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. 2025 Feb;15(1):e200359.
doi: 10.1212/CPJ.0000000000200359. Epub 2024 Oct 8.

Characterizing Prodrome (Premonitory Phase) in Migraine: Results From the PRODROME Trial Screening Period

Todd J Schwedt  1 , Richard B Lipton  1 , Peter J Goadsby  1 , Chia-Chun Chiang  1 , Brad C Klein  1 , Cory Hussar  1 , Chengcheng Liu  1 , Sung Yun Yu  1 , Michelle Finnegan  1 , Joel M Trugman  1
Affiliations

Characterizing Prodrome (Premonitory Phase) in Migraine: Results From the PRODROME Trial Screening Period

Todd J Schwedt et al. Neurol Clin Pract. 2025 Feb.

Abstract

Background and objective: Limited data are available describing the frequency, severity, and consistency of prodromal symptoms followed by headache. This analysis of the PRODROME trial screening period characterized prodromal symptoms in people with migraine, including the most common symptoms and their severity, and the frequency and consistency with which prodromal symptoms were followed by headache.

Methods: PRODROME was a multicenter, randomized, double-blind, placebo-controlled, crossover trial conducted in the United States that enrolled adults with 2-8 migraine attacks per month who stated they could identify prodromal symptoms that were reliably followed by a headache. The trial included a 60-day screening period designed to test the predictive validity of "qualifying prodrome events" before the onset of headache. Participants used an eDiary to report qualifying prodrome events, defined as prodromal symptoms whereby the participant was confident a headache would follow within 1-6 hours. This analysis evaluated common prodromal symptoms and their severity, time from prodrome onset to headache onset, and the percentage of participants who identified prodromal symptoms that were followed by a headache ≥75% of the time over the 60-day screening period.

Results: A total of 920 participants entered eDiary data, with a mean of 5.2 qualifying prodrome events during the 60-day screening period. A total of 4,802 qualifying prodrome events were recorded. The most common prodromal symptoms identified were sensitivity to light (57.2%; 2,748/4,802), fatigue (50.1%; 2,408/4,802), neck pain (41.9%; 2,013/4,802), sensitivity to sound (33.9%; 1,630/4,802), either difficulty thinking or concentrating (30.0%; 1,442/4,802), and dizziness (27.8%; 1,333/4,802). Of all qualifying prodrome events reported, 81.5% (3,913/4,802) were followed by headache of any intensity within 1-6 hours. For each participant, a mean of 84.4% of their qualifying prodrome events were followed by a headache within 1-6 hours, with 76.9% of participants identifying qualifying prodrome events that were followed by headache within 1-6 hours ≥75% of the time.

Discussion: Participants were able to identify migraine attacks in which prodromal symptoms were reliably followed by a headache within 1-6 hours. These findings suggest the potential for initiating treatment during the prodrome to prevent headache.

Trial registration information: ClinicalTrials.gov NCT04492020. Submitted: July 27, 2020; First patient enrolled: August 21, 2020. clinicaltrials.gov/study/NCT04492020.

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Conflict of interest statement

T.J. Schwedt reports that he serves on the Board of Directors for the American Headache Society. Within the prior 12 months, he has received research support from American Heart Association, Henry Jackson Foundation, Mayo Clinic, National Headache Foundation, NIH, Patient-Centered Outcomes Research Institute, Pfizer, SPARK Neuro, and US Department of Defense. Within the past 12 months, he has received personal compensation for serving as a consultant or advisory board member for AbbVie, Allergan, Eli Lilly, Linpharma, Lundbeck, Satsuma, Scilex, and Theranica. He holds stock options in Aural Analytics and Nocira. He has received royalties from UpToDate. R.B. Lipton reports support for the present study from AbbVie, research support paid to his institution from the NIH, the S&L Marx Foundation, the Czap Foundation, the National Headache Foundation, and the US Food and Drug Administration, and personal fees from AbbVie/Allergan, American Academy of Neurology, American Headache Society, Amgen, Biohaven, Biovision, Boston, Dr. Reddy's (Promius), electroCore, Eli Lilly, GlaxoSmithKline, Grifols, Lundbeck (Alder), Merck, Pernix, Pfizer, Teva, Vector, and Vedanta Research. He holds stock/options in Axon, Biohaven, CoolTech and Manistee. P.J. Goadsby reports support for the present study and personal fees during the conduct of the study from AbbVie; a grant from Celgene; personal fees from Aeon Biopharma, Amgen, CoolTech LLC, Dr Reddy's, Eli Lilly, Epalex, Impel Neuropharma, Lundbeck, Novartis, Praxis, Sanofi, Satsuma, Shiratronics, Teva Pharmaceuticals, and Tremeau; personal fees for advice through Gerson Lehrman Group, Guidepoint, SAI Med Partners, and Vector Metric; fees for educational materials from CME Outfitters and WebMD; fees for publishing from Massachusetts Medical Society and Oxford University Press; and fees for medicolegal advice in headache. He has a patent for Magnetic stimulation for headache, which is licensed to eNeura without fee. C.-C. Chiang has received research support from the American Heart Association with funds paid to her institution. She has received personal compensation for serving as a consultant for Satsuma and eNeura. B.C. Klein has received personal compensation for serving as a consultant for AbbVie, Currax, Eli Lilly and Company, and Ipsen; for serving on a speakers bureau for AbbVie, Amgen, Biohaven, Eli Lilly and Company, Impel, Lundbeck, Teva, and Theranica; and for serving as a Shareholder with AppsByDocs, LLC; and has received research support from AbbVie and Eli Lilly and Company and has a noncompensated relationship as a Chair, Practice Management Committee with the American Headache Society that is relevant to American Academy of Neurology interests or activities. C. Liu and J.M. Trugman are employees of AbbVie and may hold AbbVie stock. S.Y. Yu and M. Finnegan were employees of AbbVie at time of the study and may hold AbbVie stock. C. Hussar is an employee of OPEN Health Scientific Communications. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.

Figures

Figure 1
Figure 1. Kaplan-Meier Plot of Time to Onset of a Headache of Any Intensity for All Prodrome Events in the Screening Period
Figure 2
Figure 2. Kaplan-Meier Plot of Time to Onset of a Headache of Moderate to Severe Intensity for All Prodrome Events in the Screening Period
See this image and copyright information in PMC

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