Breakthrough Migraine Medications
For acute treatment of breakthrough migraine attacks in adults, use triptans combined with NSAIDs (e.g., sumatriptan + naproxen) as first-line therapy; if this fails or is not tolerated, escalate to CGRP antagonists (gepants: rimegepant, ubrogepant, zavegepant) or lasmiditan as third-line options. 1, 2
First-Line Acute Treatment Options
NSAIDs and Acetaminophen
- Ibuprofen 400–800 mg, naproxen 500–1000 mg, or aspirin 1000 mg should be initiated as monotherapy for moderate-to-severe episodic migraine in patients who have not previously used simple analgesics. 1, 2
- Acetaminophen 1000 mg is an acceptable alternative when NSAIDs are contraindicated. 1, 2
- Ensure adequate dosing before deeming treatment a failure. 2
Combination Therapy (Triptan + NSAID)
- Adding a triptan to an NSAID (most studied: sumatriptan + naproxen) yields approximately 180 additional sustained pain-relief events per 1000 patients at 48 hours compared with NSAID monotherapy. 2
- This combination reduces rescue-medication use by approximately 160 events per 1000 patients versus monotherapy. 2
- Begin treatment as soon as possible after migraine onset to maximize pain freedom and sustained relief. 1, 2
Second-Line: Triptan Selection
Available Oral Triptans
- Choose among almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, or zolmitriptan based on patient preference for route, cost, and side-effect profile. 2
- Patients who do not respond to one triptan may achieve relief with another triptan within the same class. 2
Non-Oral Formulations
- For patients with severe nausea or vomiting, consider non-oral triptan formulations (nasal spray, injectable) combined with an antiemetic such as metoclopramide or prochlorperazine. 1, 2
Third-Line: CGRP Antagonists (Gepants)
Specific Agents
- Rimegepant, ubrogepant, or zavegepant are recommended for patients who cannot tolerate or have failed triptan + NSAID/acetaminophen combinations. 1, 2
- These agents have a lower likelihood of pain freedom and relief at 2 hours compared with triptan + NSAID combination therapy (low-certainty evidence). 1
Cost Considerations
- CGRP antagonists are substantially more expensive, with annualized costs of approximately $4,959–$5,994 USD for oral formulations and $8,800 USD for intranasal spray formulations, compared with triptan combinations at approximately $500 USD per year. 1, 2
Fourth-Line: Lasmiditan
- Lasmiditan is reserved for patients who have failed all other acute-treatment options outlined in this guideline. 1, 2
- Evidence for lasmiditan showed insufficient-certainty for comparative effectiveness findings on prioritized health outcomes. 1
Contraindicated Medications
Never Use
- Opioids and butalbital-containing medications must never be used for acute episodic migraine due to risk of dependence, rebound headaches, and loss of therapeutic efficacy. 1, 2
- These agents are especially discouraged in patients with chronic daily headache due to heightened risk of medication-overuse headache. 2
Medication-Overuse Headache Prevention
- Limit the use of any acute analgesic (NSAID, acetaminophen, triptan, or combination product) to fewer than 15 days per month to avoid medication-overuse headache. 1, 2
- The threshold varies by treatment: ≥15 days per month with NSAIDs; ≥10 days per month with triptans. 1
- If acute medication use approaches 15 days per month, intensify preventive strategies promptly. 2
Adjunctive Antiemetic Therapy
- Metoclopramide enhances gastric motility that is often impaired during migraine attacks, facilitating faster drug absorption. 2
- Prochlorperazine (oral or IV) effectively reduces headache intensity and concurrently treats associated nausea. 2
Special Populations
- Discuss potential adverse effects of acute migraine medications with patients of childbearing potential, pregnant, or breastfeeding before initiating therapy. 1, 2
- Most trial data derive from females of reproductive age experiencing 1–8 migraine attacks per month. 2