Acute Migraine Headache Medication

Aka: Acute Migraine Headache Medication, Migraine Abortive Medication, Migraine Abortive Treatment, Migraine Abortive Management

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II. Management: General Pointers

  1. Follow a stepped strategy of Migraine medication
    1. See Acute Migraine Headache
  2. Consider abortive agent sparing measures
    1. See Headache General Measures
    2. See Migraine Prophylaxis
    3. Establish Migraine Management Clinic Schedule
    4. Consider Migraine Headache Prophylaxis
      1. Frequent Migraine Headaches (4/month, 8 days/month)
      2. Prolonged Headaches >2 days with Disability
      3. Debilitating Headache despite acute Migraine abortive agents
      4. Intolerance or contraindications to acute Migraine abortive agents
      5. Analgesic Overuse Headaches or overuse of acute Migraine abortive agents
      6. Complicated Migraine Headache subtypes with prominent neurologic findings
  3. Evaluate acute Headache regimen with standardized symptom score
    1. Migraine Treatment Optimization Questionnaire (M-TOQ)
      1. https://www.mdcalc.com/calc/10496/migraine-treatment-optimization-questionnaire-mtoq-4
      2. Lipton (2009) Cephalalgia 29(7):751-9 [PubMed]
      3. Serrano (2015) Headache 55(4):502-18 [PubMed]
    2. Migraine Assessment of Current Therapy (Migraine-ACT)
      1. Dowson (2004) Neurol Sci 25 Suppl 3:S276-8 +PMID:15549559 [PubMed]
      2. Kilminster (2006) Headache 46(4):553-62 [PubMed]
  4. Avoid overuse of abortive agents
    1. Frequent use results in Rebound Headache
    2. Limit Analgesics and NSAIDs to 3 days per week and 10 days per month
    3. Limit Triptans and combined Analgesics to 2 days per week and 8 days per month
  5. Most medications (e.g. Triptans, NSAIDs) are not effective in the prodrome or aura phase of Migraine Headache
    1. However, Ubrogepant (Ubrelvy, CGRP receptor blocker) may be effective during this phase
  6. Recurrent Migraine Headache within first 48 hours (40% of patients)
    1. See Emergency Department Migraine Headache Care
    2. Repeat dose of Triptan
    3. Combine Triptan with a longer acting Triptan
    4. Consider longer acting Triptans (e.g. Naratriptan, Frovatriptan)
      1. May have reduced initial efficacy (slower onset)
  7. Adjust management for specific cohorts
    1. Children
      1. See Migraine Headache Management in Children
    2. Pregnancy and Lactation
      1. See Headache in Pregnancy
      2. See Migraine Medications in Pregnancy
      3. See Migraine Medications in Breast Feeding
    3. Older adults
      1. Acetaminophen (limit to <3 grams/day)
      2. Use NSAIDS only with caution (avoiding in most patients age >65-70 years)
      3. Triptans may be used if no significant vascular disease history
      4. Consider Gepants (review potential Drug Interactions, including with CYP3A4 inducers)

III. Medications: Serotonin Agonists

  1. See Acute Migraine Headache
  2. Triptans may have inadequate response in up to one third of Migraine Headache patients
    1. Triptans may be less effective in Menstrual Migraine and sleep onset Migraine
    2. Improving Triptan efficacy
      1. Triptans are most effective when taken earlier in Migraine course
      2. Triptans are more effective when combined with a fast release NSAID formulation (e.g. Naproxen)
    3. Efficacy of a given Triptan is based on its success of treating 3-4 consecutive Migraine Headaches
      1. Switching to another Triptan may be considered when a Triptan fails for 2-3 consecutive Migraines
    4. Increasing Triptan dose may moderately improve effect with some Triptans
      1. Sumatriptan and Eletriptan may be more effective at higher dose
      2. Zolmitriptan efficacy does not appear to improve with dosing increase
    5. Consider Rebound Headache or other Headache Causes
    6. Consider third-line agents (see below)
  3. Triptans (far preferred, have replaced Ergotamines)
    1. Sumatriptan (Imitrex)
    2. Rizatriptan (Maxalt)
    3. Zolmitriptan (Zomig)
    4. Naratriptan (Amerge)
  4. Ergotamines (do not use within 24 hours of Triptans)
    1. Rarely used in modern U.S. Migraine Management (largely replaced by Triptans)
      1. Low oral Bioavailability
      2. High risk for Medication Overuse Headache
      3. Common associated Nausea and Vomiting
      4. Serious adverse Drug Interaction risk
    2. Ergotamine Agents
      1. Dihydroergotamine (DHE-45)
      2. Ergotamine

