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

 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

 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

 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 effect^a

Intolerable side effects

Contraindications to use

Not defined

Not defined

No therapeutic effect^a

Contraindications to use

Definition of adequate trials

Appropriate dose^a

Appropriate duration^a

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.