What is the recommended acute and preventive treatment strategy for an adult with episodic migraine, including medication choices, dosing, and contraindications?

Migraine Treatment: Acute and Preventive Strategies

Acute Treatment Algorithm

For mild-to-moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg; for moderate-to-severe attacks or when NSAIDs fail after 2-3 episodes, escalate to combination therapy with a triptan plus NSAID, which provides superior efficacy compared to either agent alone. 1

First-Line Therapy

• NSAIDs are the recommended initial treatment for mild-to-moderate attacks, with ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg demonstrating high-certainty evidence for efficacy 1, 2
• Acetaminophen 1000 mg is an alternative first-line option when NSAIDs are contraindicated, though it shows lower effectiveness than NSAIDs 1, 2
• The combination of acetaminophen 1000 mg + aspirin 500-1000 mg + caffeine 130 mg achieves pain reduction to mild or none in 59.3% of patients at 2 hours 2

Second-Line: Triptan Monotherapy or Combination Therapy

• Triptans are indicated for moderate-to-severe attacks or when NSAIDs fail after 2-3 episodes 1, 3
• Oral triptans with strong evidence include sumatriptan 50-100 mg, rizatriptan 10 mg, eletriptan 40 mg, naratriptan, and zolmitriptan 2.5-5 mg 1, 2, 3
• Rizatriptan 10 mg reaches peak concentration in 60-90 minutes, making it the fastest oral triptan 2
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief at 2 hours) with onset within 15 minutes, particularly useful for rapid progression or significant nausea 2, 3
• Intranasal sumatriptan 5-20 mg or other nasal spray triptans are preferred when significant nausea or vomiting is present 2

Combination Therapy: The Strongest Recommendation

The combination of a triptan (sumatriptan 50-100 mg or rizatriptan 10 mg) plus an NSAID (naproxen 500 mg) is superior to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours and 90 more achieving pain relief at 2 hours. 1, 2

• This combination has a number-needed-to-treat of 3.5 for headache relief at 2 hours 2
• The combination of triptan plus acetaminophen is also effective, with 300 more events per 1000 achieving pain freedom at 2 hours compared to acetaminophen alone 1
• Treating early (when pain is mild) results in markedly better outcomes: approximately 50% become pain-free at 2 hours versus 28% when treatment is delayed 2

Third-Line: CGRP Antagonists (Gepants) and Ditans

• Ubrogepant 50-100 mg or rimegepant are recommended only after failure of triptan-NSAID combinations 1, 2
• Lasmiditan 50-200 mg (5-HT1F receptor agonist) is an alternative for patients with cardiovascular contraindications to triptans, but patients must not drive or operate machinery for at least 8 hours due to CNS effects 2
• These agents have no vasoconstriction, making them safe for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease 2

Alternative Routes and Rescue Therapy

• Intravenous metoclopramide 10 mg provides direct analgesic effects through central dopamine receptor antagonism and is effective for moderate-to-severe migraine with nausea 1, 2
• Intravenous ketorolac 30 mg has rapid onset with approximately 6 hours duration and minimal rebound headache risk 2
• The combination of IV metoclopramide 10 mg plus IV ketorolac 30 mg is recommended as first-line IV therapy for severe attacks requiring emergency treatment 2
• Dihydroergotamine (DHE) 0.5-1.0 mg IV or intranasal has good evidence for efficacy as monotherapy 1, 2, 3
• Prochlorperazine 10 mg IV is comparable to metoclopramide in efficacy for headache relief 2

Critical Medication-Overuse Prevention

All acute migraine medications—including NSAIDs, triptans, gepants, ditans, and combination analgesics—must be limited to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 2

• If a patient requires acute treatment more than twice weekly, immediately initiate preventive therapy rather than increasing acute medication frequency 1, 2
• Medication-overuse headache occurs with NSAIDs/acetaminophen on ≥15 days/month or triptans/combination analgesics on ≥10 days/month 2

Contraindications and Medications to Avoid

Triptan Contraindications

• Triptans are contraindicated in patients with ischemic heart disease, previous myocardial infarction, coronary artery vasospasm, uncontrolled hypertension, cerebrovascular disease, history of stroke or TIA, or basilar/hemiplegic migraine 2
• Do not use triptans and DHE within 24 hours of each other due to additive vasoconstrictive effects 2

Absolutely Contraindicated Medications

Opioids (hydrocodone, oxycodone, morphine, codeine, tramadol) and butalbital-containing compounds are absolutely contraindicated for migraine treatment because they provide questionable efficacy, carry high risk of dependence, precipitate rebound headaches, and worsen overall migraine outcomes. 1, 2, 3

• If an opioid must be used (only when all other evidence-based treatments are contraindicated, sedation is acceptable, and abuse risk has been addressed), butorphanol nasal spray has better evidence than other opioids 2

---

Preventive Therapy

Indications for Preventive Therapy

Preventive therapy is indicated when a patient experiences ≥2 migraine attacks per month with disability lasting ≥3 days, uses acute medication >2 days per week, has contraindications to or failure of acute treatments, or has uncommon migraine subtypes. 2

• Additional factors include significant adverse events from acute therapies, strong patient preference for prevention, and cost considerations 2

First-Line Preventive Medications

• Beta-blockers without intrinsic sympathomimetic activity are first-line oral preventives with strong evidence 2

  • Propranolol 80-240 mg/day is FDA-approved with strong randomized trial data 2
  • Timolol 20-30 mg/day also has strong evidence 2
  • Metoprolol, atenolol, and nadolol have moderate-quality evidence 2

• Topiramate has proven efficacy in randomized controlled trials for chronic migraine 2

• Amitriptyline 30-150 mg/day is preferred when patients have comorbid depression, anxiety, or sleep disturbances and is superior for mixed migraine plus tension-type headache 2

