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Acute Migraine Treatment

Posted on June 10 2025, By: Cerebral Torque

Acute Migraine Treatment in Adults

Evidence-based strategies for effective acute migraine management

Updated June 2025

Understanding Acute Migraine Treatment

The goal of acute migraine treatment extends beyond pain relief to include rapid restoration of function, prevention of symptom progression, and minimization of headache recurrence.

Key Treatment Principles

Effective acute migraine management is built on five fundamental principles: early intervention during the attack, individualized medication selection based on patient factors, appropriate dosing strategies, consideration of route of administration, and prevention of medication overuse/adaptation headache through proper education and monitoring.

The pharmacologic approach to migraine treatment should be individualized based on attack severity, associated symptoms (particularly nausea and vomiting), treatment setting, cardiovascular risk factors, and prior treatment response. This guide provides evidence-based recommendations for managing acute migraine across different clinical scenarios.

General Approach to Acute Migraine Treatment

Research demonstrates that a stratified care approach, where treatment intensity matches attack severity from the onset, is superior to step-care approaches that start with simple analgesics for all attacks.

Early

Treatment Timing

Medications are most effective when given early in the attack, ideally within the first hour of onset and before allodynia begins

Large

Single Dose Strategy

A large single dose tends to work better than repetitive small doses for most patients

Route

Administration Method

Non-oral routes preferred for patients with significant nausea, vomiting, or gastroparesis which is relatively common during attacks

<15

Days Per Month*

Maximum frequency for simple analgesics; <10 days for triptans and combination analgesics

Early Treatment Benefits

Treating migraine early in the attack, ideally when pain is mild (or earlier with gepants, but more on that later), significantly improves treatment outcomes. Studies show that patients who treat within one hour of onset achieve pain-free response rates of approximately 50% compared to 16% with placebo, even at 30 minutes post-treatment.

Treatment Pearls and Optimization Strategies

Expert Migraine Pharmaceutical Treatment Pearls

The following evidence-based treatment pearls provide practical guidance for optimizing acute migraine therapy across different medication classes and clinical scenarios.

NSAID Treatment Pearls

Timing Strategy Take ASAP after pain onset

NSAID Selection No single NSAID superior - choose based on patient response

Dosing Principle Use lowest effective dose

Celecoxib Option FDA-approved 120 mg oral solution

Triptan Optimization Pearls

Optimal Timing Within 1 hour when pain is mild & prior to allodynia onset

Non-Response Definition Try 3 times before declaring ineffective

Class Non-Response Try 3 different triptans (including SubQ sumatriptan)

Headache Relapse Consider longer half-life triptans + NSAIDs

Frequency Limit <10 days/month

Formulation Selection Strategy

For moderate/severe nausea or vomiting: Prefer intranasal or orally disintegrating formulations. For rapid pain escalation: Consider subcutaneous sumatriptan. For frequent relapses: Switch to longer half-life triptans (eletriptan, naratriptan, frovatriptan) or combine with fast-acting NSAIDs.

CGRP Antagonist (Gepant) Pearls

Prodrome Treatment Can be taken before pain onset

Cardiovascular Safety No vasoconstriction - safe with CV disease

Zavegepant Advantage Intranasal bypasses gastroparesis

Special Cautions Monitor in vascular disease, severe constipation, IBD

Simple Analgesics

Read Our Complete Guide to Simple & Combination Analgesics

Simple analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, provide an effective and cost-efficient first-line approach for many patients with mild migraine attacks. These medications are widely available, well-tolerated, and can be highly effective when used appropriately.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Multiple NSAIDs have demonstrated efficacy in randomized placebo-controlled trials for acute migraine treatment. The evidence supports several specific agents with proven effectiveness and established dosing regimens.

NSAID	Recommended Dose	Maximum Daily Dose	Special Considerations
Aspirin	900-1000 mg	4000 mg	52% headache response vs 34% placebo. Peak plasma: 1-2h; effective with metoclopramide
Ibuprofen	400-600 mg	2400 mg	76% achieve 2-h pain freedom vs 53% placebo. Well-tolerated in clinical practice
Naproxen Sodium	275-550 mg	1375 mg	Faster onset than naproxen base; 14h half-life prevents recurrence
Diclofenac	50-100 mg	150 mg	Oral solution: faster time to peak (within 1h vs 2.5h tablets)
Ketorolac (Parenteral)	30 mg IV or 60 mg IM	120mg (5 days max)	Superior to placebo; effective as chlorpromazine in ED settings

Acetaminophen (Paracetamol)

Acetaminophen is an effective abortive agent for some patients, especially at doses of 1000 mg. A population-based randomized placebo-controlled trial demonstrated 22.4% achieve 2-hour pain freedom versus 11.3% with placebo.

