Migraine Treatment: Medications, Preventives, and Regenerative Options

The main medications for migraines fall into two groups: acute drugs taken at the first sign of an attack, led by triptans such as sumatriptan, gepants such as ubrogepant and rimegepant, and NSAIDs such as ibuprofen, and preventive drugs taken on a schedule, including the anti-CGRP monoclonal antibodies (Aimovig, Ajovy, Emgality, Vyepti), the oral gepant atogepant, topiramate, propranolol and Botox. Preventive treatment is recommended when migraines occur on 4 or more days a month, according to the American Academy of Neurology (2012) [5].

Most people start with an over-the-counter NSAID or a combination of aspirin, acetaminophen and caffeine, move to a prescription triptan when that is not enough, and add a preventive when attacks become frequent or disabling. Gepants and the ditan lasmiditan cover patients who cannot take triptans because of heart disease or stroke risk. Regenerative and procedural options such as nerve blocks sit alongside these medications, not in place of them.

Migraine Medications Compared: Acute Versus Preventive

Migraine medications are sorted by when you take them. Acute medications, also called abortive or rescue medications, are taken at the start of an attack to stop it. Preventive medications, also called prophylactic or maintenance treatments, are taken daily, monthly or quarterly to cut the number of migraine days. Many people with frequent migraine use one of each.

The right mix depends on attack frequency, how disabling attacks are, and other conditions such as high blood pressure, depression, insomnia or pregnancy plans. The migraine treatment guide covers the condition-level picture, and the migraine condition overview explains diagnosis and triggers.

Acute Treatment: Stopping an Attack

The goal of acute treatment is to make the migraine go away within 2 hours and keep it from coming back within 24 hours. Timing matters enormously: treating early (within the first hour of headache onset) dramatically improves response rates for nearly every medication class [1].

Triptans

Triptans are serotonin 5-HT1B/1D agonists that work by constricting dilated blood vessels and blocking pain signal transmission in the trigeminovascular system. Seven triptans are available, and they are not interchangeable: patients who fail one may respond well to another [2].

Triptans are contraindicated in uncontrolled hypertension, coronary artery disease, history of stroke, and hemiplegic migraine. These contraindications exclude a significant number of patients, which is where gepants fill the gap. People with hemiplegic migraine in particular are usually steered toward non-vasoconstricting options.

Gepants (CGRP Receptor Antagonists)

Gepants are small-molecule CGRP antagonists that block the same pathway as anti-CGRP monoclonal antibodies but in oral or nasal form for acute use.

• Ubrogepant (Ubrelvy): 50-100 mg oral. 2-hour pain freedom in 19-22% (vs. 12% placebo). No cardiovascular contraindications [3].
• Rimegepant (Nurtec ODT): 75 mg orally dissolving tablet. Dual-approved for both acute treatment and prevention (every other day dosing). 2-hour pain freedom in 21%.
• Zavegepant (Zavzpret): 10 mg nasal spray. Fastest onset gepant. 2-hour pain freedom in 24%. Good option when nausea prevents oral medication.

Gepants lack the vasoconstrictor properties of triptans, which makes them a reasonable option for many patients with cardiovascular disease. They also do not appear to cause medication overuse headache with regular use.

Ditans (5-HT1F Agonists)

• Lasmiditan (Reyvow): 50-200 mg oral. Works on the same serotonin pathway family as triptans but without vasoconstriction. Effective for triptan non-responders. Main limitation: CNS side effects (dizziness, sedation). Classified as Schedule V; patients cannot drive for 8 hours after dosing [4].

NSAIDs and Combination Analgesics

For mild-to-moderate migraines:

• Ibuprofen 400-800 mg: Effective for mild attacks; best taken at onset
• Naproxen 500-750 mg: Longer half-life provides sustained relief
• Aspirin-acetaminophen-caffeine (Excedrin Migraine): OTC combination with good evidence for mild-moderate attacks. Caffeine enhances absorption and has independent analgesic properties
• Diclofenac potassium 50 mg: Faster absorption than diclofenac sodium; good migraine-specific evidence

What is the best over-the-counter migraine treatment?

