@article{3bc994e294b2480f8382cb19373564a7,
title = "Randomized, placebo-controlled trial of propranolol added to topiramate in chronic migraine",
abstract = "Objective: To assess the efficacy and safety of adding propranolol to topiramate in chronic migraine subjects inadequately controlled with topiramate alone. Methods: This was a double-blind, placebo-controlled, randomized clinical trial conducted through the National Institute of Neurological Disorders and Stroke Clinical Research Collaboration, expected to randomize 250 chronic migraine subjects inadequately controlled (10 headaches/ month) with topiramate (50-100 mg/day) to either propranolol LA (long acting) (240 mg/day) or placebo. Primary outcome was 28-day moderate to severe headache rate reduction at 6 months (weeks 16 to 24) compared with baseline (weeks -4 to 0). Results: A planned interim analysis was performed after 48 sites randomized 171 subjects. The data and safety monitoring board recommended ending the trial after determining that it would be highly unlikely for the combination to result in a significant reduction in 28-day headache rate compared with topiramate alone if all 250 subjects were randomized. No safety concerns were identified. At study closure, 191 subjects were randomized. The 6-month reduction in moderate to severe 28-day headache rate and total 28-day headache rate for combination therapy vs topiramate alone was not significantly different: 4.0 vs 4.5 days (moderate to severe 28-day headache rate; p = 0.57) and 6.2 vs 6.1 days (total 28-day headache rate; p = 0.91). Conclusions: This study does not provide evidence that the addition of propranolol LA to topiramate adds benefit when chronic migraine is inadequately controlled with topiramate alone. Classification of evidence: This study provides Class II evidence that propranolol LA, added to topiramate, is ineffective in chronic migraine patients who fail topiramate monotherapy.",
author = "Silberstein, {S. D.} and Dodick, {D. W.} and Lindblad, {A. S.} and K. Holroyd and M. Harrington and Mathew, {N. T.} and D. Hirtz",
note = "Funding Information: Dr. Silberstein serves on scientific advisory boards for AGA Medical Corporation, Allergan, Inc., Amgen, Boston Scientific, CAPNIA, Coherex Medical, CoLucid Pharmaceuticals, CyDex Pharmaceuticals, Inc., GlaxoSmithKline, Eli Lilly and Company, MAP Pharmaceuticals, Inc., Medtronic, Inc., Merck Serono, Minster Pharmaceuticals plc, Neuralieve Inc., the NIH/NINDS, NuPathe Inc., Pfizer Inc, St. Jude Medical, and Valeant Pharmaceuticals International; serves on the editorial boards of Cephalalgia and Current Pain and Headache Reports ; serves on the speakers' bureaus for Endo Pharmaceuticals, GlaxoSmithKline, and Merck Serono; serves as a consultant for Amgen, Novartis, Opti-Nose, and Sepracor Inc.; receives publishing royalties for Wolff's Headache, 8 th edition (Oxford University Press, 2009) and Handbook of Headache (Cambridge University Press, 2010); his employer receives research support from AGA, Allergan, Boston Scientific, CAPNIA, Coherex, Endo, GlaxoSmithKline, Lilly, MAP, Medtronic, Merck, the NIH/NINDS, NuPathe, St. Jude Medical, Valeant, and Zogenix, Inc.; and receives research support from the American Headache Society and the International Headache Society. Dr. Dodick serves on scientific advisory boards and as a consultant for Allergan, Inc., Pfizer Inc., Novartis, Merck Serono, NuPath Inc., Nautilus, Coherex Medical, Boston Scientific, Medtronic, Inc., GlaxoSmithKline, CoLucid Pharmaceuticals, Autonomic Technologies, Eli Lilly and Company, Miller Medical, Neuralieve Inc., NeurAxon, Inc., St. Jude Medical, Inc., Zogenix, Inc., CogniMed Inc., MAP Pharmaceuticals, Inc., Lundbeck Inc., IMPAX Laboratories, Inc., and the NIH/NINDS; has received funding for travel or speaker honoraria from CogniMed Inc., Miller Medical, and Annenberg Center for Health Sciences; serves as Editor-in-Chief of Cephalalgia , Editor-in-Chief and on the editorial boards of The Neurologist, Lancet Neurology , and Postgraduate Medicine ; and has served as Editor-in-Chief of Headache Currents and as an Associate Editor of Headache ; receives publishing royalties for Wolff's Headache, 8th edition (Oxford University Press, 2009) and Handbook of Headache (Cambridge University Press, 2010); and receives research support from Boston Scientific, Medtronic, Inc., Advanced Neurostimulation Systems, St. Jude Medical, Inc., and the NIH/NINDS. Dr. Lindblad receives salary from and is part owner of The EMMES Corporation, a Coordinating Center for clinical trials. Dr. Holroyd has served as a consultant for Endo Pharmaceuticals and Takeda Pharmaceutical Company Limited and received research support from Endo Pharmaceuticals and the NIH. M. Harrington receives salary from The EMMES Corporation, a Coordinating Center for clinical trials. Dr. Mathew has served on scientific advisory boards for Allergan, Inc., GlaxoSmithKline, and Nautilus; has served on speakers' bureaus for and received speaker honoraria from GlaxoSmithKline, Nautilus, Allergan, Inc.; and has received research support from Merck Serono, AstraZeneca, Pfizer Inc, and Endo Pharmaceuticals. Dr. Hirtz reports no disclosures.",
year = "2012",
month = mar,
day = "27",
doi = "10.1212/WNL.0b013e31824d5846",
language = "English (US)",
volume = "78",
pages = "976--984",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "13",
}