Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial

Kenneth A Holroyd, Constance K Cottrell, Francis J O'Donnell, Gary E Cordingley, Jana B Drew, Bruce W Carlson, Lina Himawan, Kenneth A Holroyd, Constance K Cottrell, Francis J O'Donnell, Gary E Cordingley, Jana B Drew, Bruce W Carlson, Lina Himawan

Abstract

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.

Conflict of interest statement

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.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787849/bin/holk727131.f1_default.jpg
Fig 1 Flow of participants in trial. *Reported that other time demands prevented completion of trial tasks (such as completing study appointments). †Side effects attributed to triptan (T) or β blocker (B). ‡Discontinued from trial for protocol violation (for example, failed to take preventive drug). §Decided to become or became pregnant
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787849/bin/holk727131.f2_default.jpg
Fig 2 Mean change in number of migraines per 30 days from run-in of optimised acute treatment estimated for each of four treatments. Vertical lines at months 10 and 16 indicate primary end point and longer term assessment point
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787849/bin/holk727131.f3_default.jpg
Fig 3 Mean change in number of migraine days per 30 days from run-in of optimised acute treatment estimated for each of four treatments. Vertical lines at months 10 and 16 indicate primary end point and longer term assessment point
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787849/bin/holk727131.f4_default.jpg
Fig 4 Mean change in migraine specific quality of life scores from run-in of optimised acute treatment estimated for each of four treatments. Vertical lines at months 10 and 16 indicate primary end point and longer term assessment point

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