Ibuprofen and the aspirin-acetaminophen-caffeine combination have the strongest over-the-counter evidence for mild to moderate migraine, and both work best when taken at the first sign of pain. Naproxen sodium is sold over the counter at a lower strength than the prescription doses listed above. Acetaminophen alone is generally less effective than an NSAID, but it is an option for people who cannot take NSAIDs because of stomach, kidney or bleeding concerns.

Over-the-counter painkillers carry the same medication overuse risk as prescription drugs, a threshold set by the ICHD-3 criteria [14] and explained in the medication overuse section below.

Anti-Emetics

Nausea and vomiting accompany many migraine attacks and impair oral medication absorption. Metoclopramide (10 mg) or prochlorperazine (10 mg) given IV or IM are effective both as anti-emetics and as migraine-specific treatments in the emergency department. Ondansetron (Zofran) addresses nausea but lacks direct migraine efficacy.

Preventive Treatment: Reducing Attack Frequency

Prevention is recommended when [5]:

• Migraines occur 4 or more days per month
• Acute treatments are ineffective or poorly tolerated
• Acute medication use exceeds 10-15 days per month (medication overuse threshold)
• Attacks are severely debilitating regardless of frequency
• Hemiplegic migraine, brainstem aura, or prolonged aura is present

Prolonged or unusual aura also calls for a closer look before choosing a drug; our guide to migraine with aura explains which aura features need prompt medical review. A preventive is usually judged a success when it cuts monthly migraine days by half or more, and most need 2 to 3 months at a steady dose before that judgment is fair.

Anti-CGRP Monoclonal Antibodies

The anti-CGRP monoclonal antibodies (often shortened to CGRP mAbs) are the most significant advance in migraine prevention in decades. These injectable antibodies target CGRP or its receptor, providing sustained prevention with monthly or quarterly dosing. In 2024 the American Headache Society updated its position to call CGRP-targeting therapies a first-line option for migraine prevention, rather than a choice reserved for people who had already failed older pills [11].

• Erenumab (Aimovig): 70-140 mg SC monthly. Targets the CGRP receptor. 50% migraine day reduction in 43-50% of patients. Most common side effect: constipation [6].
• Fremanezumab (Ajovy): 225 mg monthly or 675 mg quarterly. Targets CGRP ligand. Quarterly option is unique to this agent.
• Galcanezumab (Emgality): 240 mg loading dose, then 120 mg monthly. Targets CGRP ligand. Also approved for episodic cluster headache [13].
• Eptinezumab (Vyepti): 100-300 mg IV quarterly. Fastest onset of any preventive (effect detectable on day 1 after infusion). The only IV anti-CGRP option.

These agents have minimal systemic side effects and no drug interactions. They are not hepatotoxic and do not require blood monitoring. The main barrier is cost: $600-800/month without insurance, though manufacturer patient assistance programs cover many patients.

Oral Gepants for Prevention

Two gepants are approved for prevention in pill form. Atogepant (Qulipta) is taken once daily and was approved by the FDA for episodic migraine in 2021 after the ADVANCE trial (Ailani, NEJM 2021) showed fewer monthly migraine days than placebo at every dose tested [12]; its label was later extended to chronic migraine. Rimegepant (Nurtec ODT), described in the acute section above, is the only drug approved for both stopping attacks and preventing them, using every-other-day dosing for prevention.

Oral Preventives (First-Generation)

Topiramate, propranolol, metoprolol and valproate (as divalproex) are among the drugs rated Level A, the highest level of evidence, in the 2012 American Academy of Neurology guideline [5]. These older drugs are inexpensive generics, which is why insurers often require a trial of two of them before covering a CGRP antibody. Doctors usually pick the one whose side effect profile also helps a second problem, such as propranolol for high blood pressure or amitriptyline for poor sleep.

