What are the recommended rescue medications and preventative therapies for a patient with migraine headaches?

Migraine Headache Cheat Sheet: Rescue Medications and Preventatives

RESCUE MEDICATIONS (Acute Treatment)

First-Line: Mild to Moderate Attacks

Start with NSAIDs as your first-line treatment for mild to moderate migraine attacks. 1, 2

• Ibuprofen 400-800 mg at onset 2
• Naproxen sodium 500-825 mg at onset (can repeat every 2-6 hours, max 1.5g/day) 2
• Aspirin 1000 mg 1, 2
• Acetaminophen + Aspirin + Caffeine combination 1, 2
• Ketorolac 30-60 mg IM/IV (for severe attacks in urgent care/ED settings) 2

Critical frequency limit: Use acute medications no more than 2 days per week to prevent medication-overuse headache 2, 3

First-Line: Moderate to Severe Attacks

Use triptans for moderate to severe attacks or when NSAIDs fail. 1, 2

Oral Triptans (fastest to slowest onset):

• Rizatriptan 10 mg (fastest oral triptan, peak at 60-90 minutes) 2, 4
• Sumatriptan 50-100 mg 1, 2, 5
• Eletriptan 40 mg 2
• Zolmitriptan 2.5-5 mg 1, 2
• Naratriptan (longest half-life, may decrease recurrence) 2

Non-Oral Triptans (for rapid onset or significant nausea/vomiting):

• Subcutaneous sumatriptan 6 mg (highest efficacy: 59-70% pain-free at 2 hours, onset within 15 minutes) 2, 6
• Intranasal sumatriptan 5-20 mg 2

Triptan contraindications: Uncontrolled hypertension, ischemic heart disease, previous MI, basilar or hemiplegic migraine, significant cardiovascular disease 1, 2, 6

Pro tip: If one triptan fails after 2-3 attempts, try a different triptan—failure of one does not predict failure of others 2

Combination Therapy (Superior to Monotherapy)

For moderate to severe attacks, combine triptan + NSAID for superior efficacy. 2

• Sumatriptan 50-100 mg + Naproxen sodium 500 mg (130 more patients per 1000 achieve sustained relief vs. monotherapy) 2

Antiemetics (Dual Purpose: Nausea + Analgesia)

Add antiemetics for nausea AND direct migraine pain relief through dopamine antagonism. 2

• Metoclopramide 10 mg IV/PO (provides synergistic analgesia, not just antiemetic effect) 1, 2
• Prochlorperazine 10 mg IV/25 mg PO (comparable efficacy to metoclopramide) 2
• Promethazine (rectal suppository or IV when oral route not feasible) 2

Caution: Limit to twice weekly to prevent medication-overuse headache 2

IV "Migraine Cocktail" for Severe Attacks (ED/Urgent Care)

The most effective urgent care cocktail is metoclopramide + ketorolac, NOT prednisone. 2

• Metoclopramide 10 mg IV + Ketorolac 30 mg IV (first-line combination) 2
• Alternative: Prochlorperazine 10 mg IV + Ketorolac 30 mg IV 2

Second-Line/Alternative Agents

• Dihydroergotamine (DHE) intranasal or IV (good efficacy, avoid with triptans within 24 hours) 1, 2
• Ubrogepant 50-100 mg or Rimegepant (CGRP antagonists—safe with cardiovascular disease) 2
• Lasmiditan 50-200 mg (no vasoconstriction, but causes dizziness—no driving for 8 hours) 2

Rescue/Last Resort (Use Sparingly)

Reserve opioids only when other treatments fail, contraindicated, or abuse risk addressed. 1, 2

• Butorphanol nasal spray (best evidence among opioids) 1
• Opioids or butalbital compounds (avoid routinely—cause dependency, rebound headaches, loss of efficacy) 1, 2, 3

Corticosteroids (For Recurrence Prevention)

• Dexamethasone or prednisone (reduces headache recurrence after ED discharge, NOT for acute pain relief) 2, 7

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PREVENTATIVE MEDICATIONS

Indications for Starting Prevention

Initiate preventive therapy if any of the following apply: 1, 8

• ≥2 migraine attacks per month causing disability for ≥3 days
• Using acute medications >2 days per week
• Failure of or contraindications to acute treatments
• Uncommon migraine conditions (hemiplegic, prolonged aura, migrainous infarction)

First-Line Preventatives (Start Here)

Choose based on comorbidities and patient-specific factors. 1, 8

Beta-Blockers (Best Evidence):

• Propranolol 80-240 mg/day 1, 8
• Timolol 20-30 mg/day 1, 8
• Alternatives: Atenolol, bisoprolol, metoprolol 8

Best for: Patients with hypertension, anxiety 8

Antiepileptics:

• Topiramate 50-100 mg/day (causes weight loss—ideal for obesity) 8
• Divalproex sodium 500-1500 mg/day or Sodium valproate 800-1500 mg/day 1, 8

CRITICAL: Valproate is strictly contraindicated in women of childbearing potential due to teratogenic effects 8

Antihypertensives:

• Candesartan (ideal for comorbid hypertension) 8

Second-Line Preventatives

• Amitriptyline 30-150 mg/day (best for comorbid depression, anxiety, or mixed migraine/tension-type headache) 1, 8
• Flunarizine 5-10 mg/day at night (effective but not available in US; avoid in elderly due to depression/extrapyramidal symptoms) 9, 8

Third-Line: CGRP Monoclonal Antibodies

Use when 2-3 oral preventives have failed or are contraindicated. 8

• Erenumab, Fremanezumab, or Galcanezumab (monthly subcutaneous injection) 8
• Eptinezumab (IV quarterly) 8

Trial period: Assess efficacy only after 3-6 months 8
Cost: $5,000-$6,000 annually 8

Fourth-Line: For Chronic Migraine Only

• OnabotulinumtoxinA (chronic migraine only, NOT episodic; assess after 6-9 months) 8

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, biofeedback, relaxation training 8
• Neuromodulatory devices 8
• Acupuncture (not superior to sham but may help) 8
• Riboflavin (Vitamin B2) 10

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CRITICAL PITFALLS TO AVOID

Medication-Overuse Headache (MOH): Using acute medications >2 days/week causes rebound headaches and daily headaches—transition to preventive therapy immediately 2, 3

Recurrence: 40% of patients experience headache recurrence within 24 hours after initial triptan response—treat with second dose or consider preventive therapy 4, 5

Triptan failure: Don't abandon triptans after one failure—try different triptans, different routes (subcutaneous), or add NSAID 2

Pregnancy: Acetaminophen is safest; sumatriptan may be option for selected patients; avoid valproate entirely 8, 11

Preventive trial duration: Allow 2-3 months for oral agents, 3-6 months for CGRP antibodies, 6-9 months for Botox before declaring failure 8