Patterns of Perceived Stress Throughout the Migraine Cycle: A Longitudinal Cohort Study Using Daily Prospective Diary Data

Objectives: To describe patterns of perceived stress across stages of the migraine cycle, within and between individuals and migraine episodes as defined for this study. Methods: Individuals with migraine aged ≥18 years, who were registered to use the digital health platform N1-Headache^TM, and completed 90 days of daily data entry regarding migraine, headache symptoms, and lifestyle factors were eligible for inclusion. Perceived stress was rated once a day at the participant’s chosen time with a single question, “How stressed have you felt today?” with response options graded on a 0-10 scale. Days were categorized into phases of the migraine cycle: P_pre = pre-migraine headache (the 2 days prior to the first day with migraine headache), P₀ = migraine headache days, P_post = post-migraine headache (the 2 days following the last migraine day with migraine headache), and P_i = interictal days (all other days). Episodes, defined as discrete occurrences of migraine with days in all 4 phases, were eligible if there was at least 1 reported daily perceived stress value in each phase. Individuals with ≥5 valid episodes, and ≥75% compliance (tracking 90 days in 120 calendar days or less) were eligible for inclusion in the analysis. Results: Data from 351 participants and 2115 episodes were included in this analysis. Eighty-six percent of the sample (302/351) were female. The mean number of migraine days per month was 6.1 (range 2-13, standard deviation = 2.3) and the mean number of episodes was 6.0 (range 5-10, standard deviation = 1.0) over the 90-day period. Only 8 (8/351, 2.3%) participants had chronic migraine (defined as 15 or more headache days per month with at least 8 days meeting criteria for migraine). Cluster analysis revealed 3 common patterns of perceived stress variation across the migraine cycle. For cluster 1, the “let down” pattern, perceived stress in the interictal phase (P_i) falls in the pre-headache phase (P_pre) and then decreases more in the migraine phase (P₀) relative to P_i. For cluster 2, the “flat” pattern, perceived stress is relatively unchanging throughout the migraine cycle. For cluster 3, the “stress as a trigger/symptom” pattern, perceived stress in P_pre increases relative to P_i, and increases further in P₀ relative to P_i. Episodes were distributed across clusters as follows: cluster 1: 354/2115, 16.7%; cluster 2: 1253/2115, 59.2%, and cluster 3: 508/2115, 24.0%. Twelve participants (12/351, 3.4%) had more than 50% of their episodes fall into cluster 1, 216 participants (216/351, 61.5%) had more than 50% of their episodes fall into cluster 2, and 25 participants (25/351, 7.1%) had more than 50% of their episodes fall into cluster 3. There were 40 participants with ≥90% of their episodes in cluster 2, with no participants having ≥90% of their episodes in cluster 1 or 3. Conclusions: On an aggregate level, perceived stress peaks during the pain phase of the migraine cycle. However, on an individual and episode basis, there are 3 dominant patterns of perceived stress variation across the migraine cycle. Elucidating 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.