OnabotulinumtoxinA (Botox)

Approved for chronic migraine (15+ headache days/month). Thirty-one fixed-site injections across the head and neck every 12 weeks. Reduces headache days by an average of 8-9 per month. Takes 2-3 treatment cycles to reach full effect. Well tolerated; main side effects are injection site pain and neck weakness [7].

Neuromodulation Devices

FDA-cleared devices that modulate pain pathways without drugs:

• Cefaly (external trigeminal nerve stimulation): Worn on the forehead; approved for both acute and preventive use. Reduces migraine days by 2-3 per month.
• SpringTMS/sTMS (single-pulse transcranial magnetic stimulation): Handheld device applied to the back of the head. Can abort aura and treat acute attacks.
• gammaCore (non-invasive vagus nerve stimulation): Applied to the neck; approved for cluster headache and migraine. Modulates trigeminal pain processing.
• Nerivio: Remote electrical neuromodulation worn on the upper arm; controlled via smartphone app. FDA-cleared for acute and preventive use.

Non-Injectable Migraine Prevention Options

Non-injectable migraine prevention includes daily oral preventives, oral gepants and FDA-cleared neuromodulation devices. People who dislike needles, or whose insurance will not cover a CGRP antibody, have several choices that never involve an injection or infusion.

• Daily oral preventives: topiramate, propranolol, metoprolol, amitriptyline, venlafaxine and candesartan, chosen to match other health conditions.
• Oral gepants: atogepant once daily or rimegepant every other day, both acting on the CGRP pathway like the injectable antibodies [12].
• Devices: external trigeminal nerve stimulation, remote electrical neuromodulation, single-pulse TMS and non-invasive vagus nerve stimulation, used at home.
• Behavioral treatments: biofeedback, relaxation training and cognitive behavioral therapy, which have long-standing support in US headache guidelines. Clinics offering biofeedback therapy often work alongside neurologists rather than instead of them.
• Supplements: magnesium, riboflavin and CoQ10, covered in the next section.

Botox and the four anti-CGRP antibodies are the main preventives that do require needles. Eptinezumab is given by IV infusion in a clinic every 3 months rather than as a self-injection.

Supplements with Evidence

Several supplements have level B evidence (probably effective) from the American Academy of Neurology [8]:

• Magnesium: 400-600 mg/day of glycinate, citrate, or oxide. Reduces cortical excitability. Particularly helpful in menstrual migraine and migraine with aura.
• Riboflavin (B2): 400 mg/day. Improves mitochondrial energy metabolism. Takes 3 months for full effect.
• CoQ10: 100 mg three times daily. Mitochondrial cofactor. Evidence from a 2005 RCT showing 48% reduction in attack frequency.
• Feverfew: 50-300 mg/day of standardized extract. Anti-inflammatory via inhibition of prostaglandin synthesis. Mixed evidence but generally safe.
• Butterbur (Petasites): Previously recommended but withdrawn in many markets due to hepatotoxicity concerns from PA (pyrrolizidine alkaloid) contamination. Only use PA-free certified products if considering.

Supplements work slowly and modestly, and quality varies between brands because the FDA does not review supplements before sale. The forms of magnesium differ in absorption and gut tolerance, which this comparison of magnesium types sets out.

Medication Overuse Headache: The Hidden Trap

Using acute migraine medications more than 10-15 days per month causes a paradoxical increase in headache frequency called medication overuse headache (MOH). All acute medications can cause it, but opioids and combination analgesics (butalbital) have the highest risk [9].

The International Classification of Headache Disorders (ICHD-3) sets the line by drug type: 15 or more days a month for simple painkillers such as ibuprofen or acetaminophen, and 10 or more days a month for triptans, ergots, opioids and combination analgesics, sustained for more than 3 months [14].

Treatment requires withdrawal of the overused medication, which causes a temporary worsening (1-2 weeks of increased headaches) before improvement. Bridge therapy with a short course of corticosteroids, naproxen, or gepants helps manage the withdrawal period. Simultaneously starting a preventive medication is essential.

