What was the research about?
Chronic migraine is when people have headaches 15 or more days per month, with migraines for at least 8 of those days. Patients can take medicines, such as non-steroidal anti-inflammatory medicines and triptans, to relieve symptoms. But about half of people with chronic migraine use these medicines more often than recommended because of the pain and disability the headaches cause. When these medicines are taken too often for more than three months, it’s called medication overuse. Medication overuse can lead to more frequent headaches, migraine attacks, and other serious side effects.
In this study, the research team compared two approaches to treat adult patients with chronic migraine and medication overuse. In both, patients took a medicine to prevent migraines. Then patients either:
- Stopped taking the overused medicine and switched to a different type of medicine up to two days per week to relieve symptoms, or
- Continued taking the overused medicine on as many days as needed to relieve symptoms.
What were the results?
After 12 weeks, the two approaches worked about the same to reduce the number of days with a migraine. Patients who stopped taking the overused medicine had about 9.3 migraine days per month compared with 9.1 days for patients who continued it. The research team’s statistical analysis showed that staying on the overused medicine wasn’t worse for controlling symptoms than switching medicines.
But patients who stopped the overused medicine took medicine to treat symptoms less often than patients who continued it. They were also less likely to overuse migraine medicines.
The two approaches didn’t differ in:
- Patients' quality of life
- Whether migraines made it hard to do daily tasks or caused disability
- Adverse events, such as high blood pressure, fatigue, or stomach pain
- Whether patients remained in the study
Who was in the study?
The study included 720 adult patients with chronic migraine and medication overuse. Of these, 75 percent were White, 6 percent were Black, and 1 percent were Asian; 13 percent were Hispanic. The average age was 44, and 87 percent were women. Patients received care at one of 34 headache, neurology, or primary care clinics across the United States.
What did the research team do?
The research team assigned patients by chance to one of the two treatment approaches. They surveyed patients at the start of the study and again 9–12 weeks later.
Patients kept a diary for weeks 1–12 and other 4-week periods over one year. They recorded how often they had headaches, how intense they were, and how long they lasted. Patients also recorded whether they used medicine to treat symptoms.
Patients and headache specialists helped plan and conduct the study.
What were the limits of the study?
The study didn’t look at how different types of medicines prevent migraines or relieve symptoms.
Future research could compare how different types of medicines improve migraines and medication overuse.
How can people use the results?
Patients and their doctors can use the results when treating chronic migraine and medication overuse.
To compare the effectiveness of two treatment approaches in reducing the number of headache days among patients with chronic migraine and medication overuse
|Design||Randomized controlled trial|
|Population||720 adult patients at least 21 years of age who had chronic migraine with medication overuse; patients averaged 12.8 moderate to severe headache days per 28 days prior to randomization.|
Primary: number of moderate to severe headache days
Secondary: proportion of participants in a medication overuse pattern during weeks 9–12; frequency of days with headache-related disability; frequency of days taking symptomatic medications; headache frequency; participant dropout rates; quality of life; disability; frequency of moderate to severe headache days during weeks 21–24 and 45–48; adverse events
|Timeframe||Up to 12-week follow-up for primary outcome|
This randomized, pragmatic non-inferiority trial compared two approaches to reducing headache frequency for patients with chronic migraine and medication overuse. Medication overuse occurs when people with chronic migraine use medications to relieve symptoms, such as butalbital-containing medications, triptans, or non-steroidal anti-inflammatory medications, too often. Medication overuse can lead to high-frequency headaches, functional impairment, and the potential for medication-related toxicity and side effects.
Researchers randomly assigned patients to one of two groups. In both groups, patients received a prescription for a preventive medication, such as amitriptyline, propranolol, or topiramate. In the first group, patients discontinued their overused medication and switched to an alternative migraine medication in a different class. Patients used the alternative medication two days or fewer per week. In the second group, patients continued taking the overused medication and had no limit on how often they could use it.
The study included 720 adult patients with chronic migraine and medication overuse. Of these, 75% were White, 6% were Black, and 1% were Asian; 13% were Hispanic. The average age was 44, and 87% were female. Patients received care at one of 34 headache specialty, general neurology, or primary care clinics across the United States.
To assess study outcomes, patients completed surveys at baseline and 12 weeks. They kept a diary for weeks 1–12 and other 4-week periods over one year to record the frequency, duration, and intensity of headaches and whether they used medication to treat symptoms.
Patients and headache specialists helped plan and conduct the study.
During weeks 9–12, the two treatment approaches did not differ significantly in the average number of days with moderate to severe headaches, meeting criteria for demonstrating non-inferiority for continuing the overused medication versus switching for patients receiving preventive medication. Patients who switched from the overused medication averaged 9.3 of 28 days, while patients who continued the overused medication averaged 9.1 days. The frequency of moderate to severe headache days during weeks 1–2 also did not differ between the two approaches.
Compared with patients who continued to take the overused medication, patients who switched to a different medication had fewer days on which they used medication to treat symptoms (p<0.001) and were less likely to be in a medication overuse pattern during weeks 9–12 (p<0.001).
The two groups did not differ significantly on other secondary outcomes.
The study did not differentiate effects by the class of preventive or symptomatic medication.
Conclusions and Relevance
In this study, continuing to take the overused medication was not inferior to switching to another medication in reducing the number of days with moderate to severe headaches for patients receiving a preventive medication. However, switching to another medication may help patients reduce medication overuse.
Future Research Needs
Future research could examine whether treatment approaches differ by type of preventive medication or class of overused medication.
Final Research Report
View this project's final research report.
More to Explore...
Neurology Podcast (April 4, 2022): Patient-Centered Treatment of Migraine with Medication Overuse
In this episode, Principal Investigator Todd J. Schwedt, MD, MS, discusses the treatment of chronic migraine with medication overuse through the patient-centered MOTS clinical trial.
Article Highlight: Many people with chronic migraines use medication more often than recommended. This overuse can have the undesired effect of more migraines and headaches and other serious side effects. The MOTS (Medication Overuse Treatment Strategy) Trial compared two ways to treat adult patients who have chronic migraine and medication overuse. It found that not switching or limiting medication wasn’t worse than switching medication, according to results published in Neurology. But the study also found that patients who stopped the overused medicine took it to treat symptoms less often than patients who continued it. They were also less likely to overuse migraine medicines.
Read an accompanying editorial in Neurology.
Results of This Project
Related Journal Citations
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers were laudatory in their reviews of this report, stating that the study was well-designed and the report well-written.
- One reviewer asked how much the COVID-19 pandemic affected study recruitment and participant attrition. The researchers acknowledged that the pandemic limited in-person research and clinical visits. With approval from the study sites and stakeholders, the researchers changed the protocol to allow for telehealth study visits in place of in-person visits.
- The reviewer also questioned whether the mostly White makeup of the study participants was related to barriers to care for non-White patients to access adequate migraine care. The researchers acknowledged that there have been significant barriers to receiving adequate migraine care for people from the underrepresented racial and ethnic groups and added this study limitation to their report discussion.
Conflict of Interest Disclosures
Study Registration Information
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