Best Migraine Cocktails for Acute Relief: A Full Medication Breakdown

Migraine disease affects over 1 billion people worldwide, including more than 39 million in the United States, making it the 3rd most disabling illness globally, according to the Migraine Research Foundation. For those of us navigating this chronic condition, finding an effective migraine cocktail—a personalized mix of medications and therapies that stop an attack—is often a game-changer.

In the Migraine Strong Facebook community, we talk daily about which acute medications work best, which ones can be combined, and how many triptans are actually available. This article brings together everything you need to know about building a migraine cocktail, including over-the-counter (OTC) options, prescription treatments, second-line rescue meds, and even devices. I’ll also share what works for me personally, as well as treatments for vestibular migraine and emergency care options.

🩺 Disclaimer: This post is written from the perspective of a patient and patient advocate. It is not a substitute for professional medical advice. Please consult your healthcare provider to find the best treatment plan for you.

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What Is a Migraine Cocktail?

A migraine cocktail is a combination of medications—prescription, OTC, and/or natural remedies—used together to treat a migraine attack effectively. The goal is to interrupt the migraine process and relieve symptoms like head pain, nausea, and sensory sensitivity.

It’s important to note that not all medications are safe to combine. Always speak to your doctor or pharmacist before trying a new combination.

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Triptans: First-Line Acute Treatment

Triptans are often the first prescription medication added after OTC treatments have failed. These drugs work by narrowing blood vessels and blocking CGRP (calcitonin gene-related peptide), a protein involved in migraine pain pathways. CGRP causes blood vessels to swell and triggers the inflammation cascade that leads to migraine pain.¹

While sumatriptan (Imitrex) is the most commonly prescribed, not everyone finds it effective—or tolerable. Digestive issues during attacks can also interfere with absorption. In these cases, nasal sprays or injections might provide better relief.

If one triptan doesn’t work, it’s worth trying another. Each is formulated differently. Trying a different triptan or combining it with other medications may lead to better outcomes. Triptans should be limited to 10 days a month or about twice a week to avoid rebound headaches.²

Acute Medications – Triptans

Medication	Brand Name	Dosage	Maximum per Day
Almotriptan	Axert	12.5mg tablet	25mg/day
Eletriptan	Relpax	40mg tablet	80mg/day
Frovatriptan	Frova	2.5mg tablet	5mg/day
Naratriptan	Amerge	1–2.5mg tablet	2 doses/day
Rizatriptan	Maxalt	10mg tablet or ODT	3 doses/day
Rizatriptan/Meloxicam	Symbravo	1 tablet (20mg meloxicam/10 mg rizatriptan)	1 dose/day
Sumatriptan	Imitrex	50–100mg tablet, 40mg nasal spray	200mg/day or 40mg nasal spray
Sumatriptan Injection	Imitrex, STATdose, Sumavel, DosePro	4–6mg subcutaneous	Twice/day
Sumatriptan + Naproxen	Treximet	85mg sumatriptan + 500mg naproxen	2 tablets/day
Zolmitriptan	Zomig	2.5–5mg dissolvable tablet or nasal spray	10mg/day or one nasal spray

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NSAIDs and Other Non-Triptan Acute Medications

NSAIDs such as ibuprofen, naproxen, and diclofenac block the neuroinflammation that fuels migraine pain. These medications may be more effective for fully developed attacks—especially those that strike during the night or early morning.³

NSAIDs can also complement triptans to form a well-rounded migraine cocktail that targets multiple pain pathways.

If used alone, NSAIDs may be taken up to 15 days per month. However, when part of a combination drug like Excedrin Migraine or used in combination with a triptan, they should be limited to 10 days/month to avoid rebound.

Other Acute Medications

Medication	Brand Name	Dosage	Maximum per Day
Diclofenac potassium powder	Cambia	50mg packet	150mg/day
Naproxen/Naproxen sodium	Aleve, Anaprox	220mg or 500mg	1000mg/day
Diclofenac sodium	Voltaren	75mg tablet	2 tablets/day
Ibuprofen	Advil, Motrin	400–800mg	2400mg/day
Excedrin Migraine	–	1–2 tablets	4 tablets/day
Prodrin	–	1–2 tablets	5 tablets/day
Timolol maleate (ophthalmic solution)	–	0.5% solution – 1 drop/eye	2 drops/eye/day

Why Timolol?

