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Open research questions in Migraine and Headache Studies

208 unresolved questions extracted from the limitations and future-work sections of 745 Migraine and Headache Studies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The study identifies the challenge of limited direct evidence for some treatment comparisons. The study addresses the challenge of between-study heterogeneity by conducting random-effects analyses as sensitivity analyses. The study notes the challenge of evaluating comparative safety due to the lack of quantitative data.

    Comparative efficacy of AAC and ibuprofen versus lasmiditan, ubrogepant, and rimegepant for the acute treatment of episodic migraine in adults: a systematic review and network meta-analysis · 2026 · DOI

  • The network meta-analysis was limited to selected OTC therapies and newer oral agents, - The study did not synthesize comparative safety quantitatively, - The study was limited to acute episodic migraine

    Comparative efficacy of AAC and ibuprofen versus lasmiditan, ubrogepant, and rimegepant for the acute treatment of episodic migraine in adults: a systematic review and network meta-analysis · 2026 · DOI

  • Patients with chronic migraine often have comorbid conditions, such as anxiety and insomnia, which can impact treatment outcomes. Guanfacine may have potential side effects, such as hypotension and bradycardia, which require careful selection and monitoring. The need for further research to fully understand the mechanisms of guanfacine in chronic migraine prevention and to establish its efficacy and safety in clinical trials.

    Guanfacine as a potential preventive therapy for chronic migraine: a mechanistic hypothesis · 2026 · DOI

  • Limited treatment options for chronic migraine. Substantial proportion of patients failing to achieve meaningful benefit from existing therapies. Need for new, well-tolerated, and mechanistically distinct preventive treatments.

    Guanfacine as a potential preventive therapy for chronic migraine: a mechanistic hypothesis · 2026 · DOI

  • Investigate the long-term effects of diet quality on pediatric migraine - Examine the effectiveness of digital health education in improving diet quality and reducing headache burden - Develop standardized and actionable nutritional assessment and digital health education for pediatric migraine management

    Diet quality in pediatric migraine and the educational quality of related short-form videos: a cross-sectional study and content analysis · 2026 · DOI

  • Limited evidence on overall diet quality and related video quality in pediatric migraine management. Insufficient reliability and actionability of short-form videos on dietary management. A need for standardized and actionable nutritional assessment and digital health education in pediatric migraine management.

    Diet quality in pediatric migraine and the educational quality of related short-form videos: a cross-sectional study and content analysis · 2026 · DOI

  • There is a lack of head-to-head evidence against conventional preventive therapies in Chinese adults with chronic migraine. The cost-utility of erenumab preventive treatment for chronic migraine in China is unknown.

    Cost-utility analysis of erenumab preventive treatment for chronic migraine in China · 2026 · DOI

  • Background: The role of calcitonin gene-related peptide (CGRP) and inflammatory pathways in migraine pathophysiology remains to be fully elucidated.

    Serum calcitonin gene-related peptide and inflammatory marker dynamics across the migraine attack cycle: A case-control analysis · 2026 · DOI

  • Although the pathogenesis of VSS remains incompletely understood, Current evidence increasingly suggests that VSS may represent a multisystem neuropsychiatric network disorder involving visual cortical hyperexcitability, thalamocortical dysrhythmia, widespread abnormalities in functional connectivity, and limbic system dysfunction.

    Visual snow syndrome as a neuropsychiatric network disorder: clinical features, mechanisms, and therapeutic perspectives · 2026 · DOI

  • Background Dizziness, vertigo, and related autonomic symptoms are common in migraine, but whether their combined symptom-frequency burden is associated with hypothalamic subregional structure remains unclear.

    Hypothalamic subregional volume in relation to VSS-C total symptom burden in women with migraine: an exploratory cross-sectional MRI study · 2026 · DOI

  • BACKGROUND AND OBJECTIVES: Calcitonin gene-related peptide (CGRP) inhibitors have entered widespread use in the United States for treatment of migraine, but data on their cardiovascular risk profile are lacking.