Acetaminophen Dosing Pearl

Start with 1000 mg at onset; if ineffective, may take second dose after 6 hours (maximum two 1000 mg doses in 24h). Peak levels reached in 0.5-1h with elimination half-life of 2h. Well-tolerated with safer GI profile than NSAIDs.

Combination Analgesic Products

Combination products containing acetaminophen, aspirin, and caffeine are a widely available and cost-effective approach to migraine management, particularly for patients with mild to moderate attacks.

Acetaminophen/Aspirin/Caffeine (AAC) Combinations

Typical formulation: Acetaminophen 500 mg + Aspirin 500 mg + Caffeine 130 mg

Clinical efficacy: In early treatment trials, 59.3% achieved pain relief vs 32.8% placebo, with pain freedom detected at 0.5h and sustained through 6h

Usage considerations: Avoid exceeding 3 days per week to prevent medication overuse/adaptation headache

Caffeine's Role in Migraine Treatment

Caffeine acts as a methylxanthine central nervous system stimulant. While not shown to act as a pain reliever independently, it enhances analgesic efficacy when combined with acetaminophen and aspirin. The evidence supporting caffeine as an analgesic adjuvant is consistent, showing enhanced analgesia in combination formulations.

Triptans: The Gold Standard for Moderate to Severe Migraine

Deep Dive into Triptans: Complete Clinical Guide

Triptans (serotonin 1B/1D agonists) are the most extensively studied and effective class of migraine-specific medications. Developed specifically for migraine treatment, these agents work by inhibiting vasoactive peptide release, promoting selective vasoconstriction, and blocking pain pathways in the brainstem.

Triptan	Routes Available	Typical Initial Dose	Maximum 24-Hour Dose	Key Characteristics
Sumatriptan	Oral, Subcutaneous, Intranasal	Oral: 50-100 mg SubQ: 6 mg Nasal: 20 mg	200 mg (oral) 12 mg (SubQ) 40 mg (nasal)	Most formulations available; SubQ has fastest onset; most studied triptan
Rizatriptan	Oral (tablet/ODT/film)	5-10 mg	30 mg	Reduce dose with propranolol; available as ODT and film formulations
Eletriptan	Oral (tablet)	20-40 mg	80 mg	High efficacy profile; avoid with CYP3A4 inhibitors; 40 mg preferred dose
Almotriptan	Oral (tablet)	12.5 mg	25 mg	Well-tolerated; may be better for patients sensitive to side effects
Zolmitriptan	Oral (tablet/ODT), Intranasal	2.5-5 mg	10 mg	Available as ODT; nasal form has less taste disturbance than sumatriptan
Naratriptan	Oral (tablet)	2.5 mg	5 mg	Slower onset, longer duration; may repeat after 4 hours; better tolerated
Frovatriptan	Oral (tablet)	2.5 mg	5 mg	Longest half-life; may be better for menstrual migraine; slower onset

Triptan Selection Strategy

For rapid pain escalation: Rizatriptan (shortest time to peak plasma level) or subcutaneous sumatriptan. For frequent relapses: Frovatriptan, eletriptan, or naratriptan (longer half-lives). For consistent efficacy: Almotriptan or naratriptan (higher oral bioavailability). For better tolerability: Almotriptan, naratriptan, or frovatriptan.

Important Safety Considerations

Triptans have proven to be safe and effective for most migraine patients, with systematic reviews finding no association between triptan use and vasoocclusive cardiovascular events in appropriately selected patients.

Triptan Contraindications and Precautions

Ischemic Heart Disease Contraindicated

Uncontrolled Hypertension Contraindicated

Hemiplegic Migraine Avoid

Brainstem Aura Avoid

Frequency Limit <10 days/month

Drug Interactions Monitor MAOIs, Ergots

Triptan-NSAID Combination Therapy

The combination of triptans with NSAIDs is an effective treatment strategy that is more efficacious than using either drug class alone. This approach has been extensively studied and demonstrates superior outcomes for many patients.

