participant should be able to:

  • Identify the abortive medications associated with the shortest time to development of overuse headaches.
  • Describe the first and most important step in treating patients with medication overuse headaches.
  • Identify when preventive therapy for migraine should be considered.

This activity has been planned and produced in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education. The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians. The Johns Hopkins School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.

The Johns Hopkins University School of Medicine designates this continuing medical education activity for a maximum of 2 hours in Category 1 credit toward the American Medical Association Physicians' Recognition Award. Each physician should claim only those hours of credit that are actually spent on the educational activity. Credits are available until the expiration date of November 30, 2003.

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, and David R. Cornblath, MD, Professor of Neurology, Johns Hopkins University School of Medicine.

This program is supported by an unrestricted educational grant from Ortho-McNeil Pharmaceuticals, Inc.

Publisher's Note and Disclaimer: The opinions expressed in this issue are those of the authors, presenters, and/or panelists and are not attributable to the publisher, editor, advisory board of Advanced Studies in Medicine, or The Johns Hopkins University School of Medicine or its 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 issue 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.

Advanced Studies in Medicine (ISSN-1530-3004) is published by Galen Publishing, LLC, an HMG Company. P.O. Box 340, Somerville, NJ 08876. (908) 253-9001. Web site: Copyright ©2001 by Galen Publishing, LLC. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. Bulk postage paid at Somerville, NJ Post Office and at additional mailing offices. Advanced Studies in Medicine is a registered trademark of The Healthcare Media Group, LLC. Printed on acid-free paper. BPA Membership applied for December 2000.

The contents of this issue of Advanced Studies in Medicine include highlights from the 10th Congress of the International Headache Society held June 29-July 2, 2001, in New York City.


    David R. Cornblath, MD
    Professor of Neurology
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    • Dr Cornblath reports serving as a consultant to SPRI, OMP-RWJ PRI, Avanir, and DP Clinical; and as a board member for Xenos, Amgen, Schwartz Biosciences, and Acorda.

    Brian E. Mondell, MD
    Medical Director
    Baltimore Headache Institute
    Assistant Professor of Neurology
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    • Dr Mondell reports receiving grant and research support from Abbott, AstraZeneca, GlaxoSmithKline, Merck, Novartis, Ortho-McNeil, Pfizer, Pharmacia & Upjohn, and Vernalis Group, PLC.


    Hans-Cristoph Diener, MD
    Chairman and Professor of Neurology
    Department of Neurology
    University of Essen
    Essen, Germany
    • Dr Diener reports serving as a consultant to AstraZeneca Sweden, UK, and Germany; GlaxoSmithKline UK, USA, and Germany; Pfizer USA, Pfizer USA; Böhringer Ingelheim, BASF, Knoll Germany; Bristol-Myers Squibb Germany; Grƒnenthal Germany; 3M Medica Germany; Pharmacia & Upjohn Sweden; Schering Germany; Allergan UK; Schaper and Brƒmmer Germany; LaRoche Switzerland; Parke-Davis Germany; MSD USA and Germany; Lilly USA; Astra Medica Germany, Bayer Vital Germany; Fresenius Germany; Janssen Cilag Belgium and Germany; Novartis Germany; Sanofi-Synthelabo; UCB Germany; Allmeral Spain; and Johnson & Johnson USA.

    John T. Farrar, MD, MSCE
    Senior Scholar
    Center for Clinical Epidemiology and Biostatistics
    University of Pennsylvania
    Philadelphia, Pennsylvania
    • Dr Farrar reports receiving grant and research support from Pfizer, Cephalon, SmithKline Beecham, Knoll, and Searle; serving as a consultant to Abbott, Alza, and Endo; and serving on the speakers' bureau for Perdue Frederick.

    Steve D. Wheeler, MD
    Director and Co-Founder
    Ryan Wheeler Headache Treatment Center
    Miami, Florida
    • Dr Wheeler reports receiving grant/research support from Ortho-McNeil and GlaxoSmithKline; serving as a consultant to and receiving honoraria from Ortho-McNeil, Pfizer, and GlaxoSmithKline.

