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Original Investigation
May 26, 2020

Comparison of 3 Treatment Strategies for Medication Overuse Headache: A Randomized Clinical Trial

Author Affiliations
  • 1Currently a PhD student at the University of Copenhagen, Copenhagen, Denmark
  • 2Danish Headache Center, Rigshospitalet, Glostrup, Denmark
JAMA Neurol. 2020;77(9):1069-1078. doi:10.1001/jamaneurol.2020.1179
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.


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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