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

Abstract

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.