Severe Migraine Medical Management
For severe migraine, initiate combination therapy with a triptan (sumatriptan 50–100 mg) plus an NSAID (naproxen 500 mg) as first-line treatment for moderate-to-severe attacks, and immediately start preventive therapy if attacks occur more than twice weekly to prevent medication-overuse headache and progression to chronic migraine. 1
Acute Treatment Algorithm
First-Line Therapy for Severe Attacks
Combination therapy with sumatriptan 50–100 mg PLUS naproxen sodium 500 mg provides superior efficacy compared to either agent alone, achieving sustained pain relief in 130 additional patients per 1,000 at 48 hours. 1
Administer medication as early as possible during the attack while pain is still mild—early treatment results in approximately 50% pain-free response at 2 hours versus only 28% when delayed until pain is moderate or severe. 1
For patients with significant nausea or vomiting preventing oral intake, subcutaneous sumatriptan 6 mg provides the highest efficacy with onset within 15 minutes, achieving complete pain relief in approximately 59% of patients by 2 hours. 1
Second-Line Parenteral Options
Intravenous metoclopramide 10 mg plus ketorolac 30 mg is the recommended IV combination for severe migraine requiring emergency treatment, providing both direct analgesic effects and rapid pain relief with minimal rebound headache risk. 1
Dihydroergotamine (DHE) 0.5–1.0 mg IV has good evidence for efficacy as monotherapy when NSAIDs are contraindicated, with a maximum of 2 mg IV per day. 1
Third-Line Options When Triptans Fail
If one triptan fails after 2–3 headache episodes, try a different triptan—failure of one does not predict failure of others; alternatives include rizatriptan 10 mg (fastest oral triptan, peak at 60–90 minutes), eletriptan 40 mg, or zolmitriptan 2.5–5 mg. 1
CGRP antagonists (ubrogepant 50–100 mg or rimegepant) are recommended as third-line options for patients who do not tolerate or have inadequate response to triptan-NSAID combinations. 1
Assessment of Aura
Diagnostic Criteria
Suspect migraine with aura when visual, sensory, or speech disturbances develop gradually over ≥5 minutes, last 5–60 minutes, and are followed by headache within 60 minutes. 2
Visual aura occurs in over 90% of patients with aura and typically includes positive phenomena (scintillations, zigzag lines) followed by negative phenomena (scotoma). 3
Differentiate aura from TIA: aura symptoms spread gradually and occur in succession (visual → sensory → aphasic), whereas TIA symptoms have sudden, simultaneous onset corresponding to a vascular territory. 2, 3
Red Flags Requiring Urgent Neuroimaging
Order MRI immediately for: thunderclap headache, atypical aura, recent head trauma, impaired memory or consciousness, progressive worsening, fever with neck stiffness, or any new focal neurological deficit. 2, 1
Long-duration aura (>1 hour), late-onset aura, or dramatic increase in aura frequency warrant urgent evaluation to exclude secondary causes. 3
Frequency Assessment and Preventive Therapy Indications
When to Initiate Prevention
Start preventive therapy immediately if the patient experiences ≥2 migraine attacks per month causing disability lasting ≥3 days, or requires acute medication use more than 2 days per week. 2, 1
Chronic migraine (≥15 headache days per month for >3 months with migraine features on ≥8 days) mandates aggressive preventive therapy to prevent progression and medication-overuse headache. 2
First-Line Preventive Medications
Beta-blockers without intrinsic sympathomimetic activity: propranolol 80–240 mg/day or timolol 20–30 mg/day have strong randomized trial evidence for migraine prevention. 1
Topiramate (dose titrated to therapeutic level) and amitriptyline 30–150 mg/day (especially for comorbid depression, anxiety, or mixed migraine/tension-type headache) are alternative first-line options. 2, 1
Third-Line Options for Refractory Cases
- CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) or onabotulinumtoxinA 155–195 U every 12 weeks are recommended when oral preventives fail, with efficacy assessed after 3–6 months for CGRP antibodies and 6–9 months for Botox. 1
