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Implications of Current Clinical Trials Focused on Medication Overuse and Therapeutic Prophylaxis


  • Funding Statement: This supplement is developed from the content presented during a symposium held at the 52nd Annual Scientific Meeting of the American Headache Society®.

  • Jointly sponsored by the Annenberg Center for Health Sciences and CogniMed Inc.

  • This activity is supported by an independent educational grant provided by Allergan, Inc.

  • Conflict of Interest: Sheena K. Aurora, MD, has received grants and research support from Advanced Bionics Corporation; Alexza Pharmaceuticals, Inc.; Allergan, Inc.; GlaxoSmithKline; MAP Pharmaceuticals, Inc.; Merck & Co., Inc.; Neuralieve Inc.; and Ortho-McNeil Pharmaceutical, Inc.; and has served as a consultant for Allergan, Inc.; GlaxoSmithKline; MAP Pharmaceuticals, Inc.; Merck & Co., Inc.; Neuralieve Inc.; Ortho-McNeil Pharmaceutical, Inc.; and Pfizer Inc. She has received honoraria from GlaxoSmithKline; Merck & Co., Inc.; Ortho-McNeil Pharmaceutical, Inc.; and Pfizer Inc.

S.K. Aurora, Swedish Neuroscience Institute – Swedish Headache Center, 1101 Madison, Suite 200, Seattle, WA 98104, USA, email:


(Headache 2011;51;S2:93-100)

Chronic migraine (CM) is a complex disorder requiring a multifaceted management approach encompassing lifestyle modification, trigger avoidance, behavioral therapy, pharmacotherapy, patient education and support, management of expectations, and close follow-up. The lack of pharmacotherapies approved by the US Food and Drug Administration (FDA) hinders CM prophylaxis and management. Topiramate, gabapentin, tizanidine, fluoxetine, amitriptyline, and onabotulinumtoxinA have been evaluated for prophylactic treatment of CM in randomized, double-blind, placebo-controlled or active comparator-controlled trials. Additional well-designed, placebo-controlled studies are needed to assess the effectiveness of new and existing treatment options for CM. Understanding current clinical trial design and management guidelines is critical to designing future trials that overcome the challenge of consistent use of sensitive and clinically meaningful outcome measures.

Topiramate is approved for episodic migraine management and has been studied for CM management. A growing body of evidence has shown it to be safe, effective, and well-tolerated in specific patient populations. However, intolerable adverse effects and inadequate efficacy associated with topiramate may lead to poor adherence. The efficacy, safety, and tolerability of onabotulinumtoxinA have been demonstrated in studies in various migraine patient populations, leading to recent FDA approval of onabotulinumtoxinA for the prophylactic treatment of CM in adults. These studies included patients with or without medication overuse, which may affect 30% to 80% of CM patients in the USA. In this program, we will analyze and discuss recent clinical trials investigating topiramate and onabotulinumtoxinA for CM.