What are the classes of medications used to treat migraines, including their mechanisms of action, typical dosing, and side effects?

Migraine Treatment Classes: Mechanisms, Dosing, and Side Effects

For most migraine sufferers, nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line therapy for mild to moderate attacks, while triptans are first-line for moderate to severe attacks. 1

Acute Treatment Classes

First-Line Treatments

NSAIDs

• Mechanism of Action: Inhibit cyclooxygenase enzymes, reducing prostaglandin synthesis and inflammation 1
• Examples: Aspirin, ibuprofen, naproxen sodium, diclofenac potassium 1
• Typical Dosing:
  • Ibuprofen: 400-800mg every 6-8 hours as needed 1
  • Naproxen: 500-1000mg initially, then 250-500mg every 12 hours 2
  • Aspirin: 900-1000mg as needed 1
• Side Effects: Gastrointestinal bleeding/ulceration, renal impairment, increased cardiovascular risk with prolonged use 2
• Cautions: Avoid in patients with history of GI bleeding, heart disease, or renal impairment 2

Triptans (5-HT1B/1D agonists)

• Mechanism of Action: Activate serotonin receptors causing cranial vessel constriction and inhibition of vasoactive neuropeptide release from trigeminal nerve endings 3, 4
• Examples: Sumatriptan, rizatriptan, zolmitriptan, naratriptan, almotriptan, frovatriptan, eletriptan 1
• Typical Dosing:
  • Sumatriptan: 25-100mg orally, 6mg subcutaneously, 5-20mg intranasally 1
  • Rizatriptan: 5-10mg orally 1
  • Zolmitriptan: 2.5-5mg orally 1
• Side Effects: Chest/throat tightness, paresthesias, dizziness, fatigue, injection site reactions (with injectable forms) 4
• Contraindications: Ischemic heart disease, uncontrolled hypertension, hemiplegic or basilar migraine, within 24 hours of ergot derivatives 1, 3

Second-Line Treatments

Ergot Alkaloids

• Mechanism of Action: Non-selective serotonin receptor agonists causing vasoconstriction 1
• Examples: Dihydroergotamine (DHE), ergotamine with caffeine 1
• Typical Dosing:
  • DHE: 0.5-1mg IM/IV, can repeat hourly up to 3mg/day; intranasal: 0.5mg per nostril, may repeat after 15 minutes 1
  • Ergotamine with caffeine: 2 tablets (1mg ergotamine/100mg caffeine) initially, then 1 tablet every 30 minutes up to 6 tablets per attack 1
• Side Effects: Nausea, vomiting, peripheral vasoconstriction, ergot toxicity with overuse 1
• Contraindications: Cardiovascular disease, uncontrolled hypertension, pregnancy, concurrent use with triptans 1

Antiemetics

• Mechanism of Action: Dopamine antagonism in chemoreceptor trigger zone 1
• Examples: Metoclopramide, prochlorperazine, chlorpromazine 1
• Typical Dosing:
  • Metoclopramide: 10mg IV/IM/PO
  • Prochlorperazine: 5-10mg IV/IM or 25mg PR
• Side Effects: Sedation, akathisia, extrapyramidal symptoms, QT prolongation 1

Newer Agents

• Gepants (CGRP antagonists)

  • Mechanism: Block calcitonin gene-related peptide receptors 5
  • Examples: Ubrogepant, rimegepant 1
  • Side Effects: Nausea, somnolence 5
  • Advantage: No vascular contraindications like triptans 5

• Ditans (5-HT1F agonists)

  • Mechanism: Selective 5-HT1F receptor agonism without vasoconstrictive effects 1
  • Example: Lasmiditan 1
  • Side Effects: Dizziness, somnolence, paresthesia, driving impairment 1

Preventive Treatment Classes

First-Line Preventive Agents

Beta Blockers

• Mechanism of Action: Block beta-adrenergic receptors, possibly affecting serotonergic transmission 1
• Examples: Propranolol, timolol 1
• Typical Dosing:
  • Propranolol: 80-240mg/day 1
  • Timolol: 20-30mg/day 1
• Side Effects: Fatigue, bradycardia, hypotension, depression, sleep disturbances 1

Antidepressants

• Mechanism of Action: Increase synaptic serotonin and norepinephrine 1
• Examples: Amitriptyline (tricyclic) 1
• Typical Dosing: 30-150mg/day 1
• Side Effects: Sedation, dry mouth, constipation, weight gain, orthostatic hypotension 1

Anticonvulsants

• Mechanism of Action: Enhance GABA activity, block sodium channels, inhibit glutamate release 1
• Examples: Divalproex sodium, sodium valproate 1
• Typical Dosing:
  • Divalproex sodium: 500-1500mg/day 1
  • Sodium valproate: 800-1500mg/day 1
• Side Effects: Nausea, tremor, weight gain, hair loss, hepatotoxicity, teratogenicity 1

Other Preventive Options

Calcium Channel Blockers

• Mechanism of Action: Block calcium influx, affecting neurovascular function 1
• Example: Flunarizine (not available in US) 1
• Side Effects: Sedation, weight gain, depression, extrapyramidal symptoms 1

Nutraceuticals

• Examples: Magnesium, riboflavin (vitamin B2), feverfew 1
• Mechanism: Various - magnesium affects neurotransmission and vasoconstriction; riboflavin improves mitochondrial function 1
• Evidence: Fair evidence for modest efficacy 1

Key Clinical Considerations

• Route of Administration: Consider non-oral routes when nausea/vomiting are prominent symptoms 1
• Medication Overuse: Limit acute treatments to no more than twice weekly to prevent medication overuse headache 1
• Preventive Therapy Indications: Consider when attacks occur ≥2 times monthly with ≥3 days disability, when acute treatments fail or are contraindicated, when abortive medications are used >twice weekly, or with uncommon migraine variants 1
• Treatment Strategy: Use a stepped care approach, starting with NSAIDs for mild-moderate attacks and triptans for moderate-severe attacks 1, 5
• Timing of Treatment: Triptans are most effective when taken early in an attack while pain is still mild, but should not be taken during aura phase 1

Common Pitfalls to Avoid

• Using acetaminophen alone, which lacks evidence for efficacy in migraine 1
• Failing to treat associated symptoms like nausea, which significantly contributes to migraine disability 1
• Not considering medication overuse headache when patients use acute treatments frequently 1
• Using triptans in patients with cardiovascular contraindications 1, 3
• Not trying a different triptan when one fails (response may vary between different triptans) 1
• Using opioids or butalbital-containing medications as first-line treatment 5