    Calcitonin Gene–Related Peptide Inhibitors and Cardiovascular Events in Patients With Migraine · 2026 · DOI

  • However, the existing evidence is limited by small samples, use of suboptimal statistical thresholds, and different methods of clinical data acquisition.

    Unveiling Resting-State Functional Connectivity Patterns in Patients With Migraine · 2026 · DOI

  • BACKGROUND AND OBJECTIVES: Migraine activity is shaped not only by the biological vulnerability but also by environmental factors that may influence susceptibility and contribute to fluctuations in migraine occurrence, although the evidence remains inconsistent.

    Acute Environmental Triggers and Intermediate-Term Modulators of Emergency Migraine-Related Health Care Encounters · 2026 · DOI

  • Although these findings support a layered model of environmental modulation of migraine activity, their generalizability is limited by the use of emergency health care encounters as a proxy outcome, underscoring the need for further research using complementary measures.

    Acute Environmental Triggers and Intermediate-Term Modulators of Emergency Migraine-Related Health Care Encounters · 2026 · DOI

  • However, little is known about healthcare providers' (HCPs) attitudes and prescribing practices regarding STP.

    Healthcare providers’ perceptions and prescribing behaviors of short-term prevention treatment of migraine in the United States · 2026 · DOI

  • While clinical trials and real-world data suggest a favorable cardiovascular (CV) safety profile, particularly in patients without major risk factors, evidence remains limited for those with established vascular disease or recent vascular events.

    CGRP-Targeted Migraine Therapies in Patients With Vascular Risk Factors or Stroke · 2025 · DOI

  • Remission onset does not peak at a specific age, and disease duration varies widely between patients with remission.

    Exploration of Prolonged Remission and the Natural Course of Cluster Headache · 2025 · DOI

  • BACKGROUND AND OBJECTIVES: The long-term reproductive safety of migraine medications remains uncertain.

    Association of Prenatal Exposure to Triptans, Alone or Combined With Other Migraine Medications, and Neurodevelopmental Outcomes in Offspring · 2025 · DOI

  • BACKGROUND AND OBJECTIVES: Although obesity is recognized as a risk factor of migraine chronification, its longitudinal impact on migraine onset remains unclear.

    Association Between Obesity and the Risk of Migraine · 2025 · DOI

  • The potential effects of erenumab, a CGRP receptor antagonist monoclonal antibody, in treating CCH have not been assessed.

    Erenumab for Chronic Cluster Headache · 2025 · DOI

  • The study also revealed that while reports of AEs involving liver diseases were scarce across the three gepants, severe AEs were detected in clinical trials, highlighting the need for continued, enhanced monitoring of liver system AEs through large-scale datasets.

    Real-world study of adverse events associated with gepant use in migraine treatment based on the VigiAccess and U.S. Food and Drug Administration’s adverse event reporting system databases · 2024 · DOI

  • Nonetheless, comprehensive real-world studies on the safety of gepants are still lacking, particularly regarding their safety in large populations, long-term use, and potential adverse reactions in specific groups, which necessitates further empirical research.

    Real-world study of adverse events associated with gepant use in migraine treatment based on the VigiAccess and U.S. Food and Drug Administration’s adverse event reporting system databases · 2024 · DOI

  • Background: Specific antimigraine medications (dihydroergotamine (DHE), triptans) have been associated with adverse pregnancy outcomes in individual studies but lack of consensus remains.

    Anti-migraine medications safety during pregnancy in the US · 2024 · DOI

  • While certain dietary triggers have been identified, the impact of overall diet quality on migraine severity and frequency is not well understood.

    Investigating the relationship between diet quality, lifestyle and healthy eating index with severity and migraine attacks: a cross-sectional study · 2024 · DOI

  • It remains unclear, however, how the gut microbiota and migraines are causally related.

    To analyze the relationship between gut microbiota, metabolites and migraine: a two-sample Mendelian randomization study · 2024 · DOI

Most-cited papers in Migraine and Headache Studies

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208 open questions have been extracted from the limitations and future-work passages of 745 Migraine and Headache Studies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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