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Observational Study
. 2024 Dec 3;25(1):212.
doi: 10.1186/s10194-024-01910-3.

Resistant and refractory migraine - two different entities with different comorbidities? Results from the REFINE study

C Rosignoli  1 , R Ornello  1 , V Caponnetto  2 , A Onofri  1 , S Avaltroni  1 , M Braschinsky  3 , O Šved  3 , R Gil-Gouveia  4 , C Lampl  5 , J Paungarttner  5 , P Martelletti  6 , W D Wells-Gatnik  6 , I P Martins  7 , D Mitsikostas  8 , L Apostolakopoulou  8 , G Nabaei  9 , A Ozge  10 , D B Narin  10 , P Pozo-Rosich  11 , A Muñoz-Vendrell  11 , M P Prudenzano  12 , M Gentile  12 , K Ryliskiene  13 , J Vainauskiene  13 , M Sanchez Del Rio  14 , F Vernieri  15 , G Iaccarino  15 , M Waliszewska-Prosol  16 , S Budrewicz  16 , M Carnovali  17 , Z Katsarava  17 , S Sacco  18
Affiliations
Observational Study

Resistant and refractory migraine - two different entities with different comorbidities? Results from the REFINE study

C Rosignoli et al. J Headache Pain. .

Abstract

Background: Resistant and refractory migraine are commonly encountered in specialized headache centers. Several comorbidities, mostly psychiatric conditions, have been linked to migraine worsening; however, there is little knowledge of the comorbidity profile of individuals with resistant and refractory migraine.

Methods: REFINE is a prospective observational multicenter international study involving individuals with migraine from 15 headache centers. Participants were categorized into three groups based on the European Headache Federation criteria: non-resistant and non-refractory (NRNRM), resistant (ResM), and refractory (RefM). We explored the prevalence of 20 comorbidities at baseline in the three groups.

Results: Of the 689 included patients (82.8% women), 262 (38.0%) had ResM, 73 (10.4%) had RefM and 354 (51.4%) NRNRM. A higher prevalence of psychiatric comorbidities, trigger points, temporomandibular joint disorders, thyroiditis, and cerebrovascular diseases was observed in the RefM group, followed by ResM and NRNRM. Multiple comorbidities were more common in the RefM group, followed by the ResM group and by the NRNRM group (41.6% vs. 24.5% vs. 14.1% respectively; p < 0.001). At the sensitivity analysis, exploring participants with chronic migraine, significant differences among the NRNRM, ResM, and RefM groups were found in the prevalence of anxiety (p < 0.001), asthma and rhinitis (p = 0.013), bipolar and other psychiatric disorders (p = 0.049), cerebrovascular diseases (p < 0.001), depression (p < 0.001), obesity (p = 0.002), thyroiditis (p < 0.001), and trigger points (p = 0.008).

Conclusion: REFINE data indicate that individuals with ResM and RefM have a higher burden of comorbidities than those with NRNRM. It can be postulated that those comorbidities may have an impact on the progression of migraine from a form that is easy to treat to a form that is resistant or refractory to treatments. Longitudinal studies are needed to understand the direction of the association between ResM or RefM and those comorbidities and if proper treatment of comorbidities might help overcome treatment resistance or refractoriness.

Keywords: Comorbidities; Migraine; Refractory migraine; Resistant migraine.

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Conflict of interest statement

Declarations. Competing interests: P.M. serves as the Editor-in-Chief of The Journal of Headache and Pain.

Figures

Fig. 1
Fig. 1
Prevalence of comorbidities according to the diagnosis of resistant, refractory, or non-resistant migraine in the overall REFINE cohort
Fig. 2
Fig. 2
Prevalence of multiple comorbidities
Fig. 3
Fig. 3
Prevalence of comorbidities according to the diagnosis of resistant, refractory, or non-resistant migraine in the subset of participants with chronic migraine
See this image and copyright information in PMC

References

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