Introduction
Historical perspective
Goadsby et al. (2006) | Schulman et al. (2008) | Silberstein et al. (2010) | Martelletti et al. (2014) | |
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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. |
Importance of defining refractory migraine
Nomenclature
Requirements for determining refractoriness
Headache diagnosis
Pharmacological treatment failure
Abortive or preventive treatments?
Which and how many preventive treatments?
Definition of an adequate trial
Definition of failed trial of preventive treatment
Non-pharmacological treatment failure
Headache-related disability
Refractory chronic migraine criteria: a personal perspective
Criteria | Definition |
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A. Primary Diagnosis | 1. ICHD-III chronic migraine 2. Medication overuse headache excludeda |
B. Refractory | Failure to respond to 5 classes of preventive treatments (including 2 from 1 to 3b): 1. Topiramate 2. Minimum of two quarterly injections of Onabotulinumtoxin A 3. CGRP pathway monoclonal antibody 4. Betablockers (Propranolol, Metoprolol, Timolol) 5. Tricyclic antidepressant (Amitriptyline) 6. SNRI (Venlafaxine) 7. Sodium valproate/Divalproex sodium 8. Other pharmacological preventive treatments with established efficacy in migrainec |
C. Adequate Trial | At least 2 month trial at an optimum or maximum tolerated dose (excluding the time taken for the titration o the dose), unless terminated early due to side effectsd |
D. Failed Trial | 1. Failure to respond to drug (< 50% reduction in frequency and/or severity of monthly migraine days) 2. Intolerable side effects 3. Contraindication to use |
Epidemiology
Pathophysiology
Management of Refractory Migraine
Review the diagnosis
Identify important exacerbating factors and comorbidities
Educate the patient about lifestyle factors
Consider biobehavioural therapies
Optimise pharmacotherapy
Oral/Nasal | Injectable | Neurostimulation | |
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Acute | • Oral and Intranasal Triptans • High dose NSAIDS • Paracetamol • Antiemetics | • Subcutaneous sumatriptan | • Transcranial magnetic stimulation • External trigeminal nerve stimulation (Cefaly) • Vagal nerve stimulation |
Preventive | • Beta-blockers: Propranolol, Metoprolol, Timolol, Atenolol, Nadolol • Anticonvulsants: Topiramate, Valproate • Tricyclics: Amitriptyline • SNRI: Venlafaxine • Angiotensin pathway blockers: Lisinopril, Candesartan • Calcium channel blockers: Flunarizine • Nutraceuticals: Riboflavin, Coenzyme Q10, Magnesium, Feverfew | • Onabotulinumtoxin A • CGRP-pathway monoclonal antibodies | • External trigeminal nerve stimulation (Cefaly) • Transcranial magnetic stimulation • Occipital nerve stimulation • High cervical spinal cord stimulation |
Transitional | • Corticosteroids | • Greater occipital nerve block • Multiple cranial nerve blocks • Intravenous dihydroergotamine • Intravenous lidocaine |