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Onset of Stress Offers a Reliable Warning of Ensuing Episodic Migraine

A patient’s perception of stress was used to build a model supporting the reliability of predicting future migraines.

With Timothy T. Houle, PhD, and Brian M. Grosberg, MD

Suspected headache triggers are not very well understood for either their causality or associations with headaches.1 However, there is evidence that early timing of migraine treatment is important to treatment efficacy, such as treatment with triptans while pain is mild as opposed to more advanced.2

Progress in developing tools that prompt patients to anticipate migraine attacks points to the role of stress as a useful predictive factor was presented in a study,3 led by Timothy T. Houle, PhD, associate professor of the anesthesiology, critical care, and pain medicine at Massachusetts General Hospital in Boston, Massachusetts, and colleagues, and published in Headache: The Journal of Head and Face Pain.

Episodic migraines often follow periods of stressStress may be predictive of migraine onset.

“Perceived triggers are often avoided by people with headaches in an attempt to reduce the chances of experiencing a headache,” said Dr. Houle.

Management Value in Anticipating Migraine Triggers  

“Identifying the initiating factors that reliably predict headache onset in migraine is of great potential importance for several reasons,” said Brian M. Grosberg, MD, director of the Hartford Healthcare Headache Center, and professor of neurology at the University of Connecticut School of Medicine, to Practical Pain Management.

"First, when headache onset is predictable, migraine sufferers may learn to take precautionary measures during times of increased vulnerability to attacks. Second, knowledge of the factors associated with headache onset might provide insights into the mechanisms of attack initiation. Finally, the ability to successfully predict attacks clinically may lead to an expansion of the paradigm of preemptive treatment (ie, beginning treatment before exposure to the trigger and continuing it through the period of expected headache susceptibility),” he said. 

Noting the uncertainty around many suspected triggers, Dr. Houle said, “we are excited about finding a trigger that can actually be used to assist people who suffer from migraines in understanding their risk levels.”3

Studying Relationship of Stress as Migraine Trigger

“Simply knowing that stress is related to headaches, as is widely believed, does not allow an individual who is suffering from migraine to track their stress levels or to estimate their actual risk in the near future. Our research offers a first step in allowing individuals who suffer from migraine to track their migraine risk over the near term,”3 Dr. Houle told Practical Pain Management.

The goal of the study was to construct a model for predicting migraine attacks based on input from the migraine sufferer, with this study evaluating stress as an input.3 Since many treatments for migraines involve taking an abortive after a migraine has begun, the researchers focused on this modeling approach with the hope that patients with migraines may be better able to mitigate precipitants or their effects.

One premise built into the study related to the process in which headaches may be more likely to occur with subsidence of stress, during what the authors termed a “let-down” period.3 “The mechanisms for this association are not clear, but it appears that experiencing higher than normal levels of stress places a sufferer at greater risk for headache when the stress subsides,” said Dr. Houle.

Methodology for Stress and Episodic Migraine Study

Participants— who had episodic migraines that occurred more than twice per month and totaling 4 to 14 days of the month—made twice-daily electronic diary entries during a span from September 2009 to May 2014.3 These entries addressed headache activity, characteristics (such as intensity on a scale of 0-10), and treatment, as well as stress levels.

Stresses were assessed with the Daily Stress Inventory,4 a 58-item tool addressing stressors from the previous 24 hours, with impacts scored on a severity scale from 1-7. Initially, participants completed diaries using Pendragon forms software on a Palm Pilot, followed by an iPod Touch, and later participants used forms from the web employing REDCap software from their personal devices.3

A total of 95 participants (86 female and 9 male) logged 4626 days of electronic diary entries, with headaches occurring on 38.5% of 4195 days included in the overall analysis. Frequency and intensity of stressors both fit well with forecast models, with the best-fitting model emphasizing averaged stress intensity and showing an area-under-the-curve value of 0.73 (95% CI, 0.71-0.75; P < 0.001). Validation of this model by the leave-one-out method gave an AUC of 0.65 (95% CI, 0.6-0.67; P < 0.0001).3

Migraines May Follow Periods of Stress

Forecast models showed good reliability between actual and predicted headache probabilities, but a resolution of predictions was not as strong.3 The researchers noted that other predictors or analyses of more days leading up to a headache attack may be useful for increasing the sharpness of the predictions. Even so, the research team had hypothesized that just an awareness of stress may be used to forecast headache risk, and this hypothesis was supported by the study’s results.3

“Before we can use the model clinically, we need to validate it on additional samples of people who might have different headache patterns with exposure to stress. All prediction models were associated with uncertainty and we need to better understand the degree of uncertainty in these predictions when applied to the general population of people. Hopefully, the model will be useful in the clinical setting (ie, treatment providers may utilize it with their patients) in the not-to-distant future,” Dr. Houle said.

“This study by Houle and colleagues2 represents a significant first step in applying a forecasting model as a means to formally predict the onset of a migraine attack in individuals with an episodic migraine in relation to stress,” Dr. Grosberg, MD, concluded in speaking with Practical Pain Management.

Drs. Houle, Turner, Golding, Tegeler, and Porter report no conflicts. Dr. Martin is on the speaker’s bureau for Allergan and Duramed, is a speaker/consultant to Avenir, and a consultant for Eli Lilly and Amgen, Dr. Penzien reports an unrestricted grant from Merck.

Last updated on: January 30, 2018
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