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By Dara G. Jamieson, MD
Clinical Associate Professor of Neurology, Weill Cornell Medical College
Dr. Jamieson reports that she is a consultant for AbbVie.
SYNOPSIS: Patients with migraine who have an insufficient response to acute treatment medications, including triptans, risk developing medication overuse headache (MOH). The most successful treatment for MOH is withdrawal of the offending acute pain medications combined with early use of a migraine preventative medication.
SOURCES: Lombard L, Ye W, Nichols R, et al. A real-world analysis of patient characteristics, treatment patterns, and level of impairment in patients with migraine who are insufficient responders vs responders to acute treatment. Headache 2020; June 8. doi: 10.1111/head.13835. [Online ahead of print].
Carlsen LN, Munksgaard SB, Nielsen M, et al. Comparison of 3 treatment strategies for medication overuse headache: A randomized clinical trial. JAMA Neurol 2020; May 26. doi: 10.1001/jamaneurol.2020.1179. [Online ahead of print].
Inadequate response to acute migraine medication is exceedingly common in patients with migraine and it has a major deleterious effect on the quality of life of migraine patients. Lombard et al investigated differences between patients with migraine who did and did not respond sufficiently to acute treatment to identify characteristics associated with insufficient response to medication. The researchers used the Adelphi Migraine Disease-Specific Program (AMDSP), a real-world, point-in-time, cross-sectional survey of primary care physicians, neurologists, and their patients, to acquire data between January and March 2014 from 583 patients with migraine.
Using logistic regression, investigators analyzed the data to determine the association between patient factors and insufficient response. Migraine medication responders (383/583 [65.7%]) were defined as patients with migraine who achieved pain freedom within two hours of acute treatment in ≥ 4 of 5 attacks, while insufficient migraine responders (200/583 [34.3%]) achieved pain freedom in ≤ 3 of 5 attacks. As compared to responders, a larger proportion of insufficient responders had four or more migraine headache days/month, had ever been prescribed three or more unique preventive treatment regimens, and had delayed taking acute medication for a migraine attack. Insufficient responders were statistically more likely to have comorbid depression and other psychological conditions. Chronic migraine and medication overuse headache (MOH), as well as increased use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and over-the-counter (OTC) medications, were statistically more common in migraine patients with insufficient response to acute migraine medications. Another recent publication from the same group, using data from the 2017 AMDSP, concluded that triptan insufficient responders had worse health-related quality of life and work productivity.1 As higher users of OTC medications, triptan insufficient responders were at increased risk of MOH. MOH is defined by the International Classification of Headache Disorders, third edition, criteria as, “Headache occurring on 15 or more days/month in a patient with a pre-existing primary headache and developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more or 15 or more days/month, depending on the medication) for more than three months. It usually, but not invariably, resolves after the overuse is stopped.”2 A vulnerable headache patient taking excessively frequent acute pain medication, especially opioids and combination analgesics, may develop MOH, a disabling condition that can be refractory to treatment.
At the Danish Headache Center, Carlsen et al conducted an open-label, randomized clinical trial from October 2016 to June 2019 using 120 outpatients with MOH who were taking simple analgesics, combined analgesics, and triptans. Three treatment arms were randomly assigned in a 1:1:1 allocation: withdrawal plus preventive treatment, preventive treatment without withdrawal, or withdrawal with optional preventive treatment started two months after withdrawal. One hundred two patients, with a mean age of 44 years, and 81 women, completed the six-month follow-up. In the withdrawal plus preventive medication group, 58% of patients had completely discontinued acute pain medications, with 56% who discontinued in the withdrawal alone group. The remaining patients in the withdrawal and withdrawal plus preventive treatment groups no longer overused medications, with a decrease of acute pain medication use to a range of one to nine days per month. All strategies were effective, without treatment differences, in the primary outcome of change in headache days per month at six months, with a reduction of 12.3 days with withdrawal plus prevention, 9.9 days with prevention alone, and 8.5 days with withdrawal alone. No treatment difference was found in the secondary outcomes of reduction of migraine days per month, use of short-term medication, or headache intensity. Improvement of MOH to episodic migraine was statistically more likely in the withdrawal plus preventive group (74%) than in the preventative group (60%) or in the withdrawal group (42%). Cure of MOH occurred in 97% of patients in the withdrawal plus preventive group, compared with 89% in the withdrawal group and 74% in the preventive alone group. There was a 30% (relative risk, 1.3; 95% confidence interval, 1.1-1.6) increased chance of MOH cure in the withdrawal plus preventive group compared with the preventive group (P = 0.03). While all three treatment strategies decreased migraine days, the withdrawal of frequent use of acute pain medication, in combination with the early onset use of a preventive medication, achieved the best results.
Since there is no cure that can obliterate migraine, people with migraines need to find the most effective preventive and symptomatic treatments, including lifestyle modification and medications. The lack of an effective treatment that can abort the pain at its onset has a significant impact on the quality of life and productivity of patients with migraine and risks development of MOH, which is common and often unrecognized. MOH is precipitated when large quantities of acute pain medications are used to treat primary and secondary headaches. Neurologists have an obligation to remind patients with frequent headaches that they are at risk of developing MOH, and neurologists must resist entreaties for large amounts of triptans or for highly habituating medications, such as opioids or combination medications containing butalbital.
If chronification of headache develops as the result of excessive use of acute pain medication, then a withdrawal schedule, generally with tapering, should be implemented in combination with the early use of a daily preventive medication. If the offending acute pain medication is not withdrawn, headache reduction is not likely to be achieved. Treatment of chronic headaches, including migraine, is complicated. The advice to take an acute pain medication early, at the onset of pain, may paradoxically contribute to an increased frequency of use of that medication, even though early treatment is symptomatically more effective. This paradox, that early use works better but may increase the risk of medication overuse, emphasizes the need for acute abortive medication that reliably gives relief, all the time, every time.
Financial Disclosure: Neurology Alert’s Editor in Chief Matthew Fink, MD; Peer Reviewer M. Flint Beal, MD; Editorial Group Manager Leslie Coplin;
Editor Jason Schneider; Executive Editor Shelly Morrow Mark; and Accreditations Director Amy M. Johnson, MSN, RN, CPN, report no financial
relationships relevant to this field of study.