IV. Medications: Oral Analgesics

  1. See Acute Migraine Headache
  2. General
    1. Beware Rebound Headaches with the frequent use of most Analgesics
  3. Analgesics with proven efficacy
    1. Excedrin Migraine (Acetaminophen, Aspirin, Caffeine)
    2. Aspirin 975 mg PO (with or without Metoclopramide)
    3. Midrin (Isometheptene, Dichloralphenazone, Tylenol)
      1. Dose: 2 stat at Headache onset
      2. Repeat 1 each hour prn
      3. Maximum: 5 pills per 12 hours, 20 pills per month
      4. Limit use to no more than 2 days per week
    4. Anaprox, Aleve (NaproxenSodium)
      1. Absorbed more rapidly than Naprosyn
      2. Initial Dose: 825 mg (Three 275 mg tablets)
      3. Repeat 220 to 550 mg every 3-4 hours
      4. Maximum: 1.5 grams per day (5 to 6 tablets per day)
  4. Combined therapies may be helpful in refractory cases
    1. Aspirin (or NSAID) and Metoclopramide
      1. Aspirin 975 mg PO (three 325 mg tablets)
      2. Metoclopramide (Reglan) 10 mg PO
    2. DHE and Vistaril Combination (rare use)
      1. DHE-45 1 mg IM
      2. Vistaril 75 mg IM
  5. Analgesics to be avoided (low efficacy and higher risk)
    1. Cafergot (Ergotamine with Caffeine)
      1. Dose: 2 PO stat with Headache onset
      2. Repeat one tablet every half hour prn
      3. Maximum: 4 to 6 pills per day or 10 per week
    2. Fiorinal (ASA 325mg, Caffeine 40mg, Butalbital 50mg)
      1. Dose: 2 tablets at Headache onset
      2. Repeat one tablet every 4 to 6 hours prn
      3. Maximum: 5 pills per day or 15 per month
      4. Limit use to no more than 2 days per week
      5. Risk of Rebound Headaches with use more than 5 days per month
    3. Esgic or Fioricet (Tylenol, Caffeine, Butalbital)
      1. Same dosing recommendations and precautions as for Fiorinal
      2. Precaution: Pharmaceutical obfuscation alert
        1. Fioricet brand name capsules (Watson) as of 2014 will contain 300 mg Acetaminophen (at 4x the generic cost)
        2. Fioricet generic tablets will contain 325 mg Acetaminophen (making automatic substitution difficult)
        3. One more reason not to prescribe fioricet (other Migraine abortive agents are preferred)
        4. (2014) Presc Lett 21(3)

V. Medications: DopamineAntagonist Antiemetics

  1. See Emergency Department Migraine Headache Care
  2. Antiemetics may be very useful in abortive treatment
    1. Alleviate Nausea associated with Headache
    2. Sedation to allow rest despite Headache
    3. Anti-Dopaminergic effects are very effective in Migraine Headaches
  3. Metoclopramide (Reglan)
    1. Mechanism
      1. Antiemetic
      2. Dopamine Antagonist effects on Migraine Headache
      3. Increases castrointestinal motility (and Analgesic absorption)
    2. Dose: 10 mg PO 20-30 minutes before pre-medication
    3. Extrapyramidal Side Effects
      1. Dystonic Reaction (especially in children)