Sumatriptan-Naproxen: The Gold Standard Combination

The most extensively studied combination is sumatriptan with naproxen sodium. A systematic review and meta-analysis found that this combination was more effective than either agent alone for acute migraine treatment.

Clinical Trial Evidence

Two large randomized placebo-controlled trials involving nearly 3000 patients evaluated a fixed-dose combination of sumatriptan succinate 85 mg and naproxen sodium 500 mg. At two hours post-treatment, the combination demonstrated superior headache relief and sustained pain-free response compared to monotherapy with either component.

50%

Pain-Free Response

Sumatriptan-naproxen combination vs 16% placebo at 2 hours

30 min

Early Response

Significant pain-free response seen as early as 30 minutes

CGRP Antagonists

Master CGRP Antagonists: The Gepants Guide

Calcitonin gene-related peptide (CGRP) antagonists, also known as "gepants," are a major advancement in migraine treatment. These medications provide an excellent alternative for patients who cannot use triptans due to contraindications or insufficient response. They are all also effective in the prodromal phase so they can be taken earlier than triptans.

FDA-Approved Options (for acute treatment)

Ubrogepant, Rimegepant, and Zavegepant

Vasoconstriction

Safe for patients with cardiovascular contraindications to triptans

Gepant	Route & Dose	Max Daily Dose	Key Advantages
Ubrogepant (Ubrelvy)	50-100 mg oral	200 mg	May repeat after 2 hours; no cardiovascular contraindications. 21.2% (100 mg) pain freedom vs 11.8% placebo
Rimegepant (Nurtec ODT)	75 mg ODT	75 mg	Also FDA-approved for prevention; effective in triptan non-responders; convenient ODT formulation. 21% pain freedom vs 11% placebo
Zavegepant (Zavzpret)	10 mg intranasal	10 mg	Nasal administration for patients with nausea/vomiting; rapid absorption; bypasses gastroparesis. 24% pain freedom vs 15% placebo

Lasmiditan: A Good Approach for Cardiovascular Patients

Complete Ditans Guide: Lasmiditan Deep Dive

Lasmiditan is a selective serotonin 1F receptor agonist that lacks vasoconstrictor activity. This unique profile makes it an excellent option for patients with cardiovascular contraindications to triptans.

32%

Pain Freedom (200 mg)

vs 15% placebo at 2 hours

50-200 mg

Dosing Range

Initial 50-100 mg, may increase to 200 mg; maximum one dose per 24 hours

8 hrs

Driving Restriction

No driving or machinery operation for 8 hours after dose

Lasmiditan Dosing Pearl

Initial dose of 100 mg. Can decrease to 50 mg for better tolerability or increase to 200 mg for improved efficacy. For elderly patients (65+ years), consider starting with 50 mg due to higher incidence of adverse events. Main side effect is dizziness (dose-dependent).

Ergot Derivatives and Alternative Therapies

Comprehensive DHE Guide: All Formulations & Uses

While less commonly used due to side effect profiles and newer alternatives, ergot derivatives remain important options for specific clinical scenarios, particularly for status migrainosus and patients with frequent headache recurrence. Recent approvals have significantly expanded DHE delivery options.

Dihydroergotamine (DHE) - Multiple FDA-Approved Formulations

Parenteral DHE: 1mg IV/IM (with antiemetic premedication) - gold standard for status migrainosus

Trudhesa (DHE nasal spray): 0.725 mg per spray, maximum 4 sprays per 24 hours (2.9 mg total). Enhanced absorption formulation

Migranal (DHE nasal spray): 0.5 mg per spray, maximum 6 sprays per 24 hours (3 mg total). Original nasal formulation

Brekiya (DHE autoinjector): 1 mg subcutaneous autoinjector for self-administration. First and only DHE autoinjector approved by FDA in 2025. Does not require refrigeration, assembly, or priming. Single-dose device designed for injection into the thigh.

Atzumi (DHE nasal powder): First and only DHE nasal powder utilizing SMART (Simple MucoAdhesive Release Technology) platform. Easy-to-use, easy-to-carry device approved by FDA in April 2025. Demonstrates rapid absorption and sustained DHE plasma levels.

Brekiya Advantages

May provide sustained relief for 24-72 hours. Can be administered at any point during an attack. Ideal for patients with nausea, vomiting, gastroparesis, or inadequate response to oral medications.

