Is there a causal relationship between stress and migraine? Current evidence and implications for management

BACKGROUND: The purpose of this narrative review is to examine the literature investigating a causal relationship between stress and migraine and evaluate its implications for managing migraine. METHODS: PubMed, PsycINFO and CINAHL were searched from 1988 to August 2021, identifying 2223 records evaluating the relationship between stress and migraine. Records were systematically screened. All potentially relevant records were thematically categorized into six mechanistic groups. Within each group the most recent reports providing new insights were cited. RESULTS: First, studies have demonstrated an association of uncertain causality between high stress loads from stressful life events, daily hassles or other sources, and the incidence of new-onset migraine. Second, major stressful life events seem to precede the transformation from episodic to chronic migraine. Third, there is some evidence for changes in levels of stress as a risk factor for migraine attacks. Research also suggests there may be a reversed causality or that stress-trigger patterns are too individually heterogeneous for any generalized causality. Fourth, migraine symptom burden seems to increase in a setting of stress, partially driven by psychiatric comorbidity. Fifth, stress may induce sensitization and altered cortical excitability, partially explaining attack triggering, development of chronic migraine, and increased symptom burden including interictal symptom burden such as allodynia, photophobia or anxiety. Finally, behavioral interventions and forecasting models including stress variables seem to be useful in managing migraine. CONCLUSION: The exact causal relationships in which stress causes incidence, chronification, migraine attacks, or increased burden of migraine remains unclear. Several individuals benefit from stress-oriented therapies, and such therapies should be offered as an adjuvant to conventional treatment and to those with a preference. Further understanding the relationship between stress, migraine and effective therapeutic options is likely to be improved by characterizing individual patterns of stress and migraine, and may in turn improve therapeutics.