Adobe Stock

If you have migraine disease, you know how challenging it can be to deal with this complex neurological condition. People have different medical histories and reactions to medications; the medication that works wonders for your best friend might not do anything for you!

Trial and error to find what works best is often needed, and some only have success with combining medications to treat their migraine attacks, using mixtures of everything from recent scientific breakthroughs to familiar options already in their medicine cabinets.

One of those familiar options is an antihistamine called diphenhydramine. You might know it as Benadryl. Why is an allergy treatment popular among people with migraine? Here’s what we know about Benadryl and migraine, how it may help relieve symptoms, and how to try it safely.

What to Know About Benadryl

Benadryl is the brand name for the antihistamine diphenhydramine in the United States and Canada. Histamine handles several functions in the human body, but the one you probably know best is in the immune system. If you’re exposed to something you’re allergic to, your body thinks that substance is a threat and releases histamine to fight it. The result? Classic allergy symptoms like a stuffy or runny nose, sneezing, and itchy eyes and skin.

Diphenhydramine works by counteracting histamine at the H1 histamine receptors that trigger those allergy symptoms. It also inhibits a neurotransmitter called acetylcholine at central and peripheral nervous system nerve endings. By blocking acetylcholine, diphenhydramine and other “anticholinergic” medications interfere with the parasympathetic part of the autonomic nervous system. The autonomic nervous system manages bodily functions that happen on their own without you having to think about them, like breathing, heart rate, digestion, and body temperature. Anticholinergic medications like Benadryl may also impair your memory, impact cognitive function (“brain fog”), and trigger insomnia OR sleepiness.

“Histamine is believed to contribute to migraine pathophysiology, as evidence shows the release of histamine during a migraine attack, which is believed to induce further neuro-inflammation," says Fred Cohen, MD, a certified headache specialist, assistant professor of medicine and neurology at the Icahn School of Medicine at Mount Sinai in New York City, and headache specialist advocate on TikTok.

“As an H1 antihistamine, it may provide relief by mitigating histamine-related pathways or through its sedative effects,” says Dr. Cohen.

Benadryl Works Best in Combination With Other Treatments

Although there is insufficient evidence to recommend it as a stand-alone acute migraine treatment, Benadryl works best in combination with other medications.

Benadryl is a frequent ingredient in the “migraine cocktail,” the nickname for an intravenous (IV) treatment used in emergency departments or urgent care centers to break a severe migraine attack that hasn’t responded to acute treatments. While every provider has a different preferred “recipe” for an IV migraine treatment, the most common versions include anti-nausea medications, anti-inflammatory medications, analgesics, antiemetics, and diphenhydramine.

Migraine Again

As an ingredient in the migraine cocktail, Benadryl may also counteract the side effects of anti-nausea drugs like prochlorperazine (Compazine or Compro), promethazine (Phenergan), and metoclopramide (Reglan). While these anti-nausea medications can be effective, they may also cause side effects like akathisia, an uncontrollable urge to move (especially in the legs), or dystonia, a painful involuntary contraction of muscles. Typically, these side effects are more likely to happen the more those anti-nausea medications are taken; it’s less common to experience them after one-time usage in a migraine cocktail.

Many people with migraine also include over-the-counter (OTC) Benadryl in their at-home acute treatment toolkits, usually in combination with OTC analgesics or anti-inflammatories, or migraine-specific treatments like triptans and gepants.

What the Research Says About Benadryl for Migraine

Is Benadryl an effective part of the IV migraine cocktail? The results of research into emergency migraine treatment are mixed.

“Some studies suggest it provides additional relief in emergency settings, particularly when used alongside anti-emetics such as prochlorperazine,” says Cohen, an author and participant in several studies. “However, other studies indicate no significant added benefit in terms of overall migraine pain relief,” says Cohen.

Whether or not Benadryl helps in a migraine cocktail depends on which medicines it’s working with, says Gretchen Tietjen, MD, distinguished university professor emeritus of neurology at the University of Toledo College of Medicine and Life Sciences in Ohio.

“One interesting study looked at Reglan and Benadryl versus Reglan alone. They both worked, but the addition of Benadryl didn't add benefit to headache treatment and didn't necessarily do any better at preventing side effects," says Dr. Tietjen.

“But in a randomized study of IV prochlorperazine (Compazine) and Benadryl against hydromorphone (Dilaudid), an opiate, they found that the Compazine and Benadryl worked better than the opiate for acute migraine,” says Tietjen.

A subsequent study demonstrated that the Compazine-Benadryl combination was more effective than Dilaudid at reducing or eliminating migraine-related symptoms like nausea, photophobia, and phonophobia.

How to Try Benadryl for Migraine

At home: If you don’t know how you react to Benadryl, proceed with caution. Do not try it at home without consulting your healthcare provider. If you do try it, make sure you do not have to drive, operate machinery, or perform any activities with a risk of falling or injury (like handling sharp objects or a stove).

Benadryl and generic versions of diphenhydramine tablets come in 25 milligram (mg) and 50 mg doses per tablet for adults; children's formulas come in 12.5 mg doses. The maximum daily dose should not exceed 300 mg.