Atzumi Clinical Results

Freedom from pain: 37%, 67%, and 86% at 2, 4, and 24 hours respectively. Freedom from most bothersome symptoms: 54%, 80%, and 91%. Headache relief: 67%, 89%, and 94%.

DHE vs Triptans

DHE offers superior sustained relief with lower recurrence rates compared to triptans. The newer formulations (Brekiya autoinjector and Atzumi nasal powder) provide convenient outpatient options for patients who respond well to DHE but want to avoid IV administration. Must maintain 24-hour separation from triptans.

New DHE Formulation Benefits

DHE has been recommended in published migraine treatment guidelines as a first-line acute treatment option since 1946, with significant advantages versus other anti-migraine treatments. However, previous injectable products had disadvantages including invasive and burdensome administration. The new Brekiya and Atzumi formulations address these limitations with patient-friendly delivery systems.

Important DHE Contraindications and Precautions

Contraindications: Pregnancy, coronary artery disease, uncontrolled hypertension, peripheral vascular disease, severe hepatic or renal impairment

Drug Interactions: Strong CYP3A4 inhibitors (ritonavir, clarithromycin). Should not be used with other vasoconstrictive agents or serotonergic migraine medications.

Special Populations: Not indicated for hemiplegic migraine or migraine with brainstem aura. Not approved for pediatric use.

Timing: Must maintain 24-hour separation from triptans to avoid serious cardiovascular effects

Emergency Department Management

Emergency department management of acute migraine has evolved significantly with evidence-based protocols that emphasize rapid, effective treatment while avoiding problematic medications like opioids. The key is aggressive early intervention with proven therapies.

ED Treatment Priorities

The primary goals in the emergency setting include rapid pain relief (ideally to mild or no pain within 2 hours), control of nausea and vomiting, prevention of 48-72 hour headache recurrence, functional restoration for safe discharge, and avoidance of opioid medications which increase return visit rates.

First-Line ED Therapies (Choose One or Combine)

Subcutaneous Sumatriptan 6 mg: Most effective parenteral triptan with onset within 15-30 minutes. Can reduce to 3-4 mg if 6 mg not tolerated. Maximum 12 mg per 24 hours.

IV Prochlorperazine 10mg + Diphenhydramine 25mg: Often superior to sumatriptan in head-to-head ED trials. Prochlorperazine provides both antiemetic and direct antimigraine effects through dopamine D2 antagonism.

IV Metoclopramide 10 mg: Dual mechanism with antiemetic and antimigraine properties. Number needed to treat = 4 for significant pain reduction. Can be repeated if needed.

IV Ketorolac 30 mg (15 mg if elderly or <50kg): Potent anti-inflammatory effects. Avoid in patients with renal impairment or peptic ulcer disease. Limit to 5 days maximum use.

Refractory Cases and Second-Line Options

DHE 1 mg IV + Metoclopramide 10 mg IV: Highly effective for status migrainosus. Must not be used within 24 hours of triptans. Contraindicated in pregnancy and vascular disease.

IV Chlorpromazine 0.1 mg/kg (max 25 mg): Meta-analyses show superior pain relief compared to other acute therapies, but requires cardiac monitoring and blood pressure management.

IV Dexamethasone 4 mg: Reduces recurrence rates from 24-72 hours (NNT=9). A 2023 trial found similar sustained relief rates at 48 hours whether patients received 4 mg or 16 mg dexamethasone.

IV Sodium Valproate 500-1000 mg: Alternative for refractory cases. Faster-acting than oral formulations. Contraindicated in pregnancy due to teratogenicity.

Why Avoid Opioids in Migraine

Multiple studies demonstrate that opioid use for acute migraine increases 7-day return visit rates, promotes central sensitization and chronification, carries addiction potential, and provides inferior pain relief compared to migraine-specific therapies. Professional guidelines universally recommend avoiding opioids for migraine treatment.

Antiemetic Strategies

Antiemetics serve a dual role in migraine management by addressing debilitating nausea and vomiting while providing direct anti-migraine effects through dopamine receptor blockade. Understanding their mechanisms and optimal use is essential for successful treatment across all care settings.

