What are the next steps for a patient with migraines who has not responded to sumatriptan (Imitrex)

Next Steps for Migraine Unresponsive to Sumatriptan

Try a different triptan first, as failure of one triptan does not predict failure of others—switching triptans results in 25-81% response rates even in patients with poor sumatriptan response. 1, 2

Immediate Alternative Triptan Options

• Switch to an alternative oral triptan such as rizatriptan, zolmitriptan, naratriptan, or almotriptan, as clinical trials demonstrate that lack of response to sumatriptan does not predict responsiveness to other triptans 1, 2
• Consider combination therapy with triptan + NSAID (such as sumatriptan 50-100 mg plus naproxen sodium 500 mg), which is superior to either agent alone and provides 130 more patients per 1000 achieving sustained pain relief at 48 hours 1
• If oral sumatriptan failed, try subcutaneous sumatriptan 6 mg, which provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes, particularly for patients with rapid progression to peak intensity or significant vomiting 1, 3
• Alternatively, try intranasal sumatriptan 20 mg or intranasal zolmitriptan, which bypass gastric absorption and provide pain relief as early as 15 minutes post-administration 1, 4

Critical Assessment: Rule Out Medication-Overuse Headache

• Assess frequency of acute medication use—if the patient uses acute medications more than 2 days per week (10 days per month for triptans, 15 days per month for NSAIDs), medication-overuse headache (MOH) is likely causing treatment failure 1, 5
• MOH creates a vicious cycle where increasing medication use paradoxically increases headache frequency, potentially leading to daily headaches 1
• Do not allow patients to increase frequency of acute medication use in response to treatment failure—instead transition to preventive therapy while optimizing acute treatment strategy 1

Escalation to Third-Line Agents (If All Triptans Fail)

• CGRP antagonists (gepants) such as ubrogepant 50-100 mg or rimegepant are the primary alternative when triptans fail or are contraindicated, with no vasoconstriction making them safe for patients with cardiovascular disease 1
• Lasmiditan (Reyvow) 50-200 mg, a 5-HT1F receptor agonist without vasoconstrictor activity, is a second-line option when gepants are unavailable or ineffective, though patients must not drive for at least 8 hours after administration due to CNS effects 1

Initiate Preventive Therapy Immediately

• Preventive therapy is indicated if headaches continue to impair quality of life despite optimized acute therapy, or if the patient uses acute medications more than 2 days per week 1, 5
• First-line preventive options include propranolol 80-240 mg/day, topiramate, amitriptyline 30-150 mg/day, or divalproex sodium 1, 5
• Preventive therapy reduces attack frequency and can restore responsiveness to acute treatments, with efficacy requiring 2-3 months for oral agents 1
• CGRP monoclonal antibodies should be considered when oral preventives have failed or are contraindicated, with efficacy assessed after 3-6 months 1

Acute Treatment for Severe Attacks Requiring IV Therapy

• IV metoclopramide 10 mg plus IV ketorolac 30 mg is first-line combination therapy for severe migraine attacks requiring intravenous treatment, providing rapid pain relief while minimizing rebound headache risk 1, 5
• IV prochlorperazine 10 mg is an alternative that effectively relieves headache pain and is comparable to metoclopramide in efficacy 1
• Dihydroergotamine (DHE) intranasal or IV has good evidence for efficacy as monotherapy for acute migraine attacks 1

Critical Pitfalls to Avoid

• Never use opioids or butalbital-containing compounds for acute migraine treatment, as they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 1
• Ensure early administration of triptans, as they are most effective when taken early in the attack while headache is still mild 1
• Strictly limit all acute migraine medications to no more than 2 days per week to prevent medication-overuse headache 1, 5

Timing and Route Optimization

• Taking medication early, when pain is mild, is more effective than waiting until pain is moderate or severe 3
• For patients with rapid progression to peak intensity or significant nausea/vomiting, subcutaneous or intranasal routes provide faster onset than oral formulations 1, 4