Low Percentage of Migraine Episodes Associated With Stress

Vives‐Mestres, PhD

Study results published in Headache suggests that a low percentage of patients with migraine had a majority of their attacks associated with increased levels of perceived stress, and that perceived stress peaked during the pain phase of the migraine cycle._¹

After assessing data from 351 individuals and 2115 migraine episodes, lead author Marina Vives‐Mestres, PhD, and colleagues observed that only 7.1% (n = 25) of patients had a majority of their attacks associated with increased levels of perceived stress. Stress was rated on a 0‐10 scale once per day at a chosen time with a single question, “How stressed have you felt today?” Participants used the digital health platform N1‐Headache for 90 days of daily data entry regarding migraine, headache symptoms, and lifestyle factors.

"Clearly, average population results can only be applied to a minority of individuals; providing a compelling rationale for generating individual phenotypic profiles before administration of individual treatment plans," said Vives-Mestres, who is an analytics lead at Curelator (the developer of N1-Headache) and visiting professor of statistics at Universitat de Girona, in a statement.²

When conducting cluster analysis of the data from the N1 Headache digital platform, the group observed 3 common patterns of variation in perceived stress levels across the cycle of migraine:

• Cluster 1: “Let down” pattern. Consisted of perceived stress in P_i, then fell in the P_pre, and then further decreased in P₀ relative to P_i.
• Cluster 2: “Flat” pattern. Consisted of perceived stress which was relatively unchanged throughout the migraine cycle.
• Cluster 3: “Stress as a trigger/symptom” pattern. Consisted of perceived stress in P_pre with increased relative to P_i, and then further increased in P₀ relative to P_i.

Cluster 1 contained 16.7% (n = 354) of the 2115 total episodes, while Cluster 2 and Cluster 3 consisted of 59.2% (n = 1253) and 24.0% (n = 508), respectively. In total, 3.4% (n = 12) of participants had more than 50% of their episodes fall into Cluster 1, while 61.5% (n = 216) and 7.1% (n = 25) had more than 50% of their episodes fall into clusters 2 and 3, respectively.

There were 40 participants with more than 90% of their episodes in cluster 2, but no participants reached this mark in clusters 1 or 3.

Vives-Mestres and colleagues concluded that identifying how patterns of perceived stress vary across the migraine cycle may contribute insights into disease biology, triggers, and protective factors, and provide a framework for targeting individualized treatment plans.

"The N of 1 methodology used in this study applies the approach of personalized medicine to help individuals understand their headache patterns," said Richard Lipton, MD, Edwin S. Lowe Professor, vice-chair of neurology, and director, Montefiore Headache Center, Albert Einstein College of Medicine, in a statement. "There is tremendous variation from person to person in their trigger factors. The typical approach of assessing population averages generates results that are difficult for individuals to apply. If red wine triggers your headaches but not mine, there is no need for me to avoid it."

The majority of those in the study, 61.5% (n = 216), had flat stress levels leading to more than 50% of their migraine attacks. A small percentage, 3.4% (n = 12), had half of their attacks following decreasing levels of stress. The remaining portion of individuals, 28%, had a variable mixture of increasing, flat and/or decreasing levels of stress preceding their attacks.

Vives-Mestres et al categorized days into phases of the migraine cycle: pre‐migraine headache, defined as the 2 days prior to the first day with migraine headache (P_pre); migraine headache days (P₀); post‐migraine headache, defined as the 2 days following the last migraine day (P_post); and interictal days (P_i). migraine episodes were included only as occurrences with days in all 4 phases with at least 1 reported daily perceived stress value in each phase.

Of the 351 total patients, 2.3% (n = 8) reported having chronic migraine (≥15 headache days per month). Eighty‐six percent of the sample (n = 302) were female, and the mean number of migraine days per month was 6.1 (standard deviation [SD], 2.3; range, 2‐13) with a mean number of episodes of 6.0 (SD, 1.0; range, 5‐10) over the 90‐day study period.

"These findings strongly suggest that, for the vast majority of patients, the role of perceived stress in triggering migraine attacks is less important than previously hypothesized," Serena Orr, MD, senior author of the study, headache specialist, pediatric neurologist, and researcher, Cumming School of Medicine, University of Calgary, said in a statement. "This contradicts the previous belief that increases in stress consistently trigger migraine attacks because we found that this relationship is rather uncommon."

REFERENCES
1. Vives-Mestres M, Casanova A, Buse DC, et al. Patterns of Perceived Stress Throughout the Migraine Cycle: A Longitudinal Cohort Study Using Daily Prospective Diary Data. Headache. 2021. 61(1):90-102. doi: 10.1111/head.13943.
2. New Study by the University of Calgary and Curelator Reveals Surprising Lack of Association Between Stress and Migraine. News release. January 25, 2020. Accessed February 4, 2021. https://www.prnewswire.co.uk/news-releases/new-study-by-the-university-of-calgary-and-curelator-reveals-surprising-lack-of-association-between-stress-and-migraine-880806324.html