Prochlorperazine (Compazine)

IV/IM: 10 mg
Oral: 5-10 mg
Efficacy: Often superior to sumatriptan in emergency settings
Mechanism: D2 receptor antagonism + antiemetic effects

Metoclopramide (Reglan)

IV: 10 mg
Oral: 10 mg
NNT: 4 for significant pain reduction
Bonus: Prokinetic effects enhance oral medication absorption

Chlorpromazine (Thorazine)

IV: 0.1mg/kg (max 25 mg)
Oral: 25-50 mg
Evidence: Meta-analyses show superior pain relief
Caution: Requires cardiac monitoring for IV use

Haloperidol (Haldol)

IV: 5 mg
Efficacy: Effective for migraine pain relief
Limitations: 80% incidence of sedation and akathisia
Use: Reserve for refractory cases

Critical Safety Protocols

Always co-administer diphenhydramine (12.5-25 mg IV or 25-50 mg oral) with dopamine blockers to prevent akathisia and dystonic reactions. Monitor for QT prolongation with chlorpromazine and haloperidol. Avoid in patients with known cardiac conduction abnormalities or concurrent QT-prolonging medications.

Outpatient Oral Antiemetic Options

Metoclopramide 10 mg oral: Can be taken 30 minutes before migraine-specific therapy to enhance absorption and reduce nausea. Particularly useful for patients with gastroparesis during attacks.

Prochlorperazine 5-10 mg oral: Effective for mild to moderate nausea. May cause sedation, which can be beneficial for some patients during migraine attacks.

Promethazine 12.5-25 mg oral: Alternative option with antihistamine properties. May provide additional benefit for patients with motion sensitivity.

Ondansetron 4-8 mg oral: 5-HT3 antagonist with limited migraine-specific effects but useful for severe nausea without the extrapyramidal side effect risk of dopamine blockers.

Understanding Dual Mechanisms

Dopamine receptor antagonists work through multiple pathways in migraine: direct anti-nociceptive effects in the trigeminal nucleus, modulation of neurotransmitter systems involved in migraine pathophysiology, antiemetic effects addressing gastroparesis, and potential anti-inflammatory actions. This explains their efficacy beyond simple symptom control.

Inpatient Management: Complex and Refractory Cases

Inpatient treatment is reserved for the most challenging cases including status migrainosus (>72 hours), intractable migraine requiring intensive monitoring, medication overuse/adaptation headache withdrawal, and patients with significant comorbidities complicating outpatient management.

Status Migrainosus Protocol

IV Fluid Resuscitation: Address dehydration from reduced oral intake and vomiting. Normal saline or lactated Ringer's 1-2 liters over first few hours, then maintenance based on clinical status.

DHE Protocol (Raskin Protocol): DHE 0.5-1 mg IV every 8 hours with metoclopramide 10 mg premedication. Continue until headache-free for 24 hours or maximum 3 days. Monitor for ergotism signs (rare with proper usage).

Alternative Parenteral Options: IV ketorolac 30 mg every 6 hours (max 5 days), IV valproate 500-1000 mg daily, or continuous antiemetic therapy with metoclopramide or prochlorperazine.

Bridge to Prevention: Initiate or optimize preventive therapy during admission. Common choices include topiramate, propranolol, amitriptyline, or CGRP monoclonal antibodies.

Medication Overuse/Adaptation Headache (MOH/MAH) Withdrawal

Withdrawal Symptoms: Worsening headache, nausea, vomiting, anxiety, and sleep disturbances typically peak at 2-10 days post-cessation depending on the overused medication.

Supportive Care: IV hydration, antiemetics (metoclopramide, prochlorperazine), NSAIDs for breakthrough pain, and short-term corticosteroids (prednisone 60-100 mg daily x 3-7 days with taper).

Bridge Therapy: Initiate preventive medications immediately. DHE protocols can break the cycle while establishing prevention. Generally avoid reintroducing overused medications.

Education and Planning: Comprehensive patient education on MOH/MAH, proper acute medication limits, and long-term prevention strategies before discharge.

Peripheral Nerve Blocks

Expert Guide to Migraine Nerve Blocks

For patients with severe, prolonged attacks or those refractory to standard treatments, peripheral nerve blocks offer an alternative approach with rapid onset and significant efficacy. These procedures are typically reserved for emergency department settings or specialized headache centers.

Greater Occipital Nerve Block

Best evidence. Bilateral blocks with bupivacaine or lidocaine. 31% headache freedom at 30 minutes vs 0% with sham in refractory ED patients. Targets C2-C3 nerve roots.

