Withdrawal Plus Preventive Treatment Superior to Treat Medication Overuse Headache


The first study to attempt to directly compare 3 debated treatment strategies to treat medication overuse headache showed the most significant change in monthly headache days by using withdrawal plus preventive treatment.

Data from a clinical trial comparing 3 different treatment strategies for medication overuse headache (MOH) suggests that withdrawal therapy combined with preventive medication from the start of withdrawal should be recommended as primary care treatment.

The study randomly assigned participants 1:1:1 to 3 outpatient treatments consisting of withdrawal plus preventive treatment (n = 31), preventive treatment without withdrawal (n = 35), or withdrawal with optional preventive treatment 2 months after withdrawal (n = 36).

The investigators noted that all 3 strategies were effective in their respective ways, after 6 months headache days per month were reduced by 12.3 (95% CI, 9.3—15.3) in the withdrawal plus preventive group, compared to 9.9 (95% CI, 7.2–12.6) in the preventive-only group, and by 8.5 (95% CI, 5.6–11.5) in the withdrawal group (P = .20 for all).

The research was conducted by Louise N. Carlsen, MD, PhD student, University of Copenhagen, Denmark, and colleagues, and they suggested that reduction of migraine days per month, use of short-term medication, or headache intensity were all similar among all 3 treatment strategies. “Nevertheless, the numerically largest reductions in headache days,migraine days, days with short-term medication use, and headache pain intensity were seen in the withdrawal plus preventive group,” they noted.

Migraine days per month were reduced by 5.0 (95% CI, 1.4—8.6) in the withdrawal plus preventive group, 4.1 (95% CI, 1.1–7.1) in the preventive group, and 3.3 (95% CI, 0.9–5.7) in the withdrawal group (P = .74). Additionally, pain intensity scores were reduced by 28.1 (95% CI, 21.1—35.1), 23.7 (95% CI, 17.1–30.2), and 20.8 (95% CI, 12.2–29.4) in the 3 groups, respectively.

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In total, 23 of 31 patients (74.2%) in the withdrawal plus preventive group reverted to episodic headache, compared with 21 of 35 (60%) in the preventive group and 15 of 36 (41.7%) in the withdrawal group, which was significant (P = .03).

Additionally, fully cured MOH occurred in 30 of 31 patients (96.8%) in the withdrawal plus preventive group, compared with 26 of 35 (74.3%) in the preventive group and 32 of 36 (88.9%) in the withdrawal group (P = .03). Carlsen and colleagues documented that those findings led 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).

The study contained 120 patients, 102 (mean age, 43.9 [standard deviation (SD), 11.8] years; 81 women [79.4%]) who completed a 6-month follow-up in the tertiary sector at the Danish Headache Center from October 25, 2016, to June 28, 2019. Data were analyzed from July 3 to September 6, 2019.

Patients were evaluated on headache days per month after 6 months as a primary outcome, and change in monthly migraine days, use of short-term medication, pain intensity, number of responders, patients with remission to episodic headache, and cure MOH all as predefined secondary outcomes. Other prespecified secondary outcomes included number of patients with at least 50% reduction in headache days per month at 2 months and number of patients with medication overuse at 2 and 6 months.

Patients who were admitted to the withdrawal plus preventive group and preventive group received information about the specific preventive treatment that was chosen according to the Danish Headache Center existing guidelines.

“Patients with previous MOH due to frequent headache need effective medication to prevent development of a new chronic headache and relapse of MOH,” Carlson and colleagues also concluded. “Arguments for postponing the start of preventive treatment could be uncertain headache diagnosis during medication overuse, prior use of ineffective preventive treatment, and fear of adverse effects of ineffective preventive treatments.”


Carlsen LN, Munksgaard SB, Nielsen M, et al. Comparison of 3 treatment strategies for medication overuse headache. JAMA Neurol. Published online May 26, 2020. doi: 10.1001/jamaneurol.2020.1179.

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