Persistent frequent nausea is associated with progression to chronic migraine: AMPP study results

Michael L. Reed, Kristina M. Fanning, Daniel Serrano, Dawn C. Buse, Richard B. Lipton

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Background Though nausea is a cardinal feature of migraine, its influence on migraine progression has not been evaluated. This article aims to evaluate persistent frequent headache-related nausea (PFN) in persons with episodic migraine (EM) as a predictor of new onset chronic migraine (CM). Methods This prospective cohort study uses data from the 2007 and 2008 American Migraine Prevalence and Prevention study surveys to identify subgroups with episodic International Classification of Headache Disorders, 2nd edition defined migraine and either PFN or no or low frequency nausea (NLFN). PFN was defined by the presence of nausea ≥ half the time in both 2007 and 2008. NLFN was defined by nausea that was present < half the time, rarely or never in both years. Persons were considered CM in 2009 if they met symptom criteria for migraine with headaches ≥15 days per month over the preceding 3 months. Univariate differences in demographics for PFN and NLFN were evaluated with chi-square. Binary logistic regressions were performed hierarchically to assess progression to CM in 2009 as a function of nausea status in 2007 and 2008. The initial model included sociodemographic variables only. Subsequent models added the following variables in a hierarchical manner: migraine symptom severity composite score (to control for the impact of other headache features), headache-related disability, depression, opioid use, and an interaction term for nausea status and opioid use. Odds ratios (OR) and 95% confidence intervals (CI) contrasted PFN and NLFN on the rate of progression to CM in 2009. Results There were 3182 respondents with headache symptom and frequency data available for all 3 years of the analysis. PFN was found in 43.7% (1389) of respondents, and 3.4% (47) progressed to CM. NLFN was seen in 27.6% (877) of the EM group, and 1.5% progressed to CM. In comparison with the NLFN group, PFN was more common in females (P < .001) and Caucasians (P < .06). PFN was associated with a doubling of the risk of progression to CM after adjusting for sociodemographic variables (OR 2.09, 95% CI 1.11-3.91, P = .022). Adding the symptom composite score and headache-related disability covariates to the model attenuated the association slightly (OR 2.00, 95% CI 1.03-3.87, P = .04). With the addition of depression, the association fell just below statistical significance but progression risk with PFN remained at nearly two-fold that of the NLFN group (OR 1.90, 95% CI 0.98-3.71, P = .059). When opioid use and the nausea by opioid use interaction are added to the final model, the significant effect and the doubling of CM progression risk for those with PFN was retained (OR 2.24, 95% CI 1.07-4.70, P = .033). Conclusions Persistent frequent nausea is common (43.7%) among persons with episodic migraine. After controlling for sociodemographics, migraine symptom severity, headache-related disability, depression, and opioid medication use, migraineurs with frequent nausea that persisted for 2 years of study were twice as likely to progress to CM compared to those with no or low frequency nausea. The study is limited by self-reports of symptom and headache frequency data and the use of modified diagnostic criteria. Additional prospective research is needed to confirm study findings. Persistent frequent nausea could be a marker for the risk of progression to CM or it could be in the causal pathway.

Original languageEnglish (US)
Pages (from-to)76-87
Number of pages12
Issue number1
StatePublished - Jan 1 2015


  • chronic migraine
  • impact
  • migraine
  • nausea
  • progression
  • severity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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