What is the recommended acute and preventive treatment for migraine without aura?

Treatment for Migraine Without Aura

For acute treatment, start with NSAIDs (ibuprofen 400–800 mg, naproxen 500–825 mg, or aspirin 1000 mg) for mild-to-moderate attacks, and add a triptan (sumatriptan 50–100 mg) for moderate-to-severe attacks or when NSAIDs fail—this combination is superior to either agent alone. 1, 2

Acute Treatment Algorithm

First-Line: Mild-to-Moderate Attacks

• NSAIDs are the recommended initial therapy, with ibuprofen 400–800 mg every 6–8 hours, naproxen 500–825 mg, or aspirin 900–1000 mg as needed. 1, 2
• NSAIDs work by inhibiting cyclooxygenase enzymes, reducing prostaglandin synthesis and inflammation. 2
• Take medication early in the attack while pain is still mild to achieve the best outcomes—approximately 50% of patients become pain-free at 2 hours when treated early versus only 28% when treatment is delayed. 1

Escalation: Moderate-to-Severe Attacks

• Add a triptan to the NSAID regimen when attacks are moderate-to-severe or when NSAIDs alone fail after 2–3 episodes. 1, 2
• The combination of sumatriptan 50–100 mg plus naproxen 500 mg produces 130 additional patients per 1,000 achieving sustained pain relief at 48 hours compared to sumatriptan alone, with a number-needed-to-treat of 3.5. 1
• Triptans activate serotonin receptors, causing cranial vessel constriction and inhibiting vasoactive neuropeptide release. 2
• Alternative oral triptans include rizatriptan 10 mg (fastest oral triptan, reaching peak concentration in 60–90 minutes), eletriptan 40 mg, or zolmitriptan 2.5–5 mg. 1

Route Selection for Nausea/Vomiting

• When significant nausea or vomiting is present, choose non-oral routes: subcutaneous sumatriptan 6 mg (onset within 15 minutes, 59% pain-free at 2 hours) or intranasal sumatriptan 5–20 mg. 1, 2
• Add an antiemetic (metoclopramide 10 mg IV or prochlorperazine 10 mg IV) 20–30 minutes before or with the acute medication to provide synergistic analgesia and improve gastric motility. 1, 2

Third-Line: CGRP Antagonists (Gepants)

• Rimegepant 75 mg or ubrogepant 50–100 mg are recommended only after failure of triptan-NSAID combinations, particularly when triptans are contraindicated due to cardiovascular disease or uncontrolled hypertension. 1, 3
• Gepants have no vasoconstrictor activity, making them safe in patients with cardiovascular contraindications to triptans. 1

Critical Frequency Limitation

Limit all acute migraine medications to no more than 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 acute treatment is needed more than twice weekly, immediately initiate preventive therapy rather than increasing acute medication frequency. 1

Preventive Treatment Indications

Preventive therapy is indicated when: 1, 2, 4

• ≥2 migraine attacks per month produce disability lasting ≥3 days
• Acute medication use exceeds 2 days per week
• Acute treatments fail, are contraindicated, or cause intolerable side effects
• Patient preference for prevention

First-Line Preventive Medications

• Beta-blockers without intrinsic sympathomimetic activity: propranolol 80–240 mg/day or timolol 20–30 mg/day have the strongest evidence. 1, 4, 5
• Topiramate and divalproex sodium 500–1500 mg/day are also first-line options, though valproate is strictly contraindicated in women of childbearing potential due to teratogenic risk. 1, 4, 5
• Amitriptyline 30–150 mg/day is preferred when comorbid depression, anxiety, or mixed migraine/tension-type headache is present. 1, 4, 5

Second-Line: CGRP Monoclonal Antibodies

• When first-line oral preventives fail, escalate to CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab), which require 3–6 months for full efficacy assessment. 1, 6

Preventive Efficacy Timeline

• Oral agents (beta-blockers, topiramate, amitriptyline): 2–3 months 1
• CGRP monoclonal antibodies: 3–6 months 1
• OnabotulinumtoxinA (for chronic migraine): 6–9 months 1

Contraindications and Safety

• Triptans are contraindicated in ischemic heart disease, uncontrolled hypertension, cerebrovascular disease, basilar or hemiplegic migraine. 1, 2
• Absolutely avoid opioids (codeine, hydromorphone, morphine) and butalbital-containing compounds—they provide questionable efficacy, cause medication-overuse headache, lead to dependency, and worsen long-term outcomes. 1
• NSAIDs should be used cautiously in patients with renal impairment, GI bleeding history, or uncontrolled hypertension. 1

Common Pitfalls to Avoid

• Do not abandon triptan therapy after a single failed attempt—failure of one triptan does not predict failure of others; try at least 2–3 different triptans before escalating. 1
• Do not delay treatment until pain is severe—early administration during mild pain dramatically improves outcomes. 1
• Do not allow patients to increase acute medication frequency in response to treatment failure—this creates medication-overuse headache; instead, transition to preventive therapy. 1
• Do not prescribe opioids simply because a patient requests them or reports "nothing else works" without ensuring adequate trials of NSAIDs, triptans, and combination therapy. 1