Sphenopalatine Ganglion Block

Intranasal lidocaine or bupivacaine. 55% achieve 50% pain reduction vs 21% placebo, though anatomical limitations exist.

Supraorbital Nerve Block

Targets trigeminal nerve branches. Useful for frontal headache patterns. Local anesthetic injection at supraorbital notch.

Supratrochlear Nerve Block

Complements supraorbital block for comprehensive trigeminal coverage. Injection medial to supraorbital notch.

Considerations

Patient Selection: Best for refractory cases, patients unable to tolerate medications, or those requiring rapid onset relief in emergency settings.

Duration: Effects typically last 4-72 hours depending on anesthetic used and individual patient factors.

Block Contraindications and Safety

Peripheral nerve blocks are typically reserved for patients with severe, prolonged attacks who have failed standard therapies. Contraindications include local infection at injection site, anticoagulation therapy, and known local anesthetic allergy. Always use aseptic technique and consider anatomical variations that may affect block success.

Evidence Base for Nerve Blocks

A systematic review of nerve blocks for primary headache disorders found that greater occipital nerve blocks showed the strongest evidence, with multiple studies demonstrating significant pain reduction in refractory migraine patients. The sphenopalatine ganglion block also shows promise, particularly for cluster headache and refractory migraine, though technique standardization remains a challenge.

Neuromodulation Devices

Complete Guide to Neuromodulation Devices for Migraine

For patients who cannot tolerate medications, prefer non-pharmacologic approaches, or have refractory migraine, several FDA-cleared neuromodulation devices have demonstrated significant efficacy for acute migraine treatment. These devices offer medication-free alternatives with excellent safety profiles.

External Trigeminal Nerve Stimulation (e-TNS)

Cefaly device provides 20-minute treatment sessions. ACME trial showed mean pain reduction of 3.46 vs 1.78 with sham treatment on 0-10 scale.

Remote Electrical Neuromodulation (REN)

Nerivio smartphone-controlled device. 30-45 minute sessions yield 37% vs 18% pain-free response at 2 hours compared to sham stimulation.

Single-Pulse Transcranial Magnetic Stimulation

sTMS Migraine Therapy from eNeura. 39% vs 22% pain freedom at 2 hours with sustained benefit at 24-48 hours.

Non-invasive Vagus Nerve Stimulation

gammaCore device with 120-second bilateral neck stimulations. 30% vs 20% pain freedom in PRESTO trial, though not statistically significant.

Device Advantages

Neuromodulation devices offer several advantages: no systemic side effects, no drug interactions, can be used with concurrent medications, safe for patients with cardiovascular contraindications to triptans, and no risk of medication overuse/adaptation headache. Most devices are FDA-cleared and covered by many insurance plans.

Medication Overuse/Adaptation Headache Prevention

Understanding Medication Overuse Headache: Prevention & Treatment

All patients receiving acute migraine treatment must be educated about medication overuse/adaptation headache (MOH/MAH) risk. The degree of risk varies between medication classes, and frequency limits differ by medication type.

Medication Class	MOH Risk Level	Recommended Frequency Limit	Special Considerations
Opioids	Highest Risk	<10 days/month	Generally avoid for migraine treatment. Can lead to tolerance, dependence, and addiction
Butalbital Combinations	High Risk	<10 days/month	Can produce tolerance, dependence, and addiction. Withdrawal symptoms can be severe including potential seizures
Triptans	Intermediate to High Risk	<10 days/month	Can lead to MOH/MAH sooner and at lower doses than other treatments
Combination Analgesics	Intermediate Risk	<10 days/month	Combinations with codeine have greater potential for overuse. Caffeine enhances addiction potential
Simple Analgesics (NSAIDs, Acetaminophen)	Lower Risk	<15 days/month	NSAIDs may be protective against chronic migraine. Safest option for frequent use

MOH/MAH Prevention Principle

Limit triptans and combination analgesics to fewer than 10 days per month, while simple analgesics (aspirin, acetaminophen, NSAIDs) should be limited to fewer than 15 days per month. Patients exceeding these limits require preventive therapy evaluation.

Algorithm Example

Effective migraine management requires systematic, algorithm-based approaches that account for attack severity, patient factors, and treatment setting.

