Migraine Acute and Preventive Treatment: A Practical Guide to Modern Therapy

Clinical Practice Update — Triptans, Gepants, CGRP Monoclonal Antibodies, and the Evolving Treatment Landscape in Adults

This is an original clinical education article informed by current guidelines and evidence. See References below for source documents.

MDA-MIG-2026·15 min read

Clinical Focus

Acute migraine management (NSAIDs, triptans, gepants, ditans), preventive therapy (CGRP-targeting therapies, traditional oral preventives, onabotulinumtoxinA), medication overuse headache, and special populations

Target Audience

Neurologists, primary care physicians, emergency physicians, headache specialists, nurse practitioners, pharmacists

Setting

Primary care, neurology clinics, headache centres, emergency departments

Source Evidence

•AHS 2024 Position Statement — CGRP-Targeting Therapies as First-Line Prevention
•ACP 2025 — Acute and Preventive Treatment of Episodic Migraine in Outpatient Settings
•IHS 2024 — Global Practice Recommendations for Acute Pharmacological Treatment of Migraine
•AAN/AHS 2012 — Pharmacologic Treatment for Episodic Migraine Prevention
•AHS 2021 Consensus Statement — Integrating New Migraine Treatments Into Practice
•EHF/EAN 2022 — European Guideline on Migraine Treatment

Key Clinical Takeaways

The most important actionable points from this Practice Update on migraine acute and preventive treatment.

Migraine acute and preventive treatment decision pathway showing triptans gepants CGRP therapies and medication selection for adults — Overview of modern migraine treatment from acute attack management to long-term prevention.

1Triptans remain the most effective acute treatment for moderate-to-severe migraine — but gepants and lasmiditan now offer options for patients with cardiovascular contraindications or triptan failure → Acute Treatment
2CGRP-targeting therapies (monoclonal antibodies and gepants) are now considered first-line options for migraine prevention by the AHS, without requiring prior failure of older preventives → Preventive Treatment
3The ACP and AHS disagree on first-line prevention: the ACP recommends older oral agents (beta-blockers, topiramate, valproate) before CGRP therapies based on cost; the AHS recommends CGRP therapies as co-equal first-line based on efficacy and tolerability → Where Guidelines Differ
4Consider prevention when attacks occur 4 or more days per month, or when attacks significantly impair function despite acute treatment → When to Start Prevention
5If a triptan is only partially effective, the IHS recommends combining oral sumatriptan (50–100 mg) with naproxen sodium (550 mg) before switching drug class → Acute Treatment
6Never use opioids or butalbital for acute migraine — both increase the risk of medication overuse headache and are explicitly recommended against by ACP and AHS → Drugs to Avoid
7OnabotulinumtoxinA is specifically indicated for chronic migraine (15+ headache days/month) — it is not effective for episodic migraine → Chronic Migraine
8Medication overuse headache (MOH) threshold varies: 10+ days/month for triptans or combination analgesics, 15+ days/month for simple analgesics — always screen for it → Medication Overuse
9Rimegepant has a unique dual role: FDA-approved for both acute treatment (75 mg as needed) and prevention (75 mg every other day) of migraine → Gepants
10Avoid valproate and topiramate in women of childbearing age for migraine prevention — the same teratogenicity concerns as in epilepsy apply → Special Populations

How Should You Treat an Acute Migraine Attack?

Acute migraine treatment should be stratified by attack severity and administered early. The ACP 2025 guideline recommends starting with NSAIDs for mild-to-moderate attacks, escalating to triptans (alone or combined with NSAIDs) for moderate-to-severe attacks, and reserving gepants and lasmiditan for those who fail or cannot tolerate triptans. The IHS 2024 recommendations emphasise trying up to three different triptans before concluding triptan failure, and combining sumatriptan with naproxen sodium as a first-choice combination when triptan monotherapy is only partially effective.

Prescribe an NSAID (ibuprofen 400–600 mg, naproxen sodium 550 mg, or aspirin 900–1000 mg) or paracetamol (1000 mg) as first-line for mild-to-moderate migraine attacks. Add an antiemetic (metoclopramide 10 mg or domperidone 10 mg) if nausea is prominent.

