What medications are used to terminate an acute attack of migraine?

Acute Migraine Treatment

For mild to moderate migraine attacks, start with NSAIDs (aspirin, ibuprofen, naproxen sodium, or the combination of acetaminophen + aspirin + caffeine) as first-line therapy; for moderate to severe attacks or when NSAIDs fail, use triptans as first-line therapy. 1, 2, 3

Treatment Algorithm by Attack Severity

Mild to Moderate Migraine

• Begin with NSAIDs immediately at attack onset when pain is still mild to maximize efficacy 1, 3
• Specific NSAIDs with strong evidence: aspirin, ibuprofen, naproxen sodium 1, 2
• Combination therapy (acetaminophen + aspirin + caffeine) is recommended when patients respond poorly to single-agent NSAIDs 1, 2
• Naproxen dosing: 500-825 mg initially, can repeat every 2-6 hours (maximum 1.5 g/day) 1
• If inadequate response within 2 hours, escalate to a triptan 2

Moderate to Severe Migraine

• Triptans are first-line therapy for moderate to severe attacks 1, 2, 3
• Oral triptans with strong evidence: sumatriptan, rizatriptan, naratriptan, zolmitriptan 1, 2
• Oral sumatriptan 100 mg provides pain-free response in 28% at 2 hours (NNT 6.1) compared to 11% with placebo 4
• Subcutaneous sumatriptan 6 mg is the most effective route, providing pain-free response in 59% at 2 hours (NNT 2.3), with fastest onset of action 1, 5
• Intranasal sumatriptan (5-20 mg) provides significant pain relief as early as 15 minutes post-administration 1, 6

Attacks with Significant Nausea or Vomiting

• Select non-oral routes of administration: subcutaneous or intranasal formulations 1, 2
• Add antiemetics even if vomiting is not present, as nausea itself is disabling 1, 2
• Metoclopramide 10 mg IV provides synergistic analgesia beyond treating nausea alone 1
• Prochlorperazine 10 mg IV is comparable to metoclopramide in efficacy 1

Combination and Adjunctive Strategies

When Single-Agent Therapy Fails

• Combine a triptan with an NSAID for superior efficacy in patients with inadequate relief from monotherapy 3
• If one triptan fails, try a different triptan before abandoning the class, as failure of one does not predict failure of others 1, 3
• Adding an antiemetic (metoclopramide 10 mg or prochlorperazine 25 mg) 20-30 minutes before NSAID provides synergistic analgesia 1

Parenteral Options for Severe Attacks

• IV metoclopramide 10 mg plus IV ketorolac 30 mg is first-line combination therapy for severe migraine requiring intravenous treatment 1
• Ketorolac has rapid onset with 6-hour duration and minimal rebound headache risk 1
• Intranasal dihydroergotamine (DHE) has good evidence for efficacy and safety as monotherapy 1, 2

Third-Line Options for Refractory Migraine

• Ditans (lasmiditan) for patients not responding to triptans, though may cause driving impairment 3
• Gepants (rimegepant, ubrogepant) as CGRP antagonists for patients who cannot tolerate triptans 3

Critical Medication-Overuse Headache Prevention

• Limit acute therapy to no more than twice weekly to prevent medication-overuse headache 1, 3
• Frequent use (more than twice weekly) leads to increasing headache frequency and potentially daily headaches 1
• If requiring acute treatment more than 2 days per week, initiate preventive therapy rather than increasing acute medication frequency 1

Medications to Avoid

• Acetaminophen alone lacks evidence for efficacy in migraine treatment 2
• Opioids should be reserved only when other medications cannot be used, sedation is not a concern, and abuse risk has been addressed 1
• Opioids lead to dependency, rebound headaches, and eventual loss of efficacy 1

Route-Specific Considerations

• Subcutaneous administration provides most rapid and complete pain relief but with higher adverse event rates 5
• Oral disintegrating tablets (rizatriptan, zolmitriptan) and intranasal sprays allow treatment without liquids, useful for patients with nausea or difficulty swallowing 6
• Intranasal sprays are absorbed rapidly with prompt onset, allowing significant pain-free rates as early as 15 minutes 6

Dosing Adjustments for Special Populations

• Hepatic impairment: Start almotriptan at 6.25 mg, maximum 12.5 mg per 24 hours 7
• Severe renal impairment: Start almotriptan at 6.25 mg, maximum 12.5 mg per 24 hours 7
• Adolescents age 12-17 years: Almotriptan 6.25-12.5 mg is effective for headache pain 7

Key Pitfalls to Avoid

• Do not wait until pain is moderate or severe to treat; early administration when pain is mild improves efficacy 1, 3
• Do not allow patients to increase frequency of acute medication in response to treatment failure; this creates medication-overuse headache 1
• Do not use triptans in patients with ischemic heart disease, cerebrovascular disease, peripheral vascular disease, or uncontrolled hypertension 7
• Maximum daily dose of sumatriptan should not exceed 200 mg oral or 12 mg subcutaneous 5