What is the recommended acute and preventive treatment plan for a patient with migraine, including medication choices, dosing, contraindications, and non‑pharmacologic measures?

Migraine Management: Acute and Preventive Treatment

Acute Treatment Algorithm

Mild to Moderate Migraine (First-Line)

NSAIDs are the recommended first-line therapy for mild to moderate migraine attacks, with ibuprofen 400–800 mg, naproxen sodium 500–825 mg, or aspirin 900–1000 mg demonstrating the strongest evidence. 1, 2

• Combination therapy with acetaminophen 1000 mg + aspirin 500–1000 mg + caffeine 130 mg achieves pain reduction to mild or none in 59.3% of patients at 2 hours and represents an effective first-line option. 1
• Acetaminophen 1000 mg alone is appropriate for patients with NSAID contraindications, though it demonstrates lower efficacy than NSAIDs. 1
• Limit all acute medications to no more than 2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 2

Moderate to Severe Migraine (Triptan Strategy)

Triptans are first-line therapy for moderate to severe attacks or when NSAIDs fail after 2–3 episodes. 1, 2

• Oral triptans with strong evidence include sumatriptan 50–100 mg, rizatriptan 10 mg (fastest oral triptan, reaching peak concentration in 60–90 minutes), eletriptan 40 mg, and zolmitriptan 2.5–5 mg. 1, 2
• Combination therapy with a triptan plus NSAID (e.g., sumatriptan 50–100 mg + naproxen 500 mg) is superior to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours. 1
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief by 2 hours) with onset within 15 minutes, making it ideal for rapidly progressive attacks or significant nausea/vomiting. 1, 2
• Intranasal sumatriptan 5–20 mg or other nasal spray triptans are particularly useful when significant nausea or vomiting is present. 1, 2
• If one triptan fails after 2–3 headache episodes, try a different triptan before abandoning the class, as failure of one does not predict failure of others. 1

Migraine with Prominent Nausea/Vomiting

Select non-oral routes of administration when nausea is a significant component, and add an antiemetic to specifically target nausea symptoms. 2

• Metoclopramide 10 mg IV provides direct analgesic effects through central dopamine receptor antagonism beyond its antiemetic properties, and should not be restricted only to patients who are vomiting. 1
• Prochlorperazine 10 mg IV effectively relieves headache pain and has been shown to be comparable to metoclopramide in efficacy. 1
• The optimal IV "headache cocktail" for severe migraine is metoclopramide 10 mg IV + ketorolac 30 mg IV, providing rapid pain relief while minimizing side effects and rebound headache risk. 1

Refractory Migraine Strategy (Third-Line)

When triptans and NSAIDs fail, escalate to CGRP antagonists (gepants) or ditans as the primary oral alternatives. 1

• Ubrogepant 50–100 mg or rimegepant are recommended as third-line options for moderate to severe acute episodic migraine in patients who do not tolerate or have inadequate response to triptan-NSAID combinations. 1
• Lasmiditan 50–200 mg (a 5-HT1F receptor agonist without vasoconstrictor activity) is a safe alternative for patients with cardiovascular disease, but patients must not drive or operate machinery for at least 8 hours after taking it due to CNS effects. 1
• Dihydroergotamine (DHE) 0.5–1.0 mg IV or intranasal has good evidence for efficacy as monotherapy when NSAIDs are contraindicated. 1
• Limit ubrogepant use to no more than 8 migraine attacks per 30-day period to prevent medication overuse headache. 1

Medications to Absolutely Avoid

Opioids (hydromorphone, meperidine, codeine) and butalbital-containing compounds should not be used routinely for migraine treatment because they have questionable efficacy, lead to dependency, cause rebound headaches, result in loss of efficacy over time, and carry a two-fold higher risk of medication-overuse headache compared with NSAIDs and triptans. 1, 2

• Opioids should be reserved exclusively for cases where all other evidence-based treatments are contraindicated, sedation is acceptable, and a formal assessment of abuse risk has been completed. 1
• If an opioid must be used, butorphanol nasal spray demonstrates better evidence than other opioids for headache treatment. 1

