European headache federation consensus on the definition of resistant and refractory migraine

DOI: https://doi.org/10.1186/s10194- 020- 01130- 5

Abstract-Summary Despite advances in the management of headache disorders, some patients with migraine do not experience adequate pain relief with acute and preventive treatments. It is the aim of the present document to provide a definition of those migraines which are difficult-to-treat, to create awareness of existence of this group of patients, to help Healthcare Authorities in understanding the implications, and to create a basis to develop a better pathophysiological understanding and to support further therapeutic advances.

Patients with migraine with or without aura or with chronic migraine can be defined as having resistant migraine and refractory migraine according to previous preventative failures.

Resistant migraine is defined by having failed at least 3 classes of migraine pre- ventatives and suffer from at least 8 debilitating headache days per month for at least 3 consecutive months without improvement; definition can be based on review of medical charts.

Refractory migraine is defined by having failed all of the available preventatives and suffer from at least 8 debilitating headache days per month for at least 6 con- secutive months.

Only with a widely accepted definition, progresses in difficult-to-treat migraine

can be achieved.

It is the hope of the EHF Expert Consensus Group that the proposed criteria will stimulate further clinical, scientific and social attention to patients who suffer from migraine which is difficult-to-treat.

Extended: It is the hope of the EHF Expert Consensus Group that the proposed criteria will stimulate further clinical, scientific and social attention to patients who suffer from migraine which is difficult-to-treat.

Only with a widely accepted definition, progresses in difficult-to-treat migraine can be achieved, underlying mechanisms can be identified, epidemiology can be characterized, and evidence-based treatments can be developed.

Introduction Despite advances in the management of headache disorders, some patients with migraine do not experience adequate pain relief with acute and preventive treatments. A previous consensus statement of the European Headache Federation (EHF) defined as refractory migraine those chronic migraine patients who do not show response to adequate dosages of at least 3 drugs from the following classes: beta- blockers, anticonvulsants, tricyclics, onabotulinumtoxinA and others (e.g., flunari- zine, candesartan) for at least 3 months each, in absence of medication overuse [1]. The aim of the present Consensus paper is to critically revise the definition of those migraines which are difficult-to-treat, to create awareness of existence of this

3.1 Classification

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group of patients, to help Healthcare Authorities in understanding the implications, and to create a basis to develop a better pathophysiological understanding and to support further therapeutic advances.

Methods The Panel who developed this consensus statement consisted of the members of the Council of the EHF.

Patients representatives were not involved in the consensus process to develop

the definitions but had the opportunity to provide suggestions and comments.

This Consensus represents an update of a previous EHF consensus published in

2014 [1].

All the points of the previous EHF consensus definition were reconsidered by the

EHF Expert Consensus Group and revised if necessary.

An in-person meeting was held to agree on the need of a new Consensus Statement, on the composition of the EHF Expert Consensus Group and on the mis- sion of this updated Consensus Statement.

According to this method, the EHF Expert Consensus Group members were

assigned to open or multiple-choice questions in several rounds.

Results Resistant migraine is defined by having failed at least 3 classes of migraine preven- tatives and suffer from at least 8 debilitating headache days per month for at least 3 consecutive months without improvement; definition can be based on review of medical charts.

Refractory migraine is defined by having failed all of the available preventatives and suffer from at least 8 debilitating headache days per month for at least 6 con- secutive months.

The presence of medication overuse is compatible with the proposed definition of resistant and refractory migraine; however, in patients with refractory migraine documentation of failed attempts of withdrawal of medications is needed.

Both definitions of resistant and refractory migraine require the presence of at

least 8 days of debilitating migraine.

To validate the definitions, it is also recommended that patients with resistant migraine are evaluated by headache specialists and that patients with refractory migraine are evaluated in tertiary Headache Centers.

Discussion One of the major novelties of the updated EHF Consensus definition is the recogni- tion that difficult-to-treat patients may be labelled into two major categories, resis- tant migraine and refractory migraine; the difference between resistant and refractory migraine relies on the number of required previous treatment failures.

We duly recognize that patients who also do not meet criteria for resistant migraine (e.g. 6 debilitating migraine days per month) may need access to dedicated headache care or treatment escalation.

With the use of cut-off values, patients who have significant response to treat- ment (e.g. a patient with 30 headache days per month and with > 50% reduction in headache days with treatment) may be labelled as resistant or refractory.

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3 Diagnosis

In the current EHF definitions of resistant and refractory migraine, we did not include in the criteria the possibility to combine different preventatives to achieve a response to treatment in the criteria.

Conclusion The proposed updated EHF definition identifies two subsets of difficult-to-treat migraine, resistant and refractory migraine, and considers both frequency and dis- ability from single and frequent attacks.

Although, in the previous literature formal and operational definitions for refrac-

tory or intractable headache were proposed, none was universally accepted.

Only with a widely accepted definition, progresses in difficult-to-treat migraine can be achieved, underlying mechanisms can be identified, epidemiology can be characterized, and evidence-based treatments can be developed.

It is the hope of the EHF Expert Consensus Group that the proposed criteria will stimulate further clinical, scientific and social attention to patients who suffer from migraine which is difficult-to-treat.

Acknowledgement A machine generated summary based on the work of Sacco, Simona; Braschinsky, Mark; Ducros, Anne; Lampl, Christian; Little, Patrick; van den Brink, Antoinette Maassen; Pozo-Rosich, Patricia; Reuter, Uwe; de la Torre, Elena Ruiz; Sanchez Del Rio, Margarita; Sinclair, Alexandra J.; Katsarava, Zaza; Martelletti, Paolo 2020 in The Journal of Headache and Pain.

Experts’ opinion about the primary headache diagnostic criteria of the ICHD-3rd edition beta in children and adolescents