Step 1: Initial Assessment

Evaluate Attack Characteristics:

Pain severity (mild, moderate, severe)
Presence of nausea/vomiting
Functional disability level
Time since symptom onset
Previous treatment responses

Patient Factors: Cardiovascular risk, contraindications, medication preferences, cost considerations

Step 2: Mild Attacks (No Significant Nausea/Vomiting)

First-Line Options:

Ibuprofen 400-600 mg OR
Naproxen sodium 275-550 mg OR
Acetaminophen 1000 mg OR
Aspirin 900-1000 mg (± caffeine)

If Inadequate Response: Add triptan for subsequent attacks or combine NSAID + triptan

Step 3: Moderate to Severe Attacks

First-Line Options:

Triptan (oral) ± NSAID OR
Sumatriptan 85 mg + Naproxen 500 mg combination OR
If triptan contraindicated: CGRP antagonist OR lasmiditan

With Significant Nausea/Vomiting:

Non-oral triptan (subcutaneous, nasal) OR
Nasal zavegepant OR
Antiemetic + oral medication

Special Populations and Considerations

Pregnancy and Breastfeeding

Pregnancy-Safe Options

Acetaminophen First-Line

Limited Metoclopramide Acceptable

Triptans (if needed) Second-Line: Prefer sumatriptan, naratriptan, rizatriptan

NSAIDs Avoid - risk of renal injury, oligohydramnios

Ergot Alkaloids Contraindicated

Cardiovascular Disease

For patients with cardiovascular contraindications to triptans, excellent alternatives include CGRP antagonists (ubrogepant, rimegepant, zavegepant), lasmiditan, antiemetics, and NSAIDs (when not contraindicated).

Elderly Patients

Elderly Dosing Modifications

Begin with lower doses due to age-related changes in metabolism. Ketorolac doses should be reduced for patients ≥65 years old. For lasmiditan, consider starting with 50 mg instead of 100 mg due to higher incidence of adverse events in this population.

Cost-Effectiveness and Healthcare Resource Optimization

Understanding the economic implications of different treatment strategies helps optimize both patient outcomes and healthcare resource utilization while maintaining high-quality care.

Generic Triptan Advantage

Generic sumatriptan offers excellent cost-effectiveness at $2-5 per dose compared to $40-60 for branded alternatives, with equivalent efficacy profiles.

Combination Therapy Economics

Triptan + NSAID combinations reduce overall treatment costs through improved first-dose efficacy and reduced need for rescue medications.

Early Treatment Savings

Treating attacks early reduces indirect costs from lost productivity ($2,600/year average) and healthcare utilization significantly.

Prevention Investment

Preventive therapy for frequent migraine often provides superior cost-effectiveness compared to frequent acute treatment.

Summary of Treatment Recommendations

Evidence-based recommendations for acute migraine treatment across different clinical scenarios.

Clinical Scenario	First-Line Treatment	Alternative Options	Key Pearls
Mild Attacks	NSAIDs or Acetaminophen Ibuprofen 400-600 mg Naproxen sodium 275-550 mg Acetaminophen 1000 mg	• Add triptan if inadequate response • Combination analgesics • Triple combination (ASA+acetaminophen+caffeine)	Take as early as possible after pain onset. No single NSAID proven superior - choose based on patient response.
Moderate-Severe Attacks	Triptans ± NSAIDs Sumatriptan + naproxen combination Individual triptan selection based on patient factors	• CGRP antagonists (if triptan contraindicated) • Lasmiditan (for CV patients) • DHE + antiemetic	Take within 1 hour when pain is mild. Try specific triptan 3 times before declaring non-response.
Attacks with Severe Nausea/Vomiting	Non-oral formulations Subcutaneous sumatriptan 6 mg Nasal zavegepant 10 mg Intranasal triptans	• Antiemetics + oral medications • Suppository formulations • IV antiemetics in ED	Intranasal routes bypass gastroparesis. Consider antiemetics to prevent dystonic reactions.
Emergency Department	Parenteral combinations IV prochlorperazine 10 mg + diphenhydramine 25 mg SubQ sumatriptan 6 mg IV metoclopramide 10 mg	• DHE + metoclopramide • IV ketorolac 30 mg • IV valproate (limited evidence)	Add dexamethasone 4 mg IV to prevent recurrence. Avoid opioids as first-line therapy.
Cardiovascular Contraindications	Non-vasoconstrictor options CGRP antagonists (ubrogepant, rimegepant, zavegepant) Lasmiditan Antiemetics	• NSAIDs (if not contraindicated) • Acetaminophen • Neuromodulation devices	Avoid all triptans and ergot alkaloids. CGRP antagonists and lasmiditan lack vasoconstrictor effects.
Refractory/Status Migrainosus	Intensive protocols DHE protocol (Raskin protocol) IV fluid resuscitation Continuous antiemetics	• Peripheral nerve blocks • Neuromodulation devices • Bridge to preventive therapy	Consider MOH/MAH withdrawal. Initiate preventive therapy during admission. Monitor for ergotism with DHE.