Emerging and Regenerative Approaches

• Nerve blocks: Greater occipital nerve (GON) blocks with local anesthetic and corticosteroid provide 2-4 weeks of relief. Useful as a bridge while preventive medications take effect.
• Trigger point injections: Targeting myofascial trigger points in the cervical and trapezius musculature can reduce migraine frequency in patients with cervicogenic components.
• Sphenopalatine ganglion (SPG) blocks: Intranasal lidocaine applied to the SPG can abort acute attacks. SPG stimulation devices are in clinical trials for cluster headache and migraine.
• Psilocybin: Phase 2 clinical trials are investigating psilocybin for cluster headache and intractable migraine. Preliminary data suggests potential disease-modifying effects through serotonergic pathway modulation [10].
• Ketamine: IV ketamine infusions are being explored for refractory chronic migraine, targeting NMDA receptor-mediated central sensitization.

The evidence for most of these approaches is thinner than for the medications above. Nerve blocks are routine in headache clinics and are often covered by insurance, while ketamine therapy for migraine is off label and usually cash pay. Psilocybin remains a Schedule I substance under federal law, so outside a registered trial it is not a legal migraine treatment; the psychedelic therapy guide explains where the research stands.

Some integrative and regenerative clinics also offer IV infusions of fluids, magnesium and anti-nausea drugs during attacks, along with oxygen, which has good evidence for cluster headache but much less for migraine. Ask any clinic which parts of its migraine protocol are supported by published trials and which are not.

Who Prescribes Migraine Medication?

Primary care physicians, nurse practitioners and physician assistants prescribe most migraine medications, including triptans, gepants and first-line oral preventives. Neurologists, and headache specialists with certification in headache medicine from the United Council for Neurologic Subspecialties (UCNS), usually manage chronic migraine, Botox, CGRP antibodies, infusions and nerve blocks. Pain medicine physicians and anesthesiologists perform many nerve block and SPG procedures.

For care beyond the standard prescriptions, the national directory of migraine treatment clinics lists practices by state and city, including headache, integrative and regenerative clinics. Regenerated.com is free for patients, and listing order is not paid ranking. Featured slots are labeled and capped, and Verified means a clinic completed credential checks, not that it paid more. Inclusion in the directory is not an endorsement, so bring the questions in the treatment plan below to any first visit.

Building a Treatment Plan

1. Track first: Keep a headache diary for 1-2 months to establish baseline frequency, severity, and triggers
2. Optimize acute treatment: Find an effective acute medication and take it early. Avoid opioids and butalbital.
3. Start prevention if indicated: Choose based on comorbidities, side effect profile, and patient preference
4. Add supplements: Magnesium + riboflavin + CoQ10 as adjuncts
5. Address lifestyle factors: Regular sleep, exercise, hydration, stress management, trigger avoidance
6. Reassess every 3 months: Adjust or escalate as needed. Success = 50%+ reduction in migraine days.

Diet and gut health come up often in headache diaries; the migraine diet guide covers the common food triggers and what the research says about elimination diets.

Frequently asked questions

What are the most common medications for migraines?

The most common medications for migraines are triptans such as sumatriptan and rizatriptan, NSAIDs such as ibuprofen and naproxen, and the aspirin-acetaminophen-caffeine combination for stopping attacks. For prevention, doctors most often prescribe topiramate, propranolol, amitriptyline, the anti-CGRP antibodies Aimovig, Ajovy, Emgality and Vyepti, the oral gepants atogepant and rimegepant, and Botox for chronic migraine. The American Academy of Neurology recommends prevention once migraines reach 4 or more days a month.

Is Emgality a triptan?

No. Emgality (galcanezumab) is an anti-CGRP monoclonal antibody, not a triptan. It is injected once a month to prevent migraine attacks, and it does not stop an attack that has already started. Triptans such as sumatriptan are serotonin receptor agonists taken as needed during an attack. Many people on Emgality keep a triptan or gepant for breakthrough attacks. Emgality is also approved to prevent episodic cluster headache.

What is the best over-the-counter migraine treatment?