VI. Medications: ParenteralAnalgesics

  1. See Emergency Department Migraine Headache Care
  2. See Serotonin Agonists (Triptans) below
  3. See Opioids below (avoid if possible)
  4. Ketorolac (Toradol)
    1. Dose: 30-60 mg IM
    2. May repeat 15-30 mg q6h
    3. Do not exceed 5 consecutive days of use
    4. May supplement with rectal Antiemetic

VII. Medications: Rectal Analgesics (indicated for Vomiting)

  1. Rectal Antiemetics
    1. Promethazine (Phenergan) 12.5 to 25 mg PR q4-6 hours
    2. Prochlorperazine (Compazine) 25 mg PR q12 hours
  2. Rectal Analgesics
    1. Indomethacin 50 mg, 1-2 PR at Headache onset
  3. Serotonin Agonist
    1. Ergotamine tartrate (Wigraine) suppository
    2. Use Ergotamine with caution due to adverse effects

VIII. Medications: Third-line Agents

  1. Precautions
    1. Expensive agents ($85 per tablet in 2020)
    2. Half the efficacy of Triptans
  2. Indications
    1. Indicated in Migraines refractory to at least two first-line Triptans
    2. Evaluate efficacy with standardized symptom score (see above)
  3. Benefits
    1. May be less likely to cause overuse Headache
    2. May be effective during Headache prodrome or aura (while Triptans and NSAIDs are not)
  4. Gepant (CGRP receptor blocker)
    1. Ubrogepant (Ubrelvy)
    2. Rimegepant (Nurtec)
    3. Zavegepant (Zavzpret)
  5. Ditan (Selective Serotonin 5-Hydroxytryptamine receptor 1F agonst or 5-HT1F Agonist)
    1. Schedule V due to euphoria and Hallucinations
    2. Lasmiditan (Reyvow)

IX. Medications: Opioids

  1. Generally avoid Opioids in chronic Headache Management
  2. Indications
    1. Patients failing every other non-Opioid therapy and Migraine Prophylaxis despite neurology Consultation
    2. Least desirable for Headache Management
      1. Non-specific for Headache
      2. Higher risk for Rebound Headache
      3. Addictive potential (Substance Misuse)
  3. Stadol-NS (Butorphanol)
    1. Addictive (Class IV regulated substance)
      1. High abuse potential
    2. Dosing
      1. Stadol 1 spray in one nostril, repeat hourly prn
      2. Maximum 4 sprays per day or 6 sprays per week
      3. Limit to 2 days per week

X. Medications: Other Non-Pharmacologic Measures

  1. Greater Occipital Nerve Block
  2. Neuromodulatory Devices
    1. Noninvasive Vagus Nerve stimulation
    2. Remote electrical neuromodulation
  3. Avoid measures without strong evidence in acute Migraine Management
    1. Acupuncture
    2. Electrical Trigeminal Nerve stimulation
    3. Single-Pulse transcranial magnetic stimulation

XI. Contraindications: Vasocontrictors (e.g. Triptans, DHE)

  1. Contraindications to Vasoconstrictors (e.g. Triptan, DHE)
    1. Coronary Artery Disease
    2. Cerebrovascular Accident history
    3. Hemiplegic Migraines
    4. Basilar Migraines
    5. Pregnancy
  2. Alternative Non-Vasoconstrictive agents
    1. Excedrin Migraine (Acetaminophen, Aspirin, Caffeine)
    2. NSAIDS
    3. Dopamine Antagonists (e.g. Metoclopramide or Prochlorperazine)
    4. Gepant (CGRP receptor blocker, e.g. Ubrogepant, Rimegepant, Zavegepant)
    5. Ditan (e.g. Lasmiditan)

XII. References

  1. (1995) Med Lett Drugs Ther 37(943) [PubMed]
  2. Moore (1997) Am Fam Physician 56(8):2039-48 [PubMed]
  3. Jackson (1998) CMEA Internal Medicine Lecture,San Diego
  4. Noble (1997) Am Fam Physician 56(9):2279-86 [PubMed]
  5. Puledda (2024) Cephalgia 44(8): 3331024241252666 [PubMed]
  6. Wiley (2025) Am Fam Physician 111(4): 317-27 [PubMed]

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