What are the treatment options for persistent migraine headaches?

Treatment of Persistent Migraine Headaches

Start with combination therapy of a triptan plus an NSAID or acetaminophen as first-line treatment for persistent moderate to severe migraines, initiating treatment as early as possible after headache onset. 1

Acute Treatment Algorithm

First-Line Therapy

For mild to moderate attacks:

• Begin with NSAIDs alone: aspirin, ibuprofen, naproxen sodium, or diclofenac potassium 1
• Acetaminophen can be used but has lower efficacy and should only be chosen if NSAIDs are contraindicated 2

For moderate to severe attacks:

• Use combination therapy with a triptan (sumatriptan, rizatriptan, naratriptan, or zolmitriptan) plus an NSAID or acetaminophen 1
• This combination approach provides superior efficacy compared to monotherapy 1
• Triptans demonstrate headache response rates of 52-62% at 2 hours and 65-79% at 4 hours, compared to 17-27% with placebo 3

Second-Line Options (When First-Line Fails)

If combination triptan-NSAID therapy is inadequate or not tolerated:

• CGRP antagonists-gepants: rimegepant, ubrogepant, or zavegepant 1
• Ergot alkaloid: dihydroergotamine (particularly intranasal formulation) 1, 2

Third-Line Option

• Lasmiditan (a ditan) should be reserved for patients who fail all other treatments in this guideline 1

Adjunctive Therapy for Nausea/Vomiting

• Add non-oral triptans with antiemetics (such as metoclopramide or domperidone) for patients experiencing severe nausea or vomiting 1, 4

Critical Medications to AVOID

Never use opioids or butalbital-containing medications for persistent migraine treatment due to questionable efficacy, significant adverse effects, dependency risk, and potential for medication overuse headache 1, 2

Medication Overuse Headache Prevention

Be vigilant about frequency of acute medication use:

• NSAIDs: limit to <15 days per month 1
• Triptans: limit to <10 days per month 1
• Medication overuse headache develops when acute medications are used on ≥15 days per month for ≥3 months, presenting as daily or near-daily headaches 1
• If overuse is occurring, abrupt withdrawal is preferred (except for opioids), combined with patient education 1

When to Add Preventive Therapy

Consider initiating preventive medications when:

• Migraines occur frequently (≥2 days per month) 4
• Acute treatment provides inadequate response despite optimization 1
• Patient is at risk for medication overuse headache 1

Evidence-based preventive options for chronic migraine include:

• Topiramate (first choice due to lower cost) 1
• OnabotulinumtoxinA 1
• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) - typically reserved for patients who have failed 2-3 other preventive medications 1

Essential Lifestyle Modifications

Counsel all patients on these evidence-based modifications:

• Maintain adequate hydration and regular meal schedule 1, 2
• Ensure sufficient and consistent sleep (7-9 hours nightly) 1
• Engage in regular moderate to intense aerobic exercise 1
• Practice stress management through relaxation techniques or mindfulness 1
• Pursue weight loss if overweight or obese, as obesity is a risk factor for chronic migraine transformation 1
• Identify and modify personal migraine triggers through detailed history-taking 1

Special Populations

For pregnant or breastfeeding women:

• Discuss adverse effects of all pharmacologic treatments during pregnancy and lactation before prescribing 1
• Acetaminophen is the safest option during pregnancy 5
• Sumatriptan may be considered in selected pregnant patients and is compatible with breastfeeding 5

Cost Considerations

• Prescribe less costly recommended medications when equally effective 1
• Generic NSAIDs and triptans are significantly less expensive than newer CGRP antagonists (annualized costs: gepants $4,959-$8,800 vs. generic triptans/NSAIDs <$500) 1

Common Pitfalls to Avoid

• Do not delay treatment - early initiation maximizes efficacy 1, 2
• Do not use triptan monotherapy when combination therapy is appropriate - adding an NSAID or acetaminophen improves outcomes 1
• Do not continue ineffective treatments - if a medication fails after adequate trial, switch within or between classes 6
• Do not overlook comorbidities - depression, anxiety, sleep disturbances, and chronic pain conditions are common and influence treatment selection 1