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Am Fam Physician. 2021;103(7):439-440

Clinical Question

What are the effective approaches to managing patients with medication overuse headaches?

Bottom Line

In this study, achieving cure from medication overuse headaches after six months was likely regardless of strategy: detoxification (discontinuation of analgesic) plus pharmacologic prophylaxis, pharmacologic prophylaxis without withdrawal, or detoxification with pharmacologic preventive therapy delayed for two months. Although the authors favor the combined strategy, it seems like this is a good time for shared decision-making. (Level of Evidence = 2b−)


This study was fundamentally aimed at determining if detoxification is needed in patients with medication overuse headaches by comparing three outpatient strategies: detoxification plus pharmacologic prophylaxis, pharmacologic prophylaxis without withdrawal, and detoxification with pharmacologic preventive therapy delayed for two months. The pharmacologic prophylactic therapy was at the discretion of the treating physician, and monoclonal antibody therapy was not available. The following prophylactic agents were ultimately used: metoprolol, lisinopril, candesartan (Atacand), topiramate (Topamax), amitriptyline, mirtazapine (Remeron), and onabotulinumtoxinA (Botox). All patients had access to rescue antiemetic therapy during withdrawal. Forty patients with medication overuse headaches were randomized to receive each strategy (N = 120); after six months, between 10% and 22.5% dropped out of each arm (overall drop-out rate was 15%). More than a 20% drop-out rate is worrisome. Although the presentation of their data is confusing, the authors report that medication overuse headaches were cured in 97% of those completing the detoxification plus pharmacologic prophylaxis strategy compared with 74% of those completing the pharmacologic preventive strategy and 89% of those completing the detoxification strategy. They also observed no significant differences in the number of headache days, in the subsequent use of short-term analgesics, or in headache severity. Each strategy appeared to be highly effective, but the unmasked design, loose medication management, and spotty drop-out rates raise some concerns about the data. The authors plan additional follow-up at 12 months and at four years.

Study design: Randomized controlled trial (nonblinded)

Funding source: Unknown/not stated

Allocation: Concealed

Setting: Outpatient (specialty)

Reference: Carlsen LN, Munksgaard SB, Nielsen M, et al. Comparison of 3 treatment strategies for medication overuse headache: a randomized clinical trial. JAMA Neurol. 2020;77(9): 1069–1078.

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