Benadryl (diphenhydramine) is a common antihistamine that’s typically used for cold symptoms, allergies, and itching and as a sleep aid. But sometimes it’s recommended for people with multiple sclerosis (MS) before they undergo infusion treatments for relapsing-remitting MS and other forms of the disease. Diphenydramine can help lower the risk of adverse effects — such as allergic reactions — to some MS medication infusions.

MyMSTeam members have shared their experiences with diphenhydramine. “I had an infusion on Monday, and it went well, except the diphenhydramine makes me sooooo tired,” said one member.

Another member described their infusion sessions, saying, “I tend to have a diphenhydramine hangover the rest of the day and the next day. Other than that, I’m good.”

Here’s more on why diphenhydramine is used with some MS treatments and how you can prepare for possible side effects.

Diphenhydramine and MS Treatments

MS providers sometimes administer an antihistamine such as diphenhydramine to help prevent or reduce an unwanted reaction to an infusion of an MS medication. Antihistamines are drugs that block histamine, a chemical produced in the immune system when an allergic reaction is triggered. Histamine can cause allergy symptoms, such as itchy skin, rash, and hives.

Diphenhydramine and other antihistamines are administered either orally or directly through a vein via intravenous (IV) injection. Oral diphenhydramine is available over the counter (OTC). Injected diphenhydramine requires a prescription or order and is given by a healthcare professional before an MS infusion.

Your healthcare team may give you other medications as pretreatment 30 minutes before your MS treatment. These medications may be administered in addition to or instead of diphenhydramine:

• Other antihistamines, such as cetirizine
• Corticosteroids, such as prednisone or methylprednisolone
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen
• Pain relievers, such as acetaminophen

Your healthcare team may give you diphenhydramine and other medications as pretreatment 30 minutes before your MS treatment.

Infusion Reactions With MS Treatments

Infusion reactions are strong responses that can develop during or shortly after receiving an MS infusion treatment. The possibility of infusion-related reactions is one reason that some MS treatments are given in a clinic setting under medical supervision.

These responses can occur because the body may view the drug as an invader or a threat, and your immune system creates defenses to protect your health. Signs and symptoms of a reaction may include:

• Itchy skin
• Hives or rash
• Reaction at the injection site, such as pain or swelling
• Fever
• Chills
• Headache
• Difficulty breathing

In rare cases, MS treatments can trigger a severe allergic reaction called anaphylaxis, which is a medical emergency. Signs and symptoms of anaphylaxis include:

• Rash or hives
• Constriction of the airways or throat
• Chest tightness
• Vomiting or diarrhea
• Dizziness or fainting

You may be given oral or IV diphenhydramine before your infusion if you’re taking one of the following disease-modifying therapies (DMTs):

• Alemtuzumab (Lemtrada)
• Natalizumab (Tysabri), sometimes after first using diphenhydramine
• Ocrelizumab (Ocrevus)
• Ublituximab-xiiy (Briumvi)

IV or subcutaneous (under the skin) immunoglobulin is a supportive treatment sometimes used to reduce symptoms of an MS flare. This therapy is also sometimes given with diphenhydramine.

Side Effects of Diphenhydramine

As with any medication, you may experience some side effects when using diphenhydramine. Drowsiness is a common side effect of diphenhydramine. Other common side effects include:

• Dry mouth
• Dry eyes
• Dizziness
• Stomach upset

Less commonly, diphenhydramine has been known to cause hyperactivity rather than the expected drowsiness. It’s impossible to predict which of these two effects a person will experience until they take the medication for the first time.

In rare cases, diphenhydramine can cause serious side effects or allergic reactions that require emergency medical attention. Symptoms include:

• Difficulty breathing
• Mouth or throat swelling
• Pounding heartbeat
• Trouble urinating
• Confusion

Some people with MS find that diphenhydramine helps prevent reactions, while others forgo it. “I take a Benadryl before my infusion and then halfway through, they have had to slow it down and give me another dose of Benadryl — my throat likes to itch and cough, but the extra Benadryl takes care of it all,” one MyMSTeam member wrote.

“I take a Benadryl before my infusion, and then halfway through, they have had to slow it down and give me another dose of Benadryl.”

— a MyMSTeam member

Another said, “They don’t give me Benadryl anymore. The Benadryl made me worthless for the entire day.”

If you find that any of the pretreatment medications — diphenhydramine or others — cause effects that you find unpleasant, talk to your neurologist about your options for switching treatments. There may be other effective treatment options that don’t affect your quality of life. You may also want to talk to your doctor about switching treatments if your MS symptoms are getting worse due to disease activity and damage to myelin, the protective sheath of nerve fibers in the central nervous system (CNS).

New Research on Antihistamines and Multiple Sclerosis

Although not related to the use of diphenhydramine with MS treatments, recent neurology research led by Ari Green and Jonah Chan at the University of California, San Francisco, has pointed to other promising benefits of antihistamines that could ultimately lead to new ways of treating MS.

A clinical trial (a study that tests a drug’s safety and effectiveness) with 50 participants discovered that clemastine, an OTC antihistamine, may lead to remyelination (myelin repair) in people with MS. This effect could potentially help heal lesions that cause nerve damage, according to the authors of the study.

However, this treatment approach hasn’t been approved by the U.S. Food and Drug Administration (FDA) yet. The authors emphasized that clemastine acts as a sedative, which is highly problematic for people with MS, who may have motor or balance problems, so it couldn’t be used at high doses. Research is still in the early stages.

If you have questions about the latest research on MS treatments, talk with your doctor.

Join the Conversation

On MyMSTeam, people share their experiences with multiple sclerosis, get advice, and find support from others who understand.

Has your doctor recommended using an antihistamine with your infusions or injections? Let others know in the comments below.