Clinical, behavioral, and metabolic determinants of migraine chronification: a systematic review
Year: 2026
Type: article
Study design: Systematic Review
Abstract: Introduction Migraine is a highly prevalent and potentially progressive neurological disorder, whose chronification—defined as the transition from episodic to chronic forms—poses a major clinical challenge. Multiple risk factors, particularly modifiable ones such as high attack frequency, inadequate management, and comorbid conditions, play a central role in this process and are critical targets for preventive strategies. Objective To evaluate clinical, behavioral, and metabolic risk factors associated with migraine chronification, with emphasis on modifiable determinants and their impact on disease progression. Methods This systematic review included studies retrieved from PubMed and LILACS databases using the descriptors “Risk Factors,” “migraine,” and “chronification” combined with the Boolean operator AND, yielding 84 records. The research question was structured using the PICO framework: in patients with episodic migraine (P), does exposure to modifiable risk factors and triggers (I), compared with non-exposure (C), increase the risk of migraine chronification, defined by higher attack frequency and disability (O). Studies published between 2021 and 2026, with full-text availability and in English, were considered eligible. After applying inclusion and exclusion criteria, 17 studies were selected for full analysis. Results Migraine chronification was predominantly associated with modifiable factors. Medication overuse emerged as a major determinant, increasing the risk of progression by up to threefold (OR≈3.0). Higher baseline attack frequency and disability were also strongly linked to chronification (OR≈2.08 for high disability). Psychiatric comorbidities, including depression (OR≈1.33–1.42) and anxiety (OR≈1.24), showed increasing prevalence with rising attack frequency. Additional contributors included allodynia, greater interictal burden, multiple pain-related comorbidities (OR≈1.24–1.30), and increased body adiposity, which was associated with up to a 2.8-fold higher risk. Behavioral factors such as stress, insomnia, smoking, and physical inactivity were also related to increased attack frequency. Conversely, preventive therapies demonstrated a protective effect (OR≈0.69–0.82), underscoring the relevance of prevalent and modifiable epidemiological factors in disease progression. Conclusion Migraine chronification is strongly associated with modifiable risk factors, particularly medication overuse, high attack frequency, and psychiatric comorbidities, highlighting the importance of early identification. Targeted strategies focusing on optimized treatment and lifestyle modifications are essential to prevent disease progression and mitigate its clinical burden.
Authors: Ellen Fernanda Lima de Souza, Beatriz Mascarenhas Nunes, Emilly Santos Oliveira, Júlia Batista Andrade Barreto, Felipe Vilanova de França Santana, Maria Clara Gama Carregosa, Danna Eduarda Macêdo Oliveira, Ádila Fernanda Pereira Martins, Giovana Oliveira Nascimento, Vitória Petri Rosa Santos Silva, Ana Júlia Britto Bomfim, Ana Marcela Ribeiro Rodrigues, Lara Marina Correia Lima, Giselle de Carvalho Neder, Renan Guedes de Britto
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7216901682