Definition

The diagnostic criteria of status migrainosus according to the International Classification of Headache Disorders (ICHD-3):


  • A. A headache attack fullfilling criteria B and C
  • B. Occuring in a patient with known migraine with aura or migraine without aura and typical of previous attacks except for its duration and severity
  • C. Both of the following characteristics must be present:
    1. Unremitting for > 72 h (but remissions of up to 12 h due to medication or sleep can be accepted)
    2. Pain and/or associated symptoms are debilitating
  • D. Not better accounted for by another ICHD-3 disorder

Evaluation

The diagnosis is clinical. Carefully exclude secondary causes to the headache (see Red flags in headache diagnosis). Neuroimaging studies and laboratory tests should be considered if there is suspicion of a secondary cause, if the symptoms are atypical or other “red flags” exist.


Outpatient treatment

  • Status migrainosus can by definition only be confirmed after 72 h of persistent symptoms, but the treatment should be initated earlier.
  • Rescue medication aims to eliminate the pain and associated symptoms with minimal side-effects.
  • Resolution of symptoms or improvement within 2 hours from administration is considered good control, after which the patients are often instructed to repeat the rescue medication.
  • There are no evidence based guidelines for treatment when the symptoms persist > 4 h.
  • Ensure proper hydration, which should include both electrolyte-containing water supplements and free water.
  • Use a stratified treatment strategy, starting with NSAIDs for milder attacks and moving to migraine-specific medication (triptans, gepants, or ditans) for moderate to severe attacks.
  • Using combination treatments from the start of an attack that is severe from onset and has a high risk of progressing in status migrainosus is justified.

  1. Non-steroidal antiinflammatory drugs:
    • Naproxen 500 mg p.o.
    • Diclofenac 50 mg p.o.
    • Ibuprofen 600-80 mg p.o.
    • Ketoprofen 75 mg p.o.
    • Piroxicam 20 mg p.o.
    • Indomethacin 50 mg p.o.
    • Ketorolac 10 mg p.o

  1. Analgesics
    • Paracetamol 500-1000 mg p.o.

  1. Triptans
    • Sumatriptan 100 mg p.o. or 20 mg IN or 3, 4 or 6 mg IM
    • Zolmitriptan 5 mg p.o. or IN
    • Rizatriptan 10 mg p.o.
    • Dihydroergotamine (DHE) 1 mg SC
    • Naratriptan 2.5 mg p.o.
    • Frovatriptan 2.5 mg p.o.
    • Eletriptan 40 mg p.o.
    • Almotriptan 12.5 mg p.o.

  1. Gepants or ditans
    • Rimegepant 75 mg p.o.
    • Ubrogepant 50/100 mg p.o.
    • Lasmiditan1 50/100/200 mg p.o.

  1. Antiemetics
    • Ondansetron 4-8 mg p.o.

  1. Antidopaminergics2
    • Metoclopramide 10 mg p.o. or IM
    • Prochlorperazine 10 mg p.o. or IM
    • Chlorpromazine 25 mg p.o.
    • Olanzapine 10 mg p.o.
    • Haloperidol 2.5-5 mg p.o.

  1. Antihistamines
    • Hydroxyzine 25-100 mg p.o.
    • Diphenhydramine 25-50 mg p.o.

  1. Antiepileptics
    • Divalproex 250 mg p.o.
    • Gabapentin 300-900 mg p.o.

  1. Corticosteroids
    • Dexamethasone 4 mg p.o. every 12 h for 4 days
    • Methylprednisolone
    • Prednisone

  1. Magnesium
    • 500-1000 mg/day in 1 or 2 doses

  1. Muscle relaxants
    • Cyclobenzaprine 5-10 mg p.o.
    • Tizanidine 2-8 mg p.o.
    • Baclofen 5-10 mg p.o.

  1. Timolol
    • 0.25% eydrops, 1 drop/eye for 5 days

  1. CRGP inhibitors
    • Erenumab 70 or 140 mg/month SC
    • Fremanezumab 225 mg/month or 675 mg/quarter SC
    • Galcanezumab 240 mg loading dose SC followed by 120 mg/month SC

1 Risk for serotonin syndrome when co-administered with triptans. Do not co-administer with DHE. 2 Antidopaminergics should be administered with caution due to risk for extrapyramidal effects. QT prolongation should be ruled out by EEG before administration.

In-clinic treatment options

If at-home treatments have failed to control symptoms.


  1. 100% oxygen 12-15L using Non-rebreather mask
  2. Normal saline 1-2L IV
  3. Dihydroergotamine 1 mg SC
  4. Prochlorperazine 10 mg IM
  5. Metoclopramide 10 mg IM
  6. Promethazine 25 mg p.o. or IV or IM
  7. Chlorpromazine 12.5-25 mg IV
  8. Diphenhydramine 12.5-25 mg IV
  9. Ketorolac 30-60 mg IV or IM
  10. Paracetamol 1000 mg IV
  11. Magnesium sulfate 1 mg IV
  12. Steroids
    • Dexamethasone 4-24 mg IV
    • Methylprednisolone 100-200 mg IV
  13. Ondansetron 4 mg IV
  14. Eptinezumab 100-300 mg IV
  15. Nerve blockade (1% lidocaine or 0.5% bupivicaine)
    • Supraorbital
    • Supratrochlear
    • Auriculotemporal
    • Greater and lesser occipital
    • Sphenopalatine ganglion


References

  • Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211.
  • GBD Headache Collaborators 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 [published correction appears in Lancet Neurol. 2021 Dec;20(12):e7]. Lancet Neurol. 2018;17(11):954-976. doi: 10.1016/S1474-4422(18)30322-3
  • Headache at the emergency room: etiologies, diagnostic usefulness of the ICHD 3 criteria, red and green flags. PLoS One. 2019;14(1):e0208728 doi: 10.1371/journal.pone.0208728
  • Status migrainosus and migraine aura status in a French tertiary-care center: an 11-year retrospective analysis. Cephalalgia. 2014;34(8):633-637
  • Lasmiditan mechanism of action - review of a selective 5-HT1F agonist. J Headache Pain. 2020;21(1):71
  • Comparison of new pharmacologic agents with triptans for treatment of migraine: a systematic review and meta-analysis. JAMA Netw Open. 2021;4(10):e2128544 doi: 10.1001/jamanetworkopen.2021.28544