Patient-Centered Treatment of Chronic Migraine With Medication Overuse

Abstract

Background and ObjectivesOveruse of symptomatic (i.e., acute) medications is common among those with chronic migraine. It is associated with developing frequent headaches, medication side effects, and reduced quality of life. The optimal treatment strategy for patients who have chronic migraine with medication overuse (CMMO) has long been debated. The study objective was to determine whether migraine preventive therapy without switching or limiting the frequency of the overused medication was noninferior to migraine preventive therapy with switching from the overused medication to an alternative medication that could be used on ≤2 d/wk.MethodsThe Medication Overuse Treatment Strategy (MOTS) trial was an open-label, pragmatic clinical trial, randomizing adult participants 1:1 to migraine preventive medication and (1) switching from the overused medication to an alternative used ≤2 d/wk or (2) continuation of the overused medication with no maximum limit. Participants were enrolled between February 2017 and December 2020 from 34 clinics in the United States, including headache specialty, general neurology, and primary care clinics. The primary outcome was moderate to severe headache day frequency during weeks 9 to 12 and subsequently during weeks 1 to 2 after randomization.ResultsSeven hundred twenty participants were randomized; average age was 44 (SD 13) years; and 87.5% were female. At baseline, participants averaged 22.5 (SD 5.1) headache days over 4 weeks, including 12.8 (SD 6.7) moderate to severe headache days and 21.4 (SD 5.8) days of symptomatic medication use. Migraine preventive medication without switching of the overused medication was not inferior to preventive medication with switching for moderate to severe headache day frequency during weeks 9 to 12 (switching 9.3 [SD 7.2] vs no switching 9.1 [SD 6.8]; p = 0.75, 95% CI −1.0 to 1.3). The treatment strategies also provided similar outcomes during the first 2 weeks (switching 6.6 [SD 3.7] moderate to severe headaches days vs no switching 6.4 [SD 3.6]; p = 0.57, 95% CI −0.4 to 0.7).DiscussionWhen reduction in moderate to severe headache days was used as the outcome of interest for the management of CMMO, migraine preventive medication without switching or limiting symptomatic medication is not inferior to migraine preventive medication with switching to a different symptomatic medication with a maximum limit of 2 treatment days per week.Trial Registration InformationClinicalTrials.gov identifier NCT02764320.Classification of EvidenceThis study provides Class III evidence that, for patients who have CMMO, migraine preventive medication without switching or limiting the overused medication is noninferior to migraine preventive medication with switching and limiting symptomatic medication.

Classification and Diagnosis of Primary Headache Disorders

“…29 Studies of treatment strategies in MOH have begun to shed more light on these complex issues. 30 One of the most notable observations about MOH is that it seems to be primarily a condition seen in migraine and possibly TTHA. Therefore, if medication overuse is a causal factor in migraine "chronification," we might consider the condition a subset of the primary headache disorder-say "CM with medication overuse.…”

Treatment of chronic migraine with medication overuse: A perspective

“…The MOTS trial was a large, multicenter, open-label, pragmatic, randomized clinical trial that compared two treatment strategies for patients with CM with MO. 3 A total of 720 patients, enrolled within primary care, general neurology, and headache specialty clinics across the United States, were randomized 1:1 to (1) preventive medication with immediate switching from the overused as-needed medication to an as-needed medication from another class that could be taken up to 2 days per week (i.e., the "switching" strategy) or (2) preventive medication without switching and with no instructions given for limiting the as-needed medication (i.e., the "no switching" strategy). The primary outcome was the frequency of moderate-tosevere headache days during weeks 9-12 (non-inferiority analysis) and weeks 1-2 post-randomization (superiority analysis; conducted only if non-inferiority was demonstrated for weeks 9-12).…”

Refractory Headaches

“…38 Whether the best treatment approach is switching the overused medication to a less frequently used alternative or keeping it without restrictions while optimizing preventive treatment may depend on the situation. 4 For example, it may be better to switch for people with a high frequency of medication overuse and it may be better to not limit baseline acute medication use for people with higher anxiety at baseline while working on preventive treatment optimization, but more data are needed. 4 Most patients who abruptly discontinue a frequently used acute treatment experience worsening in their headaches, and possibly autonomic disturbances, anxiety, and sleep disturbances, for approximately 2 to 7 days.…”

“…4 For example, it may be better to switch for people with a high frequency of medication overuse and it may be better to not limit baseline acute medication use for people with higher anxiety at baseline while working on preventive treatment optimization, but more data are needed. 4 Most patients who abruptly discontinue a frequently used acute treatment experience worsening in their headaches, and possibly autonomic disturbances, anxiety, and sleep disturbances, for approximately 2 to 7 days. 39 Prednisone does not seem to help with withdrawal symptoms.…”

“…The topic of refractory headaches is important because they are associated with disability, the need for more persistent medical management, and empathic patient support as refractory headaches have a psychological impact. 1 2 3 4…”