Journal article
Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine
The New England journal of medicine, Vol.376(2), pp.115-124
01/12/2017
DOI: 10.1056/nejmoa1610384
PMCID: PMC5226887
PMID: 27788026
Abstract
Which medication, if any, to use to prevent the headache of pediatric migraine has not been established.
We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment.
A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt.
There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281 ).
Details
- Title: Subtitle
- Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine
- Creators
- Scott W Powers - From the Department of Pediatrics, University of Cincinnati College of Medicine (S.W.P., A.D.H.), and the Division of Behavioral Medicine and Clinical Psychology (S.W.P., L.A.C.), the Office for Clinical and Translational Research (L.L.K.), and the Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center - all in Cincinnati; the Department of Biostatistics, Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City (C.S.C., D.J.E., E.A.K., J.W.Y.); and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (L.L.P.)Christopher S Coffey - From the Department of Pediatrics, University of Cincinnati College of Medicine (S.W.P., A.D.H.), and the Division of Behavioral Medicine and Clinical Psychology (S.W.P., L.A.C.), the Office for Clinical and Translational Research (L.L.K.), and the Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center - all in Cincinnati; the Department of Biostatistics, Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City (C.S.C., D.J.E., E.A.K., J.W.Y.); and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (L.L.P.)Leigh A Chamberlin - From the Department of Pediatrics, University of Cincinnati College of Medicine (S.W.P., A.D.H.), and the Division of Behavioral Medicine and Clinical Psychology (S.W.P., L.A.C.), the Office for Clinical and Translational Research (L.L.K.), and the Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center - all in Cincinnati; the Department of Biostatistics, Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City (C.S.C., D.J.E., E.A.K., J.W.Y.); and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (L.L.P.)Dixie J Ecklund - From the Department of Pediatrics, University of Cincinnati College of Medicine (S.W.P., A.D.H.), and the Division of Behavioral Medicine and Clinical Psychology (S.W.P., L.A.C.), the Office for Clinical and Translational Research (L.L.K.), and the Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center - all in Cincinnati; the Department of Biostatistics, Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City (C.S.C., D.J.E., E.A.K., J.W.Y.); and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (L.L.P.)Elizabeth A Klingner - From the Department of Pediatrics, University of Cincinnati College of Medicine (S.W.P., A.D.H.), and the Division of Behavioral Medicine and Clinical Psychology (S.W.P., L.A.C.), the Office for Clinical and Translational Research (L.L.K.), and the Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center - all in Cincinnati; the Department of Biostatistics, Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City (C.S.C., D.J.E., E.A.K., J.W.Y.); and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (L.L.P.)Jon W Yankey - From the Department of Pediatrics, University of Cincinnati College of Medicine (S.W.P., A.D.H.), and the Division of Behavioral Medicine and Clinical Psychology (S.W.P., L.A.C.), the Office for Clinical and Translational Research (L.L.K.), and the Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center - all in Cincinnati; the Department of Biostatistics, Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City (C.S.C., D.J.E., E.A.K., J.W.Y.); and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (L.L.P.)Leslie L Korbee - From the Department of Pediatrics, University of Cincinnati College of Medicine (S.W.P., A.D.H.), and the Division of Behavioral Medicine and Clinical Psychology (S.W.P., L.A.C.), the Office for Clinical and Translational Research (L.L.K.), and the Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center - all in Cincinnati; the Department of Biostatistics, Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City (C.S.C., D.J.E., E.A.K., J.W.Y.); and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (L.L.P.)Linda L Porter - From the Department of Pediatrics, University of Cincinnati College of Medicine (S.W.P., A.D.H.), and the Division of Behavioral Medicine and Clinical Psychology (S.W.P., L.A.C.), the Office for Clinical and Translational Research (L.L.K.), and the Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center - all in Cincinnati; the Department of Biostatistics, Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City (C.S.C., D.J.E., E.A.K., J.W.Y.); and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (L.L.P.)Andrew D Hershey - From the Department of Pediatrics, University of Cincinnati College of Medicine (S.W.P., A.D.H.), and the Division of Behavioral Medicine and Clinical Psychology (S.W.P., L.A.C.), the Office for Clinical and Translational Research (L.L.K.), and the Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center - all in Cincinnati; the Department of Biostatistics, Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City (C.S.C., D.J.E., E.A.K., J.W.Y.); and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (L.L.P.)CHAMP Investigators
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.376(2), pp.115-124
- Publisher
- United States
- DOI
- 10.1056/nejmoa1610384
- PMID
- 27788026
- PMCID
- PMC5226887
- ISSN
- 1533-4406
- eISSN
- 1533-4406
- Grant note
- U01 NS077108 / NINDS NIH HHS K24 DK059973 / NIDDK NIH HHS U01 NS076788 / NINDS NIH HHS
- Language
- English
- Date published
- 01/12/2017
- Academic Unit
- Biostatistics
- Record Identifier
- 9983997312102771
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