Contraindications to Triptans and Ergots

Triptans and ergotamine are contraindicated in patients with ischemic heart disease, previous myocardial infarction, coronary artery vasospasm, uncontrolled hypertension, cerebrovascular disease, history of stroke or TIA, or basilar/hemiplegic migraine. 1

• DHE is contraindicated with concurrent triptan use within the past 24 hours, beta-blockers, uncontrolled hypertension, coronary artery disease, pregnancy, and sepsis. 1
• For patients with cardiovascular contraindications, use NSAIDs, acetaminophen, gepants (ubrogepant, rimegepant), or dopamine antagonists (metoclopramide, prochlorperazine). 1

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Preventive Treatment Algorithm

Indications for Preventive Therapy

Preventive therapy is recommended for patients who experience ≥2 migraine attacks per month with disability lasting ≥3 days, who use abortive medication >2 times per week, who have contraindications to or failure of acute treatments, or who have uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura, migrainous infarction). 3

• Additional factors prompting preventive treatment include significant adverse events from acute therapies, strong patient preference for prevention, and cost considerations. 3

First-Line Preventive Medications

Beta-blockers without intrinsic sympathomimetic activity are endorsed as first-line oral preventives, with propranolol 80–240 mg/day and timolol 20–30 mg/day having the strongest evidence. 3

• Metoprolol, atenolol, and nadolol are supported by moderate-quality evidence for migraine prevention. 3
• Topiramate 50–100 mg/day (typically 50 mg twice daily) is the only oral preventive with strong RCT evidence specifically confirming efficacy in chronic migraine and is preferred for patients with obesity due to associated weight loss. 3
• Candesartan is an effective first-line agent, particularly useful for patients with comorbid hypertension. 3

Second-Line Preventive Medications

Amitriptyline 30–150 mg/day is preferred when patients have comorbid depression, anxiety, or sleep disturbances and is superior for mixed migraine + tension-type headache. 3

• Amitriptyline lacks robust RCT evidence for chronic migraine prophylaxis; its efficacy is primarily demonstrated in episodic migraine. 3
• Sodium valproate (800–1500 mg/day) or divalproex sodium (500–1500 mg/day) are strictly contraindicated in women of childbearing potential due to teratogenic effects. 3
• Flunarizine 5–10 mg once daily (typically at night) is an effective second-line agent where available, with proven efficacy comparable to propranolol and topiramate. 3

Third-Line: CGRP Monoclonal Antibodies

CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered when 2–3 oral preventive medications have failed or are contraindicated. 3

• These agents are administered monthly via subcutaneous injection (or quarterly IV for eptinezumab), with efficacy requiring assessment after 3–6 months. 3
• CGRP monoclonal antibodies are significantly more expensive than oral agents, with an annualized cost of $5,000–$6,000. 3

OnabotulinumtoxinA for Chronic Migraine

OnabotulinumtoxinA is the only FDA-approved preventive therapy specifically for chronic migraine (≥15 headache days per month) and should be used as first-line when three oral preventives have failed. 1

• The recommended administration protocol is 155–195 U injected across 31–39 sites every 12 weeks, performed by a neurologist or headache specialist. 1
• Phase III PREEMPT trials demonstrated that onabotulinumtoxinA reduces headache days, headache episodes, cumulative headache hours, and improves quality of life in chronic migraine patients. 1
• Efficacy should be evaluated after 6–9 months of treatment to determine success or failure. 1
• OnabotulinumtoxinA is specifically not recommended for episodic migraine prevention. 3

Implementation of Preventive Therapy

Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases, with an adequate trial period of 2–3 months for oral agents. 3