Strong Rec High Evidence ACP 2025 IHS 2024

Prescribe a triptan for moderate-to-severe attacks, or for mild-to-moderate attacks that do not respond to NSAIDs. Sumatriptan (50–100 mg oral, 6 mg SC, or 20 mg nasal) is the best-studied; eletriptan (40 mg) and rizatriptan (10 mg) have evidence of superior efficacy among oral triptans.

Strong Rec High Evidence ACP 2025 IHS 2024 AHS 2021

If a triptan is only partially effective, prescribe a combination of sumatriptan (50–100 mg) and naproxen sodium (550 mg) for subsequent attacks before concluding triptan failure. The IHS recommends trying at least three different triptans before switching class.

Strong Rec High Evidence IHS 2024 ACP 2025

Consider a gepant (ubrogepant 50–100 mg, rimegepant 75 mg, or zavegepant 10 mg nasal spray) for patients who fail, do not tolerate, or have contraindications to triptans. Gepants have no vasoconstrictive effect and are safe in patients with cardiovascular disease.

Moderate Rec High Evidence AHS 2021 IHS 2024

Consider lasmiditan (50–200 mg) as an alternative for patients who cannot use triptans or gepants. It is a 5-HT_1F agonist with no vasoconstrictive properties. Patients must not drive within 8 hours of dosing due to sedation and dizziness.

Conditional Rec Moderate Evidence ACP 2025 AHS 2021

Do not use opioids or butalbital for acute migraine treatment. They increase the risk of medication overuse headache, are associated with worse long-term outcomes, and are explicitly recommended against.

Against High Evidence ACP 2025 AHS 2021

Acute Migraine Medications: A Clinical Comparison by Drug Class

Drug Class	Key Examples and Doses	Best Suited For	Key Limitations
NSAIDs	Ibuprofen 400–600 mg, naproxen sodium 550 mg, aspirin 900–1000 mg	First-line for mild-to-moderate attacks; combination with triptans for moderate-severe	GI risk; MOH risk at 15+ days/month; less effective for severe attacks alone
Triptans	Sumatriptan 50–100 mg PO / 6 mg SC; eletriptan 40 mg; rizatriptan 10 mg	Moderate-to-severe attacks; best evidence base of any migraine-specific acute drug	Contraindicated in uncontrolled HTN, coronary/cerebrovascular disease, hemiplegic migraine; MOH at 10+ days/month
Gepants	Ubrogepant 50–100 mg; rimegepant 75 mg; zavegepant 10 mg nasal	Triptan failure/contraindication; cardiovascular disease; dual acute + preventive use (rimegepant)	Higher cost; less rapid onset than SC sumatriptan; limited long-term safety data vs triptans
Lasmiditan	50–200 mg oral	Triptan AND gepant failure/intolerance; cardiovascular disease (no vasoconstriction)	Significant sedation and dizziness; no driving for 8 hours; Schedule V controlled substance; positioned as last-line by ACP

Always advise patients to take acute medications early in the attack for maximum efficacy.
For severe nausea or vomiting, use non-oral formulations: SC sumatriptan, nasal zolmitriptan, nasal zavegepant, or rectal NSAIDs.

When and How Should You Start Preventive Therapy?

Preventive therapy is indicated for approximately 40% of people with migraine but is used by far fewer. The AHS recommends considering prevention when attacks occur 4 or more migraine headache days per month, or when attacks cause significant disability despite acute treatment. The treatment landscape has been transformed by CGRP-targeting therapies — the AHS now considers these first-line alongside traditional oral preventives.

Consider initiating CGRP-targeting therapy (monoclonal antibodies: erenumab, fremanezumab, galcanezumab, eptinezumab; or oral gepants: atogepant, rimegepant) as a first-line preventive option. Initiation should not require prior failure of older preventive drug classes.