Second-Line Preventive Medications

• Sodium valproate (800-1500 mg/day) or divalproex sodium (500-1500 mg/day) should be strictly avoided in women of child-bearing potential due to teratogenic risk 2

Third-Line: CGRP Monoclonal Antibodies and OnabotulinumtoxinA

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) are recommended when oral preventives have failed or are contraindicated 2
• Erenumab (Aimovig) is dosed at 70 mg subcutaneously once monthly, with some patients benefiting from 140 mg monthly 4
• OnabotulinumtoxinA (Botox) is the only FDA-approved preventive therapy specifically for chronic migraine (≥15 headache days per month) and should be used as first-line when three oral preventives have failed 2
  • Recommended dose: 155-195 units injected across 31-39 sites every 12 weeks 2
  • Efficacy should be evaluated after 6-9 months of treatment 2

Timeline for Preventive Efficacy

• Oral agents (beta-blockers, topiramate, amitriptyline): 2-3 months 2
• CGRP monoclonal antibodies: 3-6 months 2
• OnabotulinumtoxinA: 6-9 months 2

---

Special Populations and Situations

Pregnancy and Lactation

• Acetaminophen 1000 mg is the safest first-line option during pregnancy 2
• Valproate is strictly contraindicated during pregnancy due to teratogenic risk 2
• Discuss adverse effects of pharmacologic treatments during pregnancy and lactation before initiating therapy 2

Chronic Migraine (≥15 headache days per month)

• OnabotulinumtoxinA is first-line when three oral preventives have failed 2
• Topiramate is the only oral preventive with proven efficacy in randomized controlled trials for chronic migraine 2
• Eliminate or avoid medication overuse, as it perpetuates chronic migraine 2

Status Migrainosus (>72 hours continuous migraine)

• Corticosteroids (e.g., dexamethasone or methylprednisolone dose pack) may be added to terminate the prolonged attack 2, 5
• Greater occipital nerve block with 1-2% lidocaine can provide adjunctive relief 2
• Intravenous DHE has good evidence for efficacy 2
• Initiate or optimize preventive therapy immediately during or after resolution 2

Pediatric Patients (Age 6-17 Years)

• Ibuprofen (weight-based dosing) is the recommended first-line acute medication 2
• Sumatriptan ODT is approved for adolescents aged 12-17 years for moderate-to-severe attacks 2
• Intranasal sumatriptan and zolmitriptan are the most effective triptan formulations for adolescents 2
• Rizatriptan dosing: 5 mg for patients <40 kg (88 lb), 10 mg for patients ≥40 kg 5
• Limit triptan use to ≤2 days per week to avoid medication-overuse headache 2

Patients on Propranolol

• In adults taking propranolol, only the 5 mg dose of rizatriptan is recommended, up to a maximum of 3 doses in 24 hours (15 mg total) 5
• For pediatric patients ≥40 kg taking propranolol, only a single 5 mg dose of rizatriptan is recommended (maximum 5 mg in 24 hours) 5
• Rizatriptan should not be prescribed to propranolol-treated pediatric patients who weigh <40 kg 5

Cardiovascular Disease or Uncontrolled Hypertension

• Acetaminophen 1000 mg is the safest first-line analgesic when hypertension is uncontrolled 2
• NSAIDs are contraindicated in uncontrolled hypertension as they can further elevate blood pressure 2
• Gepants (ubrogepant, rimegepant) or lasmiditan are safe alternatives to triptans for patients with cardiovascular contraindications 2

---

Common Pitfalls and How to Avoid Them

• Do not abandon triptan therapy after a single failed attempt—if one triptan is ineffective, try a different triptan, as failure of one does not predict failure of others 2, 6
• Do not allow patients to increase frequency of acute medication use in response to treatment failure; instead, transition to preventive therapy 2
• Do not prescribe opioids or butalbital compounds simply because a patient requests them or reports "nothing else has worked" without first ensuring adequate trials of NSAIDs, triptans, and combination therapy 2
• Do not delay preventive therapy while trialing multiple acute strategies; this undermines timely control of migraine 2
• Do not use ketamine for short-term treatment of migraine attacks, as it lacks proven efficacy and carries safety concerns 2
• Avoid routine neuroimaging for typical recurrent migraine without red flags (thunderclap onset, progressive worsening, fever, focal neurological deficits, new-onset after age 50) to avoid unnecessary radiation, cost, and incidental findings 2

---

Dosing Summary Table

Medication	Dose	Maximum Frequency
Ibuprofen	400-800 mg	≤2 days/week
Naproxen sodium	500-825 mg	≤2 days/week
Aspirin	1000 mg	≤2 days/week
Acetaminophen	1000 mg	≤2 days/week
Sumatriptan (oral)	50-100 mg	≤2 days/week; max 200 mg/24h
Sumatriptan (subcutaneous)	6 mg	≤2 days/week; max 12 mg/24h
Sumatriptan (intranasal)	5-20 mg	≤2 days/week
Rizatriptan	5-10 mg	≤2 days/week; max 30 mg/24h [5]
Rizatriptan (with propranolol)	5 mg only	Max 15 mg/24h (adults) [5]
Eletriptan	40 mg	≤2 days/week
Zolmitriptan	2.5-5 mg	≤2 days/week
Ubrogepant	50-100 mg	Max 8 attacks/30 days
Lasmiditan	50-200 mg	≤2 days/week; no driving ×8h
Metoclopramide (IV)	10 mg	≤2 days/week
Ketorolac (IV)	30 mg	≤2 days/week
Prochlorperazine (IV)	10 mg	≤2 days/week
DHE (IV)	0.5-1.0 mg	Max 2 mg/day

1, 2, 5, 4, 3, 7