Ibuprofen and the aspirin-acetaminophen-caffeine combination have the strongest evidence among over-the-counter migraine treatments, especially for mild to moderate attacks treated within the first hour. Naproxen sodium is a longer-acting alternative. Acetaminophen alone helps less but suits people who cannot take NSAIDs. Needing any OTC painkiller on 10 to 15 or more days a month raises the risk of medication overuse headache and is a reason to see a clinician.

Is there non-injectable migraine prevention?

Yes. Non-injectable migraine prevention includes daily pills such as topiramate, propranolol, amitriptyline, venlafaxine and candesartan, plus the oral gepants atogepant (taken daily) and rimegepant (taken every other day). FDA-cleared devices such as external trigeminal nerve stimulation, single-pulse TMS, vagus nerve stimulation and remote electrical neuromodulation are also used at home. Magnesium, riboflavin and CoQ10 have modest supporting evidence. Biofeedback and cognitive behavioral therapy add drug-free options.

How many days a month can I take migraine medication?

Most people should limit acute migraine medication to fewer than 10 days a month for triptans, ergots, opioids and combination painkillers, and fewer than 15 days a month for simple painkillers such as ibuprofen or acetaminophen. Going above those limits for more than 3 months can cause medication overuse headache, according to the ICHD-3 criteria. Gepants appear to carry less of this risk. Frequent use is a signal to start a preventive.

Can regenerative or IV treatments help migraines?

Some can help selected patients, but the evidence is thinner than for standard migraine medications. Greater occipital nerve blocks and SPG blocks have the strongest support and are used in headache clinics as bridges or rescue treatments. IV ketamine for refractory migraine is off label and mostly cash pay, and psilocybin is still limited to clinical trials. These options usually work best alongside an acute medication and a preventive, not as replacements.

Related Reading

• Migraine: The Evidence-Based Guide (Pillar)
• Migraine with Aura: What It Looks Like and When to Worry
• Vestibular Migraine: The Dizziness-Migraine Connection

Sources

1. Lipton RB, Stewart WF. Acute migraine therapy: do doctors understand what patients with migraine want from therapy? Headache. 1999;39(Suppl 2):S20-S26. doi:10.1111/j.1526-4610.1999.00006.x ↩
2. Ferrari MD, Goadsby PJ, Roon KI, et al. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis. Cephalalgia. 2002;22(8):633-658. doi:10.1046/j.1468-2982.2002.00404.x ↩
3. Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the treatment of migraine. N Engl J Med. 2019;381(23):2230-2241. doi:10.1056/NEJMoa1813049 ↩
4. Goadsby PJ, Wietecha LA, Dennehy EB, et al. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain. 2019;142(7):1894-1904. doi:10.1093/brain/awz134 ↩
5. 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 ↩
6. Goadsby PJ, Reuter U, Hallstrom Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123-2132. doi:10.1056/NEJMoa1705848 ↩
7. Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010;30(7):793-803. doi:10.1177/0333102410364676 ↩
8. Holland S, Silberstein SD, Freitag F, et al. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults. Neurology. 2012;78(17):1346-1353. doi:10.1212/WNL.0b013e3182535d0c ↩
9. Bigal ME, Lipton RB. Excessive acute migraine medication use and migraine progression. Neurology. 2008;71(22):1821-1828. doi:10.1212/01.wnl.0000335946.53860.1d ↩
10. Schindler EAD, Sewell RA, Gottschalk CH, et al. Exploratory controlled study of the migraine-suppressing effects of psilocybin. Neurotherapeutics. 2021;18(1):534-543. doi:10.1007/s13311-020-00962-y ↩
11. 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 American Headache Society position statement update. Headache. 2024. ↩
12. Ailani J, Lipton RB, Goadsby PJ, et al. Atogepant for the preventive treatment of migraine. N Engl J Med. 2021;385(8):695-706. ↩
13. Goadsby PJ, Dodick DW, Leone M, et al. Trial of galcanezumab in prevention of episodic cluster headache. N Engl J Med. 2019;381(2):132-141. ↩
14. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211. ↩