Migraine Management: Evidence‑Based Recommendations

Acute Treatment of Migraine

• NSAIDs (e.g., ibuprofen 400‑800 mg, naproxen sodium 500‑825 mg, aspirin 1000 mg) are recommended as first‑line therapy for mild‑to‑moderate attacks, supported by the strongest available evidence. 1
• Early treatment while pain is still mild significantly improves 2‑hour pain‑free rates and 24‑hour sustained relief compared with treating established moderate‑to‑severe pain. 1
• Limit all acute medications to ≤2 days per week (≈10 days/month) to avoid medication‑overuse headache (MOH). 1
• Triptans (oral sumatriptan 50‑100 mg, rizatriptan 10 mg, eletriptan 40 mg) are first‑line for moderate‑to‑severe attacks or when NSAIDs fail after 2‑3 episodes, with strong evidence for efficacy. 1
• Combination of sumatriptan 50‑100 mg + naproxen sodium 500 mg yields an additional 130 patients per 1,000 achieving sustained pain relief at 48 h and 90 per 1,000 achieving pain relief at 2 h versus either agent alone. 1
• If a specific triptan fails after 2‑3 attacks, switching to a different triptan is advised because failure is not predictive across the class. 1
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (≈59 % pain‑free at 2 h) with onset within 15 min for rapid progression or significant nausea/vomiting. 1
• Intranasal sumatriptan (5‑20 mg) or other nasal spray triptans are useful when early nausea/vomiting limits oral intake. 1
• Ubrogepant 50‑100 mg or rimegepant are third‑line options for patients who cannot use triptans (e.g., cardiovascular disease) and should be limited to ≤8 attacks per 30 days. 1
• In emergency settings, IV metoclopramide 10 mg + ketorolac 30 mg is recommended as a first‑line combination for rapid relief with minimal rebound risk. 1
• IV dihydroergotamine 0.5‑1.0 mg may be used as monotherapy when NSAIDs are contraindicated, repeatable hourly up to a maximum of 2 mg per day. 1
• IV prochlorperazine 10 mg is an effective alternative to metoclopramide for acute headache relief. 1
• Triptans are absolutely contraindicated in patients with ischemic heart disease, prior myocardial infarction, coronary vasospasm, uncontrolled hypertension, cerebrovascular disease, prior stroke/TIA, or basilar/hemiplegic migraine. 1
• Opioids and butalbital‑containing compounds should be avoided for migraine because they have low efficacy, double the risk of MOH, and high abuse potential; reserve only for refractory cases after formal risk assessment. 1

Preventive Therapy Initiation

• Begin preventive treatment when a patient experiences ≥2 migraine attacks per month with ≥3 days of disability, uses abortive medication >2 days/week, has contraindications or failure of acute therapies, or has atypical migraine patterns. 2

First‑Line Preventive Agents

• Propranolol 80‑240 mg/day (or timolol 20‑30 mg/day) is a first‑line beta‑blocker with strong randomized controlled trial (RCT) evidence for migraine prevention. 2
• Topiramate 50‑100 mg/day (typically divided BID) has robust RCT support for chronic migraine and is preferred in patients with obesity due to associated weight loss. 2
• Candesartan is a first‑line option especially useful when hypertension co‑exists. 2

Second‑Line Preventive Agents

• Amitriptyline 30‑150 mg/day is favored for comorbid depression, anxiety, or sleep disturbance, though RCT evidence is stronger for episodic rather than chronic migraine. 2
• Sodium valproate 800‑1500 mg/day (or divalproex 500‑1500 mg/day) is effective but strictly contraindicated in women of child‑bearing potential; contraception counseling is mandatory. 2

Third‑Line Preventive Options

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) are indicated after failure or contraindication of 2‑3 oral preventives; administered subcutaneously monthly with efficacy assessment at 3‑6 months. 2

• OnabotulinumtoxinA is the only FDA‑approved preventive for chronic migraine, given as 155‑195 U across 31‑39 sites every 12 weeks; benefits are evaluated after 6‑9 months and include reductions in headache days and improved quality of life. [1][2]

• Start oral preventives at low dose and titrate slowly, allowing a trial of 2‑3 months; CGRP antibodies require 3‑6 months, and onabotulinumtoxinA 6‑9 months to determine response. 2
• Utilize headache diaries (paper or digital) to track frequency, severity, disability, treatment response, and adverse effects; this validated tool enhances accuracy and aids trigger identification. [1][2]
• Consider a trial discontinuation after 6‑12 months of successful therapy; a ≥50 % reduction in monthly migraine days is generally regarded as a successful outcome. 2

Medication‑Overuse Headache (MOH)

• Abrupt cessation of overused triptans and NSAIDs is recommended; tapering is not supported by evidence, though patients should be warned of a transient worsening of headache intensity for 2‑10 days during withdrawal. 1
• Do not substitute another acute medication during withdrawal, as this merely transfers the overuse to a different agent. 1
• After withdrawal, limit acute treatment to ≤2 days per week to prevent recurrence of MOH. 1

Special Populations

Children and Adolescents (Evidence from JAMA Neurology)

• Ibuprofen is the preferred analgesic for acute migraine pain in children and adolescents. 3
• For adolescents, acute options include oral sumatriptan + naproxen, intranasal zolmitriptan or sumatriptan, oral rizatriptan ODT, or oral almotriptan. 3
• Placebo responses are comparable to active medication in many pediatric trials; clinicians should discuss the modest incremental benefit of preventive agents with patients and families. 3
• Preventive options with supporting evidence in youth include amitriptyline combined with cognitive‑behavioral therapy, topiramate, and propranolol; teratogenic risks of topiramate and valproate must be addressed with contraception counseling and folate supplementation when relevant. 3

Uncontrolled Hypertension

• Acetaminophen 1000 mg is the safest first‑line analgesic when blood pressure is uncontrolled, as NSAIDs may raise blood pressure and cardiovascular risk. 1
• After achieving blood pressure control, NSAIDs may be reconsidered because they demonstrate superior efficacy to acetaminophen for most headache types. 1