Timolol eye drops are a fast-acting beta blocker with no rebound risk. In a small study, they were found to help relieve migraine symptoms.⁴ They work faster than the oral version used preventively and are worth discussing with your doctor. Compounding pharmacies can make a nasal spray that is also a 0.5% solution. The formulation was published in the International Journal of Pharmacy Compounding. You can read more in our article about Timolol for migraine.

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New Migraine-Specific Medications

Recent additions to migraine treatment include CGRP receptor blockers like Ubrelvy, Nurtec, and Zavzpret, as well as Reyvow, which works like a triptan without affecting blood vessels.

Many headache specialists recommend taking these meds early in the attack. They may also be combined with NSAIDs to enhance their effectiveness.

New Migraine Medications

Medication	Brand Name	Dosage	Maximum per Day
Ubrogepant	Ubrelvy	50–100mg tablet	200mg/day
Rimegepant	Nurtec	75mg orally dissolving tablet (ODT)	75mg/day
Lasmiditan	Reyvow	50, 100, or 200mg tablet	1 dose/day
Dihydroergotamine	Trudhesa	1 spray per nostril (upper nasal)	Follow prescription
Zavegepant	Zavzpret	10mg nasal spray (1 spray in 1 nostril)	1 spray/day

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Rescue and Second-Line Treatments

When first-line medications don’t work, rescue meds may be used. These are often prescribed for severe or prolonged attacks and are sometimes combined with Benadryl or anti-nausea meds. Our article on Benadryl for migraine provides more in-depth information.

Second-Line Rescue Medications

Medication	Brand Name	Dosage	Max/Day
Diclofenac sodium	Voltaren	75mg tablet	2 tablets/day
Dihydroergotamine	Migranal	Nasal spray	Per RX
Ketorolac	Toradol, Sprix	Injection 60mg/2ml	2/day
Ketorolac Tablets	–	Oral tablets	2/day
Ketorolac Nasal Spray	Sprix	1 spray per nostril	4 doses/day
Steroids	Prednisone, Dexamethasone	Varies	40–80mg max/day
Ergotamine	Ergomar, Cafergot	Varies	2 tablets/day

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Controversial Rescue Treatments

These medications are generally not recommended due to addiction and rebound risks. They may be prescribed in rare situations. Dr. David Watson notes that when used occasionally, opioids may offer relief.⁵ However, studies show they can lead to central sensitization⁶ and cause rebound headaches when used more than four times per month.⁷

Controversial Treatments

Medication	Brand Name	Max Dose Guidance
Butalbital combos	Fiorinal, Fioricet, Phrenilin, Esgic	As directed, limit per month
Hydrocodone + Acetaminophen	Vicodin, Norco	As directed, limit per month
Hydrocodone + Ibuprofen	Vicoprofen	As directed, limit per month
Oxycodone, Meperidine, Tramadol	Generic	As directed, limit per month

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Anti-Nausea Medications

Nausea is a major symptom for many of us. Thankfully, antiemetics don’t just reduce nausea—they also help abort the migraine attack itself.⁸ Many come in forms that bypass the GI tract, which is often impaired during attacks.

Anti-Nausea Medications

Medication	Brand Name	Formulations
Promethazine	Phenergan	Tablets, lozenges, suppositories
Prochlorperazine	Compazine	IV, tablets, spansules, suppositories
Metoclopramide	Reglan	Tablet, IM, IV
Trimethobenzamide	Tigan	Tablet, lozenges, suppositories
Ondansetron	Zofran	Tablet, ODT (4–8mg)

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Vestibular Migraine Rescue Medications

Dizziness and vertigo from vestibular migraine can be treated with benzodiazepines, antihistamines, and Timolol eye drops. Long-acting benzodiazepines like Xanax and Librium are not recommended because they are ineffective for treating vertigo. There is also the potential for difficult withdrawal syndrome for Xanax.⁹

Timolol drops can be especially helpful because they work quickly and bypass the GI system.¹⁰

Vestibular Migraine Rescues

Medication	Brand Name	Dosage
Lorazepam	Ativan	0.5mg up to 2x/day
Clonazepam	Klonopin	0.5mg up to 2x/day
Diazepam	Valium	2mg up to 2x/day
Alprazolam	Xanax	Not Recommended
Chlordiazepate	Librium	Not Recommended
Meclizine	Bonine, Antivert	25–50mg every 4–6 hours
Diphenhydramine	Benadryl	Follow label
Dimenhydrinate	Dramamine	50mg every 4–6 hours
Timolol Maleate	–	0.5% eye drops, 1 drop/eye (max 2/day)

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Neuromodulation Devices

Devices are becoming a powerful addition to migraine treatment. These devices work by sending electrical or magnetic pulses to specific nerves or areas of the brain. The goal is to disrupt or modulate abnormal nerve activity and reduce pain.