Takeaways for Clinical Practice

Effective acute migraine treatment requires early intervention with appropriately selected medications matched to attack severity and patient factors. Triptans remain the gold standard for moderate to severe attacks, while CGRP antagonists provide excellent alternatives for patients with contraindications. Combination therapy often provides superior outcomes to monotherapy, and stratified care approaches are superior to step-care strategies.

Early

Intervention

Treatment within first hour optimizes efficacy across all medication classes

Individual

Approach

Tailor treatment selection to patient factors and attack characteristics

Evidence

Based Care

Follow systematic algorithms supported by high-quality clinical evidence

Essential Practice Points

Individualize Every Approach: Consider attack patterns, patient preferences, comorbidities, prior responses, and lifestyle factors in treatment selection.

Emphasize Early Intervention: Consistently educate patients on treating attacks when pain is mild or during prodrome (for gepants) for optimal outcomes and reduced disability.

Optimize Dosing Strategies: Use adequate initial doses rather than multiple small doses; single large doses provide superior efficacy.

Leverage Combination Therapy: Triptan + NSAID combinations offer enhanced efficacy compared to monotherapy approaches.

Prevent Medication Overuse/Adaptation: Proactively educate on usage limits, monitor patterns, and initiate prevention early.

Consider Newer Alternatives: CGRP antagonists and lasmiditan provide excellent options for triptan-intolerant patients.

Quality Metrics for Success

Pain-Free Response: Target >30% pain-free at 2 hours for optimal treatment outcomes

Functional Restoration: Ability to return to normal activities within 4 hours of treatment

Low Recurrence: <20% headache return within 24-48 hours

Patient Satisfaction: High treatment satisfaction and willingness to use the same therapy again

Safety Profile: Minimal adverse effects and no medication overuse development

"When treating a migraine attack, the goal isn't just to stop the pain, but to help you get back to your normal activities quickly, with treatment that works reliably and keeps the attacks from recurring" - Cerebral Torque

Emerging Therapeutic Targets

The migraine treatment landscape continues to evolve rapidly with novel mechanisms of action, innovative delivery systems, and personalized medicine approaches.

Next-Generation Targets

PACAP Antagonists: Targeting pituitary adenylate cyclase-activating polypeptide pathways shows promise in early trials with novel mechanisms beyond CGRP.

Orexin Modulators: Addressing sleep-wake dysregulation and hypothalamic dysfunction in migraine pathophysiology. This will be especially significant for men with migraine.

NK1 Antagonists: Targeting substance P and neurogenic inflammation pathways that complement existing therapies.

Glutamate Modulators: AMPA and NMDA receptor modulators addressing central sensitization mechanisms.

Personalized Medicine Revolution

Future migraine treatment will likely incorporate genetic markers (CGRP pathway polymorphisms, drug metabolism variants), biomarkers (CGRP levels, inflammatory markers), machine learning algorithms for treatment prediction, and real-time physiologic monitoring to optimize therapy selection for each patient's unique profile and attack characteristics.

Important Disclaimer

This information is for educational purposes only and should not replace professional medical advice. Always consult with healthcare providers for personalized treatment recommendations. Treatment decisions should be based on individual patient factors, contraindications, and clinical judgment. The content presented here is based on current evidence and guidelines but may not reflect the most recent developments in migraine treatment.

References

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Gartlehner G, Dobrescu A, Wagner G, et al. Pharmacologic Treatment of Acute Attacks of Episodic Migraine: A Systematic Review and Network Meta-analysis for the American College of Physicians. Ann Intern Med. 2025;178:507.
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Vestibular Migraine

MigraineScience Blog

Tue, Jun 10, 25