Strong Rec High Evidence AHS 2024

Prescribe a traditional oral preventive when cost is a barrier, when the patient prefers oral daily therapy, or when comorbidities favour a specific agent: propranolol or metoprolol (hypertension, anxiety), amitriptyline (insomnia, tension-type headache), topiramate (obesity — but NOT in women of childbearing age), venlafaxine (depression, anxiety — Level B evidence).

Strong Rec High Evidence AAN/AHS 2012 ACP 2025

Prescribe onabotulinumtoxinA (155–195 units, 31–39 injection sites, every 12 weeks) for patients with chronic migraine (15+ headache days per month, of which at least 8 have migraine features). It is not effective for episodic migraine.

Strong Rec High Evidence AHS 2021

Do not prescribe valproate or topiramate for migraine prevention in women of childbearing age. Both carry significant teratogenic risk. Note that lamotrigine is NOT effective for migraine prevention — use a CGRP-targeting therapy, beta-blocker, venlafaxine, or amitriptyline instead.

Against High Evidence AAN/AES/SMFM 2024

Clinical Pearl: Erenumab was superior to topiramate in the HER-MES head-to-head trial for migraine prevention, with significantly better tolerability. This is one of the few direct comparison studies between a CGRP therapy and a traditional preventive, and it provides indirect evidence supporting the AHS position that CGRP therapies should not be considered inferior to traditional agents.

Clinical Decision Pathway

Managing Migraine: 4 Questions

Question 1: How severe is the attack?

Mild-to-moderate → NSAID or paracetamol (+/- antiemetic). If inadequate → triptan next attack.

Moderate-to-severe → Triptan (oral or non-oral). If partially effective → combine sumatriptan + naproxen sodium.

Triptan failure/contraindication → Gepant (ubrogepant, rimegepant, zavegepant). If gepant fails → lasmiditan.

Question 2: Does this patient need prevention?

Yes if: 4+ migraine headache days/month, OR attacks cause significant disability despite acute treatment, OR acute medication overuse risk.

Question 3: Which preventive should I choose?

Episodic migraine → CGRP mAb or oral gepant (AHS first-line), OR traditional oral (beta-blocker, amitriptyline, topiramate [not in women of childbearing age], venlafaxine).

Chronic migraine (≥15 days/month) → OnabotulinumtoxinA, CGRP mAb, or combination of both.

Comorbid cardiovascular disease → Avoid beta-blockers if asthma/COPD; CGRP therapies are safe.

Woman of childbearing age → Avoid valproate and topiramate. Prefer beta-blocker, amitriptyline, or CGRP mAb (discontinue before conception if possible).

Question 4: Is there medication overuse?

Screen: triptans/combination analgesics at 10+ days/month, simple analgesics at 15+ days/month.

If MOH present → Start preventive therapy AND counsel on reducing acute medication use. CGRP mAbs have shown efficacy in patients with medication overuse without requiring detoxification first.

Evidence in Context

Where AHS and ACP Disagree on Prevention

The AHS 2024 position statement recommends CGRP-targeting therapies as first-line for migraine prevention, co-equal with traditional oral agents, based on extensive Class I trial data, long-term safety, and superior tolerability. The ACP 2025 guideline, in contrast, recommends beta-blockers, topiramate, and valproate as first-line for episodic migraine prevention based on a network meta-analysis that prioritised cost-effectiveness. The AHS has publicly responded, noting that the ACP analysis excluded chronic migraine data, used outdated trial methodology comparisons, and did not account for real-world effectiveness, treatment persistence, or the multiple prior treatment failure populations in which CGRP therapies excel. In practice, the choice depends on patient preference, comorbidities, cost/access, and payer requirements.

Gepants: The Dual-Role Revolution

Rimegepant is unique among migraine drugs in having FDA approval for both acute treatment (75 mg as needed) and prevention (75 mg every other day). Atogepant is approved for prevention only (10 mg, 30 mg, or 60 mg daily for episodic migraine; 60 mg daily for chronic migraine). Real-world persistence data from 2025 show that rimegepant users have significantly higher 12-month treatment persistence than triptan users (approximately 76% vs 54%), suggesting superior patient satisfaction and tolerability. Gepants have no vasoconstrictive properties and can be safely used in patients with cardiovascular disease — a major advantage over triptans.