Management of Comorbidities
Hypertension
Triptans remain safe in controlled hypertension but are contraindicated in uncontrolled hypertension, ischemic heart disease, previous MI, coronary vasospasm, cerebrovascular disease, or history of stroke/TIA. 1
Beta-blockers (propranolol, metoprolol) serve dual purposes as both migraine preventives and antihypertensives, making them ideal first-line preventive agents in hypertensive patients. 1
Candesartan 16–32 mg daily offers effective migraine prevention with good tolerability, particularly beneficial when hypertension coexists. 4
Depression
Amitriptyline 30–150 mg/day is the preferred preventive medication when depression, anxiety, or sleep disturbances coexist with migraine, providing dual benefit for both conditions. 1
Avoid valproate/divalproex in women of childbearing potential due to teratogenic risk. 1
Cardiovascular Disease
Migraine with aura is associated with increased risk of ischemic stroke, atrial fibrillation, myocardial infarction, and cardiovascular mortality—heightened vigilance for modifiable cardiovascular risk factors is mandatory. 5, 6, 7, 8
Triptans are absolutely contraindicated in patients with ischemic vascular disease, vasospastic coronary disease, or significant cardiovascular disease. 1
CGRP antagonists (gepants) or ditans (lasmiditan) have no vasoconstriction, making them safe alternatives for patients with cardiovascular contraindications to triptans. 1
Acetaminophen 1000 mg is the safest analgesic when cardiovascular disease or uncontrolled hypertension precludes NSAID use. 1
Critical Medication-Overuse Prevention
Frequency Limits
Limit ALL acute migraine medications to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 2, 1
NSAIDs and acetaminophen trigger medication-overuse headache at ≥15 days/month; triptans, ergots, and combination analgesics at ≥10 days/month. 2, 1
Management of Established Medication-Overuse Headache
Abrupt cessation of overused medication is recommended—evidence does not support gradual taper; warn patients of temporary worsening (2–10 days) during withdrawal. 1
Initiate preventive therapy immediately during withdrawal rather than substituting another acute medication, which merely transfers the overuse. 1
Medications to Absolutely Avoid
Opioids (hydrocodone, oxycodone, morphine, codeine, tramadol) are absolutely contraindicated for migraine treatment due to questionable efficacy, high dependence risk, rebound headaches, and worse long-term outcomes. 1
Butalbital-containing compounds should never be prescribed due to high medication-overuse headache risk, dependency potential, and lack of proven efficacy compared to safer alternatives. 1, 4
Special Populations
Older Adults
NSAIDs (ibuprofen 400–800 mg, naproxen 500–825 mg) remain first-line but require careful monitoring for gastrointestinal and cardiovascular risks in elderly patients. 4
Acetaminophen is the safest option when NSAIDs are contraindicated, though it should be combined with other agents for optimal efficacy. 4
Triptans are generally not recommended in elderly patients due to higher likelihood of cardiovascular disease, though no robust evidence supports increased cerebrovascular events from triptan use per se. 4
Women of Childbearing Potential
Paracetamol (acetaminophen) is the recommended acute treatment during pregnancy; avoid preventive therapy if possible. 2
Valproate/divalproex is absolutely contraindicated in women of childbearing potential due to teratogenic risk. 1
Combined hormonal contraception with estrogens significantly increases stroke risk in women with migraine with aura—progestin-only methods are preferred. 3
Follow-Up and Treatment Evaluation
Use a headache diary (paper or electronic) to record frequency, severity, associated symptoms, triggers, and acute medication use—this improves diagnostic accuracy and identifies modifiable triggers. 2, 1
Assess treatment response 2–3 months after starting or modifying therapy, evaluating both effectiveness and adverse events. 2
Refer to a headache specialist when diagnosis is uncertain, all treatments have failed, chronic migraine develops, or complications arise. 2, 1