• The typical effective dose of propranolol is 160 mg once daily, with some patients requiring up to 240 mg daily; doses below 160 mg are generally sub-therapeutic. 3
• Amitriptyline shows greatest efficacy at daily doses ranging from 30 mg to 150 mg, with higher doses within this range often needed to achieve adequate response. 3
• For CGRP monoclonal antibodies, efficacy should be assessed only after 3–6 months. 3
• Consider pausing preventive treatment after 6–12 months of successful therapy (defined as ≥50% reduction in monthly migraine days) to determine if it can be discontinued. 3

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Non-Pharmacologic Measures

Behavioral treatments including biofeedback, relaxation training, and cognitive behavioral therapy are recommended as first-line preventive options and should be offered alongside medication as effective adjuncts. 1, 3

• Neuromodulatory devices can be considered as adjuncts to medication or as stand-alone treatments when medications are contraindicated. 3
• Acupuncture is a potential first-line intervention based on recent positive findings from randomized trials, although it is not superior to sham acupuncture in controlled trials. 1, 3
• Identifying and modifying triggers—such as sleep hygiene, regular meals, hydration, and stress management—can reduce migraine frequency. 3
• Systematic evaluation and management of obesity, excessive caffeine intake, obstructive sleep apnea, and psychiatric comorbidities (depression, anxiety) are essential because these factors perpetuate chronic migraine. 1

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Management of Medication-Overuse Headache (MOH)

Daily use of a triptan for more than 2 days per week (≥10 days/month) or NSAIDs for ≥15 days/month paradoxically increases headache frequency, leading to daily headaches and creating a self-perpetuating cycle. 1

• Abrupt cessation of both the overused triptan and NSAID is recommended; evidence does not support a gradual taper. 1
• Patients should be warned that headache intensity may temporarily worsen for 2–10 days during withdrawal. 1
• Substituting another acute medication during this period is discouraged because it merely transfers the overuse to a different agent. 1
• Initiate preventive therapy immediately with onabotulinumtoxinA (for chronic migraine) or topiramate (higher dose/longer duration, the only oral preventive with proven efficacy in RCTs for chronic migraine) while withdrawing overused medications. 1
• Once MOH resolves (typically 2–4 weeks after discontinuation), acute treatment should be reserved for the most severe, disabling attacks and limited to ≤2 days per week. 1

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Special Populations

Pregnancy and Lactation

Acetaminophen is the safest acute migraine drug during pregnancy and remains the first choice. 4

• Acetaminophen with codeine is also an option during pregnancy. 4
• Sumatriptan may be an option during pregnancy for selected patients and is compatible with breast-feeding. 4
• Valproate is strictly contraindicated in women of childbearing potential due to teratogenic risk; contraception counseling is mandatory. 3

Uncontrolled Hypertension

Acetaminophen 1000 mg is the safest and most appropriate first-line analgesic for intermittent headache when hypertension is uncontrolled, because it does not raise blood pressure or cardiovascular risk. 1

• NSAIDs are contraindicated because uncontrolled hypertension is a relative contraindication; NSAIDs can further elevate blood pressure and increase cardiovascular risk. 1
• After blood pressure control, NSAIDs may be reconsidered because they demonstrate superior efficacy to acetaminophen for most headache types. 1

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Critical Pitfalls to Avoid

• Do not allow patients to increase frequency of acute medication use in response to treatment failure, as this creates a vicious cycle of medication-overuse headache; instead transition to preventive therapy while optimizing acute treatment strategy. 1
• Do not maintain sub-therapeutic doses of preventive medications (e.g., propranolol <160 mg or amitriptyline <30 mg) indefinitely; doses should be optimized before declaring treatment failure. 3
• Do not discontinue preventive therapy prematurely; an adequate trial requires 2–3 months at the target dose before assessing response. 3
• Do not prescribe opioids simply because a patient requests them or reports that "nothing else has worked" without first ensuring adequate trials of NSAIDs, triptans, and appropriate combination therapy. 1
• Do not use Cafergot (ergotamine/caffeine) and triptans within 24 hours of each other due to additive vasoconstrictive effects. 1
• Do not abandon triptan therapy after a single failed attempt—if one triptan is ineffective, try a different triptan, as failure of one does not predict failure of others. 1