Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

Headache. 2020 Feb;60(2):416-429. doi: 10.1111/head.13708. Epub 2019 Dec 14.


Objectives: The objectives of this study were to determine the rates of nausea, phonophobia, and photophobia reported overall and as the most bothersome symptom (MBS) in individuals with migraine and to identify individual characteristics associated with each of the 3 candidate MBSs.

Background: The MBS has emerged as an important coprimary efficacy endpoint in clinical trials of acute treatments for migraine, as recommended by the Food and Drug Administration. The current understanding of how persons with migraine designate an associated symptom as the most bothersome has been assessed primarily in the context of randomized trials.

Methods: Respondents (n = 95,821) in the cross-sectional, observational Migraine in America Symptoms and Treatment (MAST) study were adults (aged ≥18 years) recruited from a US nationwide online research panel. A validated diagnostic screener identified 15,133 individuals who met modified International Classification of Headache Disorders (ICHD)-3 beta criteria for migraine and reported at least 1 monthly headache day (MHD) over the previous 3 months. The survey ascertained sociodemographic variables, headache-related disability, MHDs, cutaneous allodynia, medication overuse, a migraine symptom severity score, pain interference, noncephalic pain, anxiety and depression symptoms, visual aura over the previous year, and acute treatment optimization. The current analysis is based on respondents who also completed a 6-month follow-up assessment that included questions about their most bothersome headache symptom.

Results: A total of 7518 respondents completed the 6-month follow-up, and 6045 met inclusion criteria and were included in the analysis. The mean age of respondents was 47 (SD 13.4) years, 76.0% (4596/6045) were women, and 84.8% (5103/6017) were white. Among all respondents, 64.9% reported all 3 migraine symptoms. The MBS was photophobia in 49.1% (2967/6045), nausea in 28.1% (1697/6045), and phonophobia in 22.8% (1381/6045). Respondents reporting photophobia as the MBS were more likely to be men, to be obese, and to report visual aura. Those reporting nausea as the MBS were more likely to be women, to have lower incomes, and to report lower levels of treatment optimization. Respondents reporting phonophobia as the MBS were more likely to have cutaneous allodynia and less likely to have visual aura.

Conclusion: Most people with migraine in the MAST observational study reported all 3 cardinal symptoms of nausea, photophobia, and phonophobia. As in clinical trials, the most common MBS was photophobia. Patient profiles differed among the groups defined by their MBS.

Keywords: coprimary endpoints; epidemiology; migraine; most bothersome symptom.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cross-Sectional Studies
  • Diagnostic Self Evaluation*
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperacusis* / diagnosis
  • Hyperacusis* / epidemiology
  • Hyperacusis* / etiology
  • Male
  • Middle Aged
  • Migraine Disorders* / complications
  • Migraine Disorders* / diagnosis
  • Migraine Disorders* / epidemiology
  • Nausea* / diagnosis
  • Nausea* / epidemiology
  • Nausea* / etiology
  • Photophobia* / diagnosis
  • Photophobia* / epidemiology
  • Photophobia* / etiology
  • Severity of Illness Index*
  • Sex Factors
  • Socioeconomic Factors
  • United States / epidemiology
  • Young Adult