“If patients are using their acute medications and they help some, but they’re not able to fall asleep or get the results they want, and they don’t have access to newer medications like gepants, they can try a small dose of Benadryl starting at 25 mg and see if that helps,” says Tietjen.

“But they should be aware of side effects and talk to their physician. The patient you always worry about is the one who should be on preventive drugs and is getting migraine attacks frequently and using Benadryl a lot,” advises Tietjen.

In the emergency department: If you visit an urgent care center or emergency department for help with an intractable migraine attack, doctors will likely decide what ingredients to put in your migraine cocktail.

When you are discharged, you’ll probably get a list of the medications they used in your IV. It’s a good idea to save it with your notes about your response to that recipe and share that information with your primary care provider.

RELATED: How My Migraine Treatment Protocol Makes ER Visits Easier

What Community Members Think About Using Benadryl for Migraine

We asked Migraine Again readers on social media about their experiences using Benadryl for migraine. Some say it works for them in IV or at home in combination with other medications.

Any time at the hospital for my migraines, I get Reglan, Toradol, and Benadryl with a magnesium drip and fluids. It works every time!!! Before I'm admitted, my blood pressure is usually very high, and when they check it again before they release me, it's back to normal. — Katie R.

I use Benadryl in my cocktail at home! It helps a ton. I use promethazine, 2 Excedrin, Nurtec, and a Benadryl. — Kiera K.

Benadryl puts me to sleep so my sumatriptan can work! — Elizabeth P.

Some say it didn’t work for them.

Benadryl does absolutely nothing for me. It doesn't matter if it is IV or pill form. — Terra A.

NEVER! It's useless! — Amanda S.

Several readers reported intolerable side effects.

Nope, Benadryl makes me feel so anxious, like I want to crawl out of my skin. Took a few different cocktails to figure out which ingredient was the cause. — Diane W.

Benadryl GIVES me a terrible migraine that I can't shake for the whole day. — Ashlee L.

Possible Side Effects of Benadryl for Migraine

Benadryl’s most common side effects include drowsiness, dizziness, dry mouth, constipation, and a “hangover” feeling of drowsiness the following day if you use it at night. You should not drive, operate machinery, or handle dangerous objects after taking Benadryl.

More serious side effects include pounding heartbeats or “fluttering” in the chest, painful or difficult urination, or confusion. If you have signs of an allergic reaction after taking Benadryl, such as sudden difficulty breathing or swelling of the face, lips, tongue, and/or throat, seek emergency medical care immediately.

“Benadryl is typically avoided in elderly patients due to causing cognitive impairment,” says Cohen. Older patients may be at increased risk of injury from falls if Benadryl makes them sleepy or unsteady.

Using Benadryl long term could come with safety issues. Several large medical studies suggest that long-term regular use of anticholinergic medications is associated with an increased risk of developing dementia. However, a 2019 case-controlled study of over 280,000 patients ages 55 and older reported no significant increase in dementia risk associated with antihistamines compared with anticholinergic medications for other conditions.

If you find yourself using Benadryl or any other acute treatments more than once a week, please talk to your healthcare provider about preventive treatments for migraine. By taking into account your risk factors, migraine frequency, and medications, your provider can determine your best course of action for managing your attacks.

Main Points

A common antihistamine called diphenhydramine (better known by the brand name Benadryl) is a frequent ingredient in the “migraine cocktail,” a combination of medications used intravenously in emergency departments to treat people with intractable migraine attacks. Research suggests that Benadryl can help relieve migraine symptoms and reduce the side effects of other cocktail ingredients, although the results vary widely depending on the individual patient and the specific medications used.
Although Benadryl is not a stand-alone acute treatment for migraine, some people with migraine say that adding OTC Benadryl to their usual at-home acute medication gives them more relief than the acute medication alone.
Occasional use of Benadryl in an acute migraine treatment combination is likely safe for patients who can tolerate Benadryl. The long-term safety is less clear, so talk to your doctor if you find yourself taking Benadryl for migraine regularly.
Even OTC medications carry risks. Do not use Benadryl if you have had a bad reaction to it before. Don’t drive or operate machinery or dangerous objects after taking Benadryl (or any medication) until you know how it affects you. Benadryl may make many people drowsy, but it can cause insomnia and anxiety in some patients. Benadryl may cause cognitive impairment in elderly patients.
Everyone with migraine disease needs a different treatment plan. Talk to your healthcare provider about all of your options, including acute treatments, preventive treatments, lifestyle adaptations, and more, to find your way to more good days!

Have you tried Benadryl for migraine relief? Did it help? Share your lessons learned with other migraine warriors on TIPPI.

Lisa Smith

Lisa Smith is a writer and patient advocate from Massachusetts. Her experiences with a decade of chronic migraine inspired her advocacy work, including a new career narrating professional medical education material. In addition to Migraine Again, she has written for the Association of Migraine Disorders and the National Migraine and Headache Awareness Month websites.

Home

Is Benadryl for Migraine Actually Helpful? What You Should Know