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ER Migraine Cocktails

If you’re experiencing severe pain, vomiting, or stroke-like symptoms, go to the ER. A thunderclap headache that peaks in under 60 seconds can be a sign of bleeding.¹⁶

Common ER Medications for Migraine

Medication	Brand Name
Metoclopramide	Reglan
Prochlorperazine	Compazine
Chlorpromazine	Thorazine
Diphenhydramine	Benadryl
Sumatriptan	Imitrex
Zolmitriptan	Zomig
Ketorolac	Toradol
Dexamethasone	Decadron
Magnesium Sulfate	MgSO₄
Valproic Acid	Depakote

The medications listed above are commonly administered in the ER, as a migraine cocktail, for treatment of migraine attacks.¹⁷

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Building a Migraine Cocktail at Home

Most commonly used combo: A triptan + naproxen sodium (Aleve). Naproxen sodium absorbs faster: “peak levels in 1–2 hours vs. 2–4 hours for regular naproxen.”¹⁸ We also see where doctors recommend adding anti-nausea medication or Benadryl to that migraine cocktail as well. Anti-nausea medications help treat primary head pain as well as nausea.

Ask your doctor what they recommend. I have spent several years working with my headache specialist to find some combinations that work for me.

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My Personal Migraine Cocktail

Catching it early:

• Ubrelvy – Has been shown to treat migraine attacks in the prodrome stage of migraine.
• Ginger – The Migraine Strong Supplement Dispensary offers discounted prices for our readers.
• Timolol eye drops
• Allay Lamp – I find this helps with nausea and pain. Our Allay Lamp review article gives more details.
• Peppermint Oil

When pain has started:

• Frovatriptan + caffeine – I particularly like to add McDonald’s Diet Coke here, but a can of Coke Zero or Diet Coke works for me. I have many friends who will drink coffee, tea or regular caffeinated soda.

If that’s not enough:

• Diclofenac Sodium DR
• Phenergan
• Flexeril (muscle relaxant)

I will also reach for:

• Ice or a heating pad
• Put on my Migrafreeze Hat (code: Freeze15)
• Do a meditation with the Calm app

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When to See a Headache Specialist

If you’re having more than four attacks a month or your OTC meds aren’t working, see a headache specialist. Preventing the shift from episodic to chronic migraine is key. A headache specialist will ensure you are treating each attack effectively and evaluate if a daily migraine preventive might be necessary.

Use the American Migraine Foundation’s tool to locate a specialist in your area. Or try the Neura Health app for virtual care. Read our review article on Neura Health (discount with link) or check out our Instagram grid for live interviews we have conducted with the Neura Health doctors. We really can’t recommend this service enough. One of our writers, Danielle Aberman is a patient and we have recommended Neura Health to multiple family members as well.

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Final Thoughts

Finding the right migraine cocktail takes time, patience, and teamwork with your doctor. You don’t have to figure it out alone.

Follow us on Instagram and Facebook, and join our private Migraine Strong Facebook Group for education, support, and community.

Updated from the original publish date of 4/14/2022.

References:

1. Use of Beta-Blocker Ophthalmic Solution for the Treatment of Migraine
2. American Migraine Foundation, Facebook Live recap
3. American Migraine Foundation Acute Treatments For Migraine
4. Beta Blocker Eye Drops For Treatment of Acute Migraine
5. Spotlight On: Migraine and the Opioid Crisis
6. Migraine Treatment: Current Acute Medications and Their Potential Mechanisms of Action
7. American Migraine Foundation, Facebook Live recap
8. Migraine Treatment: Current Acute Medications and Their Potential Mechanisms of Action
9. Drug Treatment of Vertigo
10. Timolol Eye Drops Effective In Some Patients with Acute Migraine
11. Non-Invasive Vagus Nerve Stimulation – Migraine
12. Acute vestibular migraine treatment with noninvasive vagus nerve stimulation
13. External Trigeminal Nerve Stimulation: Potential Rescue Treatment for Acute Vestibular Migraine
14. Nerivio Migra Devices Shows Success Acute Migraine Treatment
15. Migraine Photophobia Originating in Cone-Driven Retinal Pathways
16. Thunderclap Headache
17. Pharmacotherapy for Primary Headache Disorder in the Emergency Department
18. What is Naproxen?