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Table 1 Overview of the published proposal for refractory or intractable migraine

From: Identifying and managing refractory migraine: barriers and opportunities?

  Goadsby et al. (2006) Schulman et al. (2008) Silberstein et al. (2010) Martelletti et al. (2014)
Headache Diagnosis
 Diagnostic criteria Not stated ICHD diagnostic criteria ICHD diagnostic criteria ICHD diagnostic criteria
 Episodic or Chronic Migraine Not stated Both included Inclusion of both episodic and chronic migraine not explicitly stated but implicitly included as criteria pertain to all primary headaches Limited to chronic migraine
 Medication overuse Not stated With or without medication overuse (as defined by ICHD criteria) included as modifier Not stated No medication overuse
Acute Treatments
 Inclusion in operational criteria Criteria limited to preventive treatments only Included in refractoriness criteria Included in refractoriness criteria Criteria limited to preventive treatments only
 Number of acute treatments failed Not applicable Both of the following 2 classes Grading system proposed:
Mild: failed class1
Moderate: failed classes 1–3
Severe: failed classes 1–4
Not applicable
 Acute classes Not applicable 1. Both a triptan and DHE intranasal or injectable formulation
2. Either nonsteroidal anti-inflammatory drugs or combination analgesics
1. Non-specific acute treatments (eg, NSAIDs, combination analgesics)
2. Triptans or ergot derivatives
3. Oral dopamine antagonists or parenteral NSAID
4. Oral or parenteral opioids or corticosteroids or parenteral dopamine antagonists
Not applicable
Preventive treatments
 Number of classes failed 4 classes (including 3 from 1 to 4) 2 of 4 classes: Grading system proposed:
Mild: failed 1 of cases 1–10
Moderate: failed 2 drugs where 1 must be from classes 1–6
Severe: failed 3 drugs where 2 must be from classes 1–6
Very severe: Above plus failed aggressive infusion or inpatient treatment and/or failure to respond to detoxification treatment in subjects with acute headache pain medication overuse
3 drugs from following classes
 Preventive classes 1. Beta-blockers
2. Anticonvulsants
3. Calcium channel blockers
4. Tricyclic antidepressants
5. Other treatments with at least one positive randomised controlled trial
6. Non-steroidal anti-inflammatory drugs
7. Metabolic enhancers
1. Beta-blockers
2. Anticonvulsants
3. Tricyclics
4. Calcium channel blockers
1. Beta-blockers (shown to be effective)
2. Tricyclic antidepressants
3. Verapamil or flunarizine
4. Sodium valproate (or divalproex sodium)
5. Topiramate
6. Combination therapy that includes at least 1 drug of type 1–5; the second drug can be from any type (1-5 or 6-9). The drugs must be of different types (eg, a combination of 2 anticonvulsants is not acceptable)
7. Gabapentin
8. Other treatments with at least 1 positive placebo-controlled trial
9. Non-steroidal anti-inflammatory drugs
10. Metabolic enhancers (Vitamin B2 or CoQ10)
1.Beta blockers (propranolol up to 240 mg/d; metoprolol up to200mg; atenolol up to100mg; bisoprolol up to10mg)
2.Anticonvulsants (valproate acid up to 1,5 g/d; topiramate up to 200 mg/d)
3.Tricyclics (amitriptyline up to 150 mg/d)
4.Others (flunarizine up to 10 mg/d; candesartan 16 mg/d)
5.OnabotulinumtoxinA (155–195 U according to the PREEMPT protocol)
Headache-Related Disability Disabled by standard scales e.g. MIDAS, HIT-6 or scale suitable in country of assessment Included as a modifier, with patients classified as having significant disability if MIDAS > 11 Disability measured using MIDAS or HIT-6 Not included
Lifestyle factors Not addressed Criteria state that headaches should cause “significant interference with function or quality of life despite modification of triggers, and lifestyle factors” but no operational criteria provided Considered by authors but excluded Not included
Comorbidities Not addressed Not addressed Considered by authors but excluded Adequate treatment of psychiatric or other comorbidities by multidisciplinary team, if available.
Definition of failed trial No therapeutic or unsatisfactory effecta
Intolerable side effects
Contraindications to use
Not defined Not defined No therapeutic effecta
Contraindications to use
Definition of adequate trials Appropriate dosea
Appropriate durationa
Period of time during which an appropriate dose of medicine is administered, typically at least 2 months at optimal or maximum tolerated dose, unless terminated early due to adverse effects Not defined Prophylactic migraine medications in adequate dosages used for at least 3 months each.
  1. DHE Dihydroergotamine, HIT-6 Headache Impact Test, ICHD International Classification of Headache Disorders, MIDAS Migraine Disability Assessment Test
  2. aNot further defined
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