- Kenneth A Holroyd, distinguished professor12,
- Constance K Cottrell, assistant research professor12,
- Francis J O’Donnell, clinical assistant professor234,
- Gary E Cordingley, associate professor4,
- Jana B Drew, assistant research professor12,
- Bruce W Carlson, associate professor1,
- Lina Himawan, biostatistician1
- 1Ohio University, Athens, OH 45701, USA
- 2Headache Treatment and Research, Westerville, OH 43081, USA
- 3OrthoNeuro Inc, Westerville, OH 43081
- 4Ohio University College of Osteopathic Medicine, Athens, OH 45701
- Correspondence to: K A Holroyd, 225 Porter Hall, Athens, OH 45701, USA
- Accepted 29 June 2010
Objective To determine if the addition of preventive drug treatment (β blocker), brief behavioural migraine management, or their combination improves the outcome of optimised acute treatment in the management of frequent migraine.
Design Randomised placebo controlled trial over 16 months from July 2001 to November 2005.
Setting Two outpatient sites in Ohio, USA.
Participants 232 adults (mean age 38 years; 79% female) with diagnosis of migraine with or without aura according to International Headache Society classification of headache disorders criteria, who recorded at least three migraines with disability per 30 days (mean 5.5 migraines/30 days), during an optimised run-in of acute treatment.
Interventions Addition of one of four preventive treatments to optimised acute treatment: β blocker (n=53), matched placebo (n=55), behavioural migraine management plus placebo (n=55), or behavioural migraine management plus β blocker (n=69).
Main outcome measure The primary outcome was change in migraines/30 days; secondary outcomes included change in migraine days/30 days and change in migraine specific quality of life scores.
Results Mixed model analysis showed statistically significant (P≤0.05) differences in outcomes among the four added treatments for both the primary outcome (migraines/30 days) and the two secondary outcomes (change in migraine days/30 days and change in migraine specific quality of life scores). The addition of combined β blocker and behavioural migraine management (−3.3 migraines/30 days, 95% confidence interval −3.2 to −3.5), but not the addition of β blocker alone (−2.1 migraines/30 days, −1.9 to −2.2) or behavioural migraine management alone (−2.2 migraines migraines/30 days, −2.0 to −2.4), improved outcomes compared with optimised acute treatment alone (−2.1 migraines/30 days, −1.9 to −2.2). For a clinically significant (≥50% reduction) in migraines/30 days, the number needed to treat for optimised acute treatment plus combined β blocker and behavioural migraine management was 3.1 compared with optimised acute treatment alone, 2.6 compared with optimised acute treatment plus β blocker, and 3.1 compared with optimised acute treatment plus behavioural migraine management. Results were consistent for the two secondary outcomes, and at both month 10 (the primary endpoint) and month 16.
Conclusion The addition of combined β blocker plus behavioural migraine management, but not the addition of β blocker alone or behavioural migraine management alone, improved outcomes of optimised acute treatment. Combined β blocker treatment and behavioural migraine management may improve outcomes in the treatment of frequent migraine.
Trial registration Clinical trials NCT00910689.
We thank the following people for their assistance in carrying out the trial: Carol Nogrady, Kimberly Hill, Suzanne Smith, Bernadette Devantes Heckman, Brenda Pinkerman, Gregg Tkachuk, Sharon Waller, Donna Shiels, Kathleen Darchuk, Yi Chen, Timur Skeini, Manish Singla, Swati Dalmai, and Lori Arnott.
Contributors: KAH, CKC, FJO’D, and GEC were responsible for the study concept and design. KAH, BWC, and FJO’D obtained funding. KAH, CKC, FJO’D, GEC, and JBD were involved in acquisition of data. KAH, BWC, and LH analysed and interpreted the data. LH, BWC, and KAH did the statistical analysis. Victor Heh assisted with data analysis. Jenifer Labus did the computerised randomisation. KAH drafted the manuscript, and all authors critically revised it for important intellectual content. KAH, CKC, FJO’D, and JBD provided administrative, technical, or material support. KAH, CKC, and JBD supervised the study. KAH is the guarantor.
Funding: Grant R01-NS-32374 (awarded to KAH) from the National Institutes of Health provided primary support for this trial. Merck Pharmaceuticals and GlaxoSmithKline Pharmaceuticals donated triptans for the trial, which was their only involvement. These organisations had no role in the data collection, statistical analysis, or writing of this article or the decision to submit for publication.
Competing interests: KAH has consulted for ENDO Pharmaceuticals and for Takeda Pharmaceuticals North America and received an investigator initiated grant from ENDO Pharmaceuticals. He has also received support from the National Institutes of Health (NINDS; NS32375). CKC has received research funding and materials from GlaxoSmithKline Pharmaceuticals (GSK) and Merck and participates in industry sponsored research involving GSK, Merck, UCB Pharma, and Allergan. FJO’D has received research funding and materials from GSK and Merck; receives educational funding from GSK, Merck, and Allergan; participates in industry sponsored research involving GSK, Merck, UCB Pharma, and Allergan; and has consulted for and received honorariums from GSK. GEC owns stock in Johnson and Johnson, Novartis, and Wyeth Pharmaceuticals.
Ethical approval: All participants provided written informed consent according to procedures approved by the Ohio University Human Subjects Committee.
Data sharing: Technical appendix with statistical code and details of analyses available from the corresponding author at () or biostatistician ( ). Consent was not obtained from participants, but risk of identification is low.
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