Advanced Studies in Medicine provides disclosure information from contributing authors, participating faculty, and presenters only. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Preventing Migraine Headache and Neuropathic Pain:
What is the role of antiepileptic drugs?
Brian E. Mondell, MD ; and David R. Cornblath, MD *

This issue of Advanced Studies in Medicine focuses on the growing use of neuromodulating antiepileptic drugs (AEDs) for migraine headaches and neuropathic pain. This issue contains reports on platform presentations made during the 10th Congress of the International Headache Society (IHC) held June 29 to July 2, 2001 in New York City, including several poster presentations devoted to clinical evaluation of the AEDs for migraine prevention. Also provided in this issue is an interview with a leading neurology researcher who specializes in neuropathic pain. In addition, abstracts of recently published reports involving AEDs in neuropathic pain are included, as well as a case study to illustrate the effects of an AED in a patient with neuropathy.

Advances in our understanding of the pathophysiology for both headache pain and neuropathic pain have provided a sound basis for re-evaluating the established treatment strategies for these common conditions. The AEDs, with their diverse neuropharmacologic actions, are clearly part of this re-evaluation. The availability of advanced-generation AEDs with more favorable side-effect profiles and fewer drug-drug interactions has offered additional incentive for testing these agents as treatment for these common conditions.1,2

Patients with refractory migraine or recurrent head, facial, or other pain related to damaged nerve transmission remain among the most challenging cases seen in neurology practice today. Only rarely does implementation of standard therapy result in the desired degree of relief. More common is the scenario where patients and practitioners exhaust all standard therapy without achieving any meaningful pain relief or improved functional status. These difficult-to-treat patients become frustrated-just as they frustrate the clinicians trying to help them. Some of these patients become lapsed consulters while others switch physicians frequently and get labeled as "difficult or drug seeking." At some point, hopefully, they find their way-either by physician-referral or self-referral-to specialty pain centers. What do these patients really want? They want an understanding physician who will validate their diagnosis and provide them with the most comprehensive information available about the diagnosis including an understanding of the cause of their pain. Of course, they also want-and deserve-the best possible reduction in pain and improvement in ability to function. They need a physician who can help boost coping mechanisms while treating aggressively until the best possible outcome is achieved, someone who they trust will not abandon them.

Will the anticonvulsants help the patient with chronic pain? That is the practical question explored in this issue. While the newer AEDs continue to be tested in a widening range of nonseizure disorders, clinicians must recall that much of the evidence supporting AED use in acute and chronic pain has only been published in recent years.3 In fact, much of the evidence remains nonrandomized and uncontrolled. Still, the preliminary evidence has been promising for AEDs in both migraine prevention and neuropathic pain control.

Migraine Prevention Therapy

Several presentations at the IHC 2001 meeting were devoted to the diagnosis and treatment of patients with the most refractory migraine headaches. Dr Richard Lipton discusses how those who treat frequent headache patients are assisting just the tip of the iceberg. Forty-eight percent of patients with migraine remain undiagnosed; 50% of those diagnosed rely on over-the-counter agents exclusively; and only 29% are very satisfied with their usual acute treatment.4

The ongoing underdiagnosis and undertreatment of individuals, many of whom are in the peak of their working years, has created a burden of $13 billion per year for American employers because of lost workdays and diminished productivity.5 According to Dr Lipton, the portion of patients who are the most disabled by their illness account for 90% of this work loss.4

In this issue, Dr Hans-Cristoph Diener reports on one important segment of this highly disabled population: patients with medication overuse headache. These drug-induced headaches are common in clinical practices specializing in headache treatment and are not uncommon in general neurology practice. In a meta-analysis involving 2612 patients diagnosed with medication overuse headaches, the average individual has had headaches for 10 years and was taking between 2.5 and 5.8 drugs for the headaches. Dr Diener provides valuable insights into the acute agents most likely to produce overuse headaches and outlines the practical steps necessary to withdraw the overused medication and shift to a structured acute therapy with additional preventive therapy aimed at increasing the chances of long-term success.

Dr Steve D. Wheeler reviews recent double-blind placebo-controlled trials with 3 AEDs thought to possess utility in migraine prophylaxis. According to Dr Wheeler, the efficacy of the AEDs is related to their ability to depress neuronal hyperexcitability by acting at gamma-aminobutyric acid receptors and other central nervous system targets. The percentage of patients experiencing a decrease in headache frequency of 50% or more while taking these agents ranges from 16% to 40% with placebo subtracted. Analysis of the adverse-event profiles for the 3 AEDs reviewed-divalproex sodium, gabapentin, and topiramate-shows that they were generally well tolerated. Dr Wheeler concludes that the AEDs are a valuable therapeutic option for migraine headache prevention.

