Treatment of Medication Overuse Headache: Effect and Predictors After 1 Year

A Randomized Controlled Trial

Louise N. Carlsen MD, PhD; Carolien Rouw MD; Maria L. Westergaard MD, PhD; Mia Nielsen MD; Signe B. Munksgaard MD, PhD; Lars Bendtsen MD, PhD, Dr.Med.Sci.; Rigmor H. Jensen MD, Dr.Med.Sci.


Headache. 2021;61(7):1112-1122. 

In This Article

Abstract and Introduction


Background: Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a longer follow-up period are lacking.

Objective: (1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year.

Methods: Patients with MOH and migraine and/or tension-type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year.

Results: Of 120 patients, 96 completed 1-year follow-up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4–25.8) to 15.0 (13.0–17.0) (p < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7–13.9) in the W+P group, 10.8 days (95% CI: 7.6–14) in the P+pW group, and 7.9 days (95% CI: 5.1–10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09–1.31), more days with acute medication (aOR 1.11; 1.03–1.19), higher pain intensity (aOR 1.04; 1.01–1.08), and depression (aOR 4.7; 1.38–18.95), whereas higher self-rated health (aOR 0.61; 0.36–0.97) and high caffeine consumption (aOR 0.40; 0.16–0.96) were predictors of a lower risk of chronic headache. No adverse events were reported.

Conclusions: All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients.


Medication overuse headache (MOH) is a chronic secondary headache caused by medication overuse.[1] The condition is a common clinical problem that should be managed in an effective manner because these patients are highly impaired.[2,3] However, the best treatment strategy for MOH has been debated for years.[4,5] Questions have been raised about when and how preventive medication should be initiated and how the overused medication should be withdrawn. Recently, we addressed some of these questions in an open-label, randomized, controlled study comparing three treatment strategies for MOH: withdrawal and immediate preventive medication, preventive medication without withdrawal, and withdrawal therapy with delayed optional preventive medication after 2 months. We concluded that a combination of abrupt withdrawal and early preventive medication should be the recommended treatment strategy.[6,7]

Our first study had a 6-month follow-up period. In previous studies, between 13% and 41% of patients relapse within the first year after the start of the treatment for MOH.[8] It is, therefore, of utmost importance to follow these patients over a longer period. The purpose of this paper was, therefore, to report the effect of treatment of patients with MOH followed for a whole year after the start of treatment, measured in various parameters, and to compare the three treatment strategies: (a) withdrawal with immediate preventive treatment (W+P), (b) preventive treatment with potential withdrawal after 6 months (P+pW), and (c) withdrawal with optional preventive treatment after 2 months (W+pP) (Figure 1). Furthermore, we aimed to identify clinical predictors of still having chronic headache after 1 year. Our hypothesis was that the treatment strategy including withdrawal with immediate preventive treatment would have the largest treatment effect, including reduction in monthly headache days and days with acute medication.

Figure 1.

Study design [Color figure can be viewed at]