What We Still Don’t Know

Long-term CGRP blockade safety: CGRP has roles in cardiovascular protection and wound healing. Long-term safety data beyond 5 years are still accumulating. No safety signals have emerged to date, but continued pharmacovigilance is warranted.

Head-to-head CGRP comparisons: There are very few trials directly comparing CGRP mAbs to each other or to gepants for prevention. Clinicians choose based on route, frequency, and individual response.

Gepant safety in pregnancy: Data are extremely limited. CGRP mAbs and gepants are generally discontinued before conception, but real-world pregnancy exposure data are needed.

Optimal duration of preventive therapy: When to stop a working preventive is poorly defined. CGRP mAb discontinuation studies show relapse in many patients, but some maintain improvement.

References

1.Charles AC, Digre KB, Goadsby PJ, Robbins MS, Hershey A; American Headache Society. Calcitonin Gene-Related Peptide-Targeting Therapies Are a First-Line Option for the Prevention of Migraine: An AHS Position Statement Update. Headache. 2024;64(4):333–341. doi:10.1111/head.14692
2.Puledda F, Sacco S, Diener HC, et al. International Headache Society Global Practice Recommendations for the Acute Pharmacological Treatment of Migraine. Cephalalgia. 2024;44(8):3331024241252666. doi:10.1177/03331024241252666
3.Qaseem A, Cooney TG, Etxeandia-Ikobaltzeta I, et al. Prevention of Episodic Migraine Headache Using Pharmacologic Treatments in Outpatient Settings: A Clinical Guideline From the ACP. Ann Intern Med. 2025;178:426–433. doi:10.7326/ANNALS-24-01052
4.Silberstein SD, Holland S, Freitag F, et al. Evidence-Based Guideline Update: Pharmacologic Treatment for Episodic Migraine Prevention in Adults. Neurology. 2012;78(17):1337–1345. doi:10.1212/WNL.0b013e3182535d20
5.Ailani J, Burch RC, Robbins MS; American Headache Society. The American Headache Society Consensus Statement: Update on Integrating New Migraine Treatments Into Clinical Practice. Headache. 2021;61(7):1021–1039. doi:10.1111/head.14153
6.Qaseem A, Etxeandia-Ikobaltzeta I, Engel S, et al. Pharmacologic Treatments of Acute Episodic Migraine Headache in Outpatient Settings: A Clinical Guideline From the ACP. Ann Intern Med. 2025;178:434–442. doi:10.7326/ANNALS-24-03095

How to Read the Evidence Tags

Every recommendation carries two tags. These are Medaptly’s own simplified interpretations for educational clarity.

Recommendation Strength

Tag	Meaning	In Practice
Strong Rec	Benefits clearly outweigh risks.	Standard practice.
Moderate Rec	Evidence favours benefit; some uncertainty.	Most patients should receive this.
Conditional Rec	Benefit less certain; individualise.	Shared decision-making.
Against	No benefit or risks outweigh benefits.	Avoid.

Evidence Quality

Tag	Meaning	Confidence
High Evidence	Multiple RCTs or meta-analyses.	Very confident.
Moderate Evidence	Single RCT or large observational studies.	Reasonably confident.
Low Evidence	Expert consensus or small studies.	Less certain.

These are Medaptly’s simplified interpretations. For the full classification systems, consult the original documents in References.

Article Information

For Educational Purposes Only. This is original clinical education content informed by current published guidelines and clinical evidence. It does not constitute medical advice, is not endorsed by any guideline body (AHS, AAN, ACP, IHS, or any other organisation), and does not replace individualised clinical judgement, institutional protocols, or local formulary guidance. Drug dosages should always be verified against current prescribing information before prescribing. Readers are encouraged to consult the original source guidelines listed in the References section for the full evidence review and complete recommendation sets.