The IHC is a well respected scientific forum for presentation covers the latest research with new therapies. For this reason, this Advanced Studies in Medicine issue also provides summaries of several poster presentations devoted to clinical evaluation of the AEDs for migraine prevention. The consensus conclusion found in most of these retrospective analyses of AED experience-mostly in patients who had already failed on a variety of other preventive agents-is that agents such as levetiracetam, topiramate, and zonisamide are deserving of full double-blind randomized trials that will more exactly define their efficacy and safety profiles.

Several such trials are already under way. Thus, clinicians attending IHC meetings in years to come will undoubtedly find increasingly specific guidance on preventing migraines with AEDs. For those patients with headaches who have the most disabling and frequent headaches, this rapid translation of prevention research findings into clinical practice will bring a new level of control over lives that are now dramatically impaired.

Neuropathic Pain

Neuropathic pain cannot be easily defined, in large part because pain expresses itself differently in different individuals. The pain syndromes may have a very clear diagnosis, such as diabetic neuropathy, or may appear to be caused by muscle pain but do not go away with appropriate treatment for the affected muscles. The latter type can be very difficult to manage, in part because of the difficulty diagnosing the problem. Severe neuropathic pain may be caused by damage to any nerve, not just large ones, and studies may not even show nerve inflammation or damage simply because the affected nerve is so small. Further problems in diagnosing and managing the pain are found with conditions such as referred pain, where finding the source may never be reasonable. The most important aspect of managing neuropathic pain, as well as any type of pain, is that while pain is subjective and the measurement of the pain is based on the patient's perception, it is still a very real entity that can cause tremendous disruption to life if it cannot be adequately managed.

An interview with Dr John T. Farrar gives a candid discussion on neuropathic pain and his findings through research and work with patients on managing this condition. He discusses etiologies, relationships with migraine as well as other diseases, and conventional and unconventional types of treatment. Dr Farrar stresses the importance of each patient receiving individualized treatment, and that when one drug fails, additional ones should be tried until the patient gets a satisfactory degree of relief or until all options have been exhausted. He believes that statistics on high success rates of treatment have less importance in the treatment of neuropathic pain, which can be defined in many ways and has many subtle variations. He uses the example of having a 30% to 40% response rate; while this may not be acceptable for treatment of many diseases, if a drug has the potential to substantially improve the lives of even a small percentage of patients, it should be tried.

The interview includes a detailed discussion on using AEDs, opioids, and other drugs to treat neuropathic pain, as well as other methods of managing pain and related issues. He expresses concern about insurance coverage for affected patients. Because of the uniqueness of each patient's pain and the sometimes unconventional treatments, whether pharmacologic or alternative therapy, insurance coverage is often denied for treatment that actually works on a given patient. While the patient's pain is entirely real, the treatment regimen that works may be too novel for the insurance company to accept.

Dr Farrar discusses resources available to treating physicians, including those available in the community, and gives his thoughts on the multidisciplinary approach found in many clinics. He talks about the role of most neurologists in treating this type of pain, and notes that many neurologists are either inexperienced in this area, lack appropriate knowledge of newer treatments, or choose to send their patients to pain clinics rather than keep trying medications and other therapeutic modalities until relief is achieved. He also provides information on obtaining a certificate in Subspecialization in Pain Management, which is currently available to physicians in a variety of specialties.


1. Delvaux V, Schoenen J. New generation anti-epileptics for facial pain and headache. Acta Neurol Belg. 2001; 101:42-46.
2. Carter GT, Galer BS. Advances in the management of neuropathic pain. Phys Med Rehabil Clin N Am. 2001;12:447-459.
3. Wiffen P, Collins S, McQuay H, et al. Anticonvulsant drugs for acute and chronic pain. Cochrane Database Syst Rev. 2000;3:CD001133.
4. Lipton RB. Epidemiology & impact of headache. Neurology Ambassador's Program. AAN/AHS teaching course held in conjunction with the 10th Congress of the International Headache Society; June 29, 2001; New York, NY.
5. Hu XU, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999;159:813-818.

*Baltimore Headache Institute, Johns Hopkins at Green Spring Station, Lutherville, Maryland; Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland.

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