If you migraine requires injectable medicines, decline intravenous Benadryl

Hopefully, your doctor has given you many treatment options, so that you can manage even the most severe attacks at home (including Compazine or Phenergan anti-nausea suppositories for when you are very nauseated or vomit and Imitrex or sumatriptan injection pen for severe pain). However, many people end up in an ER, where they are usually given an injection or intravenous medications. Unfortunately, there is no standard protocol for the best way to treat an acute migraine that does not respond to oral medications. Ideally, the first step should be an infusion of magnesium, which can provide fast relief for up to 50% of patients. Some ER doctors give an injection of sumatriptan or a non-narcotic pain killer ketorolac (Toradol). Others will give a nausea drug which can also help pain such as metoclopramide (Reglan) or prochlorperazine (Compazine). An allergy medicine, diphenhydramine (Benadryl) is also a popular choice.

A study by Dr. Benjamin Friedman and his colleagues at the Albert Einstein COllege of Medicine in the Bronx compared the efficacy of intravenous Reglan combined with Benadryl and Reglan without Benadryl. This was a double-blind study, meaning that neither the doctor giving the medicine nor the patient knew what was being given. They recruited 208 patients, which is a high enough number to produce reliable results. And the results showed that Reglan without Benadryl provided as much relief as with Benadryl.

Benadryl is not a dangerous drug, but can make you drowsy, so if you can, ask the doctor not to give it to you. It is not easy to tell a doctor what to do, especially during a severe migraine attack. But if doctor is agreeable, ask for intravenous magnesium followed by either sumatriptan or ketorolac injection as well as metoclopramide for nausea.

15 comments
  1. Dr. Mauskop says: 08/25/20212:12 pm

    You can go back to the ER for a shot of Benadryl.

  2. Kim bale says: 08/25/20211:02 pm

    ER gave me Ragland and Toridol cocktail for migraine. I can’t sit still and feel like my heart going to jump out of my chest but I’m so tired and I can’t stop crying . Called ER who said take Benadryl but it’s not working . What else can I do ?

  3. Dr. Mauskop says: 01/16/202110:05 pm

    Reglan is responsible for this extremely unpleasant side effect. The next time I would ask for Zofran instead.

  4. Dana says: 01/16/20211:26 am

    So a couple of times they have given me this cocktail; reglan ketorolac, & Solu-Medrol. And every time it’s like I fall asleep because it knocks me out and 30ish minutes after getting it I wake up feeling like I need to get out of there, and like I’m crawling out of my skin, the last time I paced around the bed until someone can in and asked for something to stop the feeling. I hate getting that drug it makes me feel like I’m going crazy.

  5. Dr. Mauskop says: 11/05/20208:33 pm

    You may want to ask for magnesium first, then, Toradol and after that, if her blood pressure is high, a blood pressure medicine, intravenously.

  6. George Bustamante says: 11/05/20202:52 pm

    Hello everyone, First and foremost I pray that all who suffer from migraines that one day you’ll get the real help that you need.Now I dont suffer from migraines my wife does she suffers from complex migraines. She has had 9 strokes and 1heart attack.Now when she is having an migraine and her blood pressure is going into the 200,she has tried almost every migraine medication there is and she has had side effects to all.So they give her norco 10/325 and 2mg dilated I’m not sure that’s the correct spelling but I’m sure you know what I’m trying to say. So now when I take her to the ER they ask what works for you to take the pain away and bring down your blood pressure. I’ll tell them 2mg dilated and they say oh no so they want to give her reglan and benadryl. But that puts her to sleep and when she wakes up her migraine is worse than when we got to the ER.If you are getting the same treatment please email me.

  7. Dr. Mauskop says: 08/12/20199:59 pm

    Reglan (metoclopramide) is known to cause such a reaction with severe restlessness, feeling of wanting to get out of one’s skin, and extreme discomfort. If you have such a reaction to Reglan, a similar or even worse reaction can occur from Compazine (prochlorperazine), which is also given for nausea and vomiting of migraine. The treatment of such a reaction is Benadryl, which can be also taken in a pill you buy over-the-counter, but the shot is faster and is more effective.

  8. Deanna says: 08/12/20199:45 pm

    I was in the hospital today for a migraine and they gave me Reglan with benadryl and it made me crazy, I felt like my legs were going to climb out of themselves, my body felt 100 degrees and I wanted to rip the iv out and run down the hall. It was absolutely awful, the second dose was toradol and magnesium and that only took the edge off, they asked me if I wanted more pain medication and I said no, I just want to go home. My head still very dull and it’s evening now.

  9. Dr. Mauskop says: 06/26/20194:46 pm

    Benadryl can sometimes help probably because it sedates and possibly, because of an allergic component present in some people. Magnesium in a pill or powder form can upset the stomach and cause diarrhea, while intravenous magnesium, especially if given too fast, can sometimes make a person too hot and nauseous. Feeling awful from magnesium also suggests that you are not deficient in magnesium and there is no point in taking it.

  10. Mel says: 06/26/20194:24 pm

    Benadryl helps alleviate my migraines as well. I can’t take reglan, even with benadryl, it still makes me feel too jittery and weird. I take Benadryl at home to get rid of my migraines that just won’t go away with my triptan alone, or when I run out of triptans. I am curious to know why Benadryl would help alleviate some peoples migraines though. I will also note that there are times when absolutely nothing works to alleviate my migraines, not oral nor intravenous medication helps with some of them. Magnesium through an IV doesn’t help, it makes them worse for me and makes me feel awful. Even taking it as pill or powder, it makes me feel horrible.

  11. Robert says: 11/26/201810:52 am

    I use orally ingested Benadryl to treat migraines on my own when I can’t or don’t want to take a Triptan. There is no doubt in my mind that for me it is effective. And I dose according to the directions on the bottle purchased OTC. It definitely makes me sleepy, so I only do this if I am free to sleep and won’t be driving or doing anything that requires good presence of mind. I consider Benadryl to be a real life-saver when I’ve run out of my monthly Triptan allotment and I wish my doctor would have suggested it years ago. I only started using it after being treated with it in the ER for a migraine that wouldn’t respond to Triptans.

  12. Dr. Mauskop says: 11/22/20176:10 pm

    Yes, Reglan (metoclopramide) can occasionally cause restlessness and agitation, which can be prevented or alleviated by Benadryl (diphenhydramine). Benadryl by itself however, is ineffective. Many ERs always give these two drugs together. The downside is that patients often get sleepy, but it is better than having a migraine.

  13. D says: 11/22/20171:16 am

    The Benadryl is used to combat the negative side effects of the Reglan, and I can’t imagine taking it without Benadryl also.

  14. Dr. Mauskop says: 07/10/201510:06 am

    You have to take all studies, including this one, with a grain of salt. Just because a particular drug or treatment doesn’t work for most people, it doesn’t mean that it won’t work for a minority of patients. This can be explained by the fact that migraine is not a homogeneous disorder but rather a collection of similar conditions caused by different genetic mutations. We already know several dozen genes that predispose to migraine headaches and these genes vary widely in their type and function, which explains varied manifestations and response to treatment.

  15. Mindy says: 07/08/201511:05 am

    I am SO surprised by these findings! The 3x I have received IV Benadryl I can feel the relief almost instantly. Yes, it does make me drowsy & it requires me to have someone drive me home, but it’s the only IV drug I’ve ever had that stops the pain instantly w/o side effects except drowsiness. I’ve had DHE, imitrex, toradol, raglan, depakote, zofran…none of which helped instantly. This result is interesting tho!!

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