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Comparison of 3 Treatment Strategies for Medication Overuse HeadacheA Randomized Clinical Trial

Educational Objective
To determine the most effective treatment for medication overuse headache.
Key Points

Question  Which treatment is the most effective for medication overuse headache?

Findings  This randomized clinical trial of 120 patients with medication overuse headache compared treatments consisting of withdrawal and preventive medication, preventive medication, and withdrawal alone. Withdrawal and preventive medication achieved the best results with a mean reduction of 12.3 headache days per month.

Meaning  Given these findings, the use of withdrawal and preventive medication from the start of withdrawal is recommended for treatment of medication overuse headache.

Abstract

Importance  Medication overuse headache (MOH) is a disabling, globally prevalent disorder representing a well-known and debated clinical problem. Evidence for the most effective treatment strategy is needed.

Objective  To compare 3 treatment strategies for MOH.

Design, Setting, and Participants  This open-label, randomized clinical trial with 6 months of follow-up was conducted in the tertiary sector at the Danish Headache Center, Glostrup, from October 25, 2016, to June 28, 2019. Of 483 patients with MOH referred during the inclusion period, 195 met the criteria consisting of migraine and/or tension-type headache, 18 years or older, eligibility for outpatient treatment, no severe physical or psychiatric disorder, no other addiction, and not pregnant or breastfeeding. Of these, 75 refused participation and 120 were included. Data were analyzed from July 3 to September 6, 2019.

Interventions  Random assignment (1:1:1 allocation) to 1 of the 3 outpatient treatments consisting of (1) withdrawal plus preventive treatment, (2) preventive treatment without withdrawal, or (3) withdrawal with optional preventive treatment 2 months after withdrawal.

Main Outcomes and Measures  The primary outcome was change in headache days per month after 6 months. Predefined secondary outcomes were change in monthly migraine days, use of short-term medication, pain intensity, number of responders, patients with remission to episodic headache, and cured MOH.

Results  Of 120 patients, 102 (mean [SD] age, 43.9 [11.8] years; 81 women [79.4%]) completed the 6-month follow-up. Headache days per month were reduced by 12.3 (95% CI, 9.3-15.3) in the withdrawal plus preventive group, by 9.9 (95% CI, 7.2-12.6) in the preventive group, and by 8.5 (95% CI, 5.6-11.5) in the withdrawal group (P = .20). No difference was found in reduction of migraine days per month, use of short-term medication, or headache intensity. In the withdrawal plus preventive group, 23 of 31 patients (74.2%) reverted to episodic headache, compared with 21 of 35 (60.0%) in the preventive group and 15 of 36 (41.7%) in the withdrawal group (P = .03). Moreover, 30 of 31 patients (96.8%) in the withdrawal plus preventive group were cured of MOH, compared with 26 of 35 (74.3%) in the preventive group and 32 of 36 (88.9%) in the withdrawal group (P = .03). These findings corresponded to a 30% (relative risk, 1.3; 95% CI, 1.1-1.6) increased chance of MOH cure in the withdrawal plus preventive group compared with the preventive group (P = .03).

Conclusion and Relevance  All 3 treatment strategies were effective, but based on these findings, withdrawal therapy combined with preventive medication from the start of withdrawal is recommended as treatment for MOH.

Trial Registration  ClinicalTrials.gov Identifier: NCT02993289

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Article Information

Accepted for Publication: February 28, 2020.

Corresponding Author: Rigmor Højland Jensen, MD, DMSc, Danish Headache Center, Rigshospitalet, Valdemar Hansens Vej 5, 1A, 2600 Glostrup, Denmark (rigmor.jensen@regionh.dk).

Published Online: May 26, 2020. doi:10.1001/jamaneurol.2020.1179

Author Contributions: Ms Carlsen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Carlsen, Munksgaard, Westergaard, Bendtsen, Jensen.

Acquisition, analysis, or interpretation of data: Carlsen, Munksgaard, Nielsen, Engelstoft, Bendtsen, Jensen.

Drafting of the manuscript: Carlsen, Bendtsen, Jensen.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Carlsen.

Obtained funding: Jensen.

Administrative, technical, or material support: Carlsen, Nielsen, Engelstoft, Jensen.

Supervision: Munksgaard, Westergaard, Bendtsen, Jensen.

Conflict of Interest Disclosures: Ms Carlsen reported receiving grants from TrygFonden during the conduct of the study and giving a lecture for Allergan plc outside the submitted work. Dr Munksgaard reported receiving nonfinancial support from TEVA Pharmaceutical Industries and Novartis International AG outside the submitted work and previously receiving travel grants from Merck Sharpe & Dohme, Allergan plc, and Pfizer, Inc, and giving lectures for TEVA Pharmaceutical Industries, Berlin-Chemie AG, and UCB. Dr Nielsen reported receiving grants from Danish Medical Society Copenhagen during the conduct of the study. Dr Jensen reported receiving grants from TrygFonden during the conduct of the study; grants from Lundbeck Foundation and NovoNordisk Foundation outside the submitted work; conducting clinical trials for Eli Lilly and Company, ATI, and electroCore, Inc; giving lectures for ATI, TEVA Pharmaceutical Industries, Novartis International AG, Allergan plc, and electroCore, Inc; serving as a director in Lifting The Burden and the Danish Headache Center; and serving as past president of the European Headache Federation and as prior trustee in the International Headache Society. No other disclosures were reported.

Additional Contributions: We thank project nurses Mette Bisgaard, BA, Annette Vangaa Rasmussen, BA, Annette Fjeldborg Jonasson, BA, Malene Danø Rasmussen, BA, and Hjørdis Rasmussen, BA, at the Danish Headache Center, who contributed considerably to the data collection; to the Biomedical Department, University of Copenhagen, for statistical support; and the Tryg Foundation for funding the salary of Ms Carlsen. The named contributors received no additional compensation for this work.

Data Sharing Statement: See Supplement 3.

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