Demographic variables, headache features, comorbidity, and treatment factors may predict inadequate response to acute migraine treatment at two hours and at 24 hours, according to research published in the November issue of Headache. Similar factors may predict which patients with an adequate response at two hours will have an inadequate response at 24 hours.

The data suggest substantial unmet acute treatment needs at the population level, said Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at the Albert Einstein College of Medicine in Bronx, New York, and colleagues. “A good response at two hours was associated with doing well at 24 hours. This [result] highlights the importance of initial response to treatment in overall patient outcomes.”

An Analysis of AMPP Data

Much of the literature intended to identify predictors of response to migraine treatment focuses on outcomes of individual attacks. Study populations generally are limited, furthermore, to the select group of patients willing to participate in trials. A thorough evaluation of unmet acute treatment needs requires a more representative sample population, as well as information about long-term responses to multiple attacks, said Dr. Lipton.

He and his colleagues examined data from the American Migraine Prevalence and Prevention (AMPP) Study to identify factors that predict the success or failure of acute treatment at two hours and at 24 hours. The investigators focused on the 2006 AMPP survey, which included the Migraine Treatment Optimization Questionnaire (mTOQ). Eligible participants met criteria for episodic migraine, used acute pharmacologic treatment for migraine, and provided the necessary data for the researchers’ analysis.

In all, 14,520 people responded to the 2006 survey, 10,006 of whom met International Classification of Headache Disorders-3 beta criteria for migraine. Dr. Lipton’s group examined two questions from the mTOQ to assess pain-response outcomes following acute treatment. The first question asked whether the respondent was pain-free within two hours of treatment for most attacks. The second asked whether one dose of medication usually relieved the respondent’s headache and kept it away for at least 24 hours.

In all, 8,233 people responded to both questions. Patients who responded “never,” “rarely,” or “less than half the time” to the first or second question were considered to have an inadequate two-hour pain-free response or an inadequate 24-hour pain relief response, respectively. A response of “half the time or more” was defined as an adequate response. In addition, the researchers defined a 24-hour sustained pain-free response as an adequate response to both questions. Participants with an adequate two-hour response and an inadequate 24-hour response were considered to have recurrence. To identify outcome predictors, Dr. Lipton and colleagues conducted logistic regression analyses.

Most Participants Had Inadequate Response

Most participants (56.0%) reported inadequate two-hour pain-free response to usual acute treatment, and 53.6% of respondents reported inadequate 24-hour pain relief. Of the 44.0% of people with adequate two-hour pain-free response, 74.3% reported sustained pain relief at 24 hours.

The significant predictors of inadequate two-hour pain-free response were greater pain intensity, cutaneous allodynia, depression, higher BMI, and higher average monthly headache day frequency. Factors that protected against an inadequate two-hour pain-free response included using a preventive medication for migraine, female gender, and being married.

Factors that predicted inadequate 24-hour pain relief included greater feelings of depression, cutaneous allodynia, greater monthly headache day frequency, greater headache pain intensity, overuse of acute medication, lack of health insurance, being a smoker, and being unmarried. Predictors of inadequate 24-hour sustained pain-free response were greater monthly headache day frequency, cutaneous allodynia, meeting criteria for depression, acute medication overuse, and migraine symptom severity.

A Need for Treatment Optimization

Previous studies have found an association between high BMI and severe and progressive forms of migraine. This association “may reflect a proinflammatory state in obesity that renders treatment less effective,” said Dr. Lipton.

The authors’ finding of an association between depression and inadequate response is consistent with previous research suggesting that depression is a risk factor for headache progression. Preventive migraine medications were protective against this outcome, however.

A possible explanation for smokers’ higher likelihood of having inadequate 24-hour pain relief is that “smoking may alter drug metabolism and shorten the duration of action of selected acute treatments,” said Dr. Lipton. In addition, the association between monthly headache days and inadequate 24-hour pain relief “may reflect the fact that more frequent attacks may be associated with prolonged activation of neuronal networks involved in pain processing during attacks, which may lead to lowering the threshold for subsequent attacks.”

One limitation of the current study is its reliance on self-reported data, said the authors. The questionnaire that the researchers used is limited by recall bias, recency effects, and the risk that the preceding month did not represent the individual’s usual experience. Nonetheless, mTOQ items have demonstrated high reliability and validity. Other study limitations include the retrospective design, the high proportion of participants who used more than one acute treatment, and the fact that the data are 10 years old.

On the other hand, the study examined a large, representative sample of the US population. It also included various validated measures to diagnose migraine and to assess headache-related disability, allodynia, and depression.

“These results show that unmet needs remain, and the expansion of therapeutic options for episodic migraine is needed, as well as optimizing treatment by carefully designing comprehensive treatment plans with existing acute therapies with various doses, routes of administration, preventive and interventional treatment approaches, behavioral therapies, neuromodulators, and other empirically validated approaches to achieve optimized treatment,” Dr. Lipton concluded.

—Erik Greb

Suggested Reading

Lipton RB, Munjal S, Buse DC, et al. Predicting inadequate response to acute migraine medication: results from the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2016;56(10):1635-1648.

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