Urticaria
In a similar vein to anaphylaxis and allergic reactions, international guidelines have recommended the use of second-generation antihistamines over diphenhydramine and other first-generation antihistamines for over two decades.5,6 The initial treatment for urticaria, these guidelines urge, is a second-generation antihistamine. If the initial treatment isn’t successful, the guidelines recommend up-dosing the second-generation antihistamine to four times the daily dose (e.g., 40 mg of cetirizine daily rather than the standard daily dose of 10 mg), even before the addition of steroids.7 Use of diphenhydramine does not allow for this updosing for persistent urticaria.
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ACEP Now: Vol 41 – No 07 – July 2022Headaches
Diphenhydramine has historically been a common adjunct to migraine cocktails. Some administer diphenhydramine to reduce pain, relying on the purported role of histamine in migraine pathophysiology. Others add diphenhydramine to migraine cocktails to prevent adverse events such as akathisia from simultaneous medications such as metoclopramide or prochlorperazine. In 2016, however, Friedman et al., published a randomized controlled trial demonstrating that in adult patients with migraine headaches, the addition of diphenhydramine to 10 mg of metoclopramide did not result in greater improvement in pain scores, sustained headache freedom, or desire for the same medication again.8 Although this study was not designed to examine akathisia as a primary outcome, diphenhydramine did not reduce the incidence of akathisia, one of the other reasons given to add the medication to migraine cocktails. However, the risk of akathisia varies in studies. Another randomized trial found a whopping one in three patients given prochlorperazine 10 mg IV over two minutes developed akathisia compared with only 14 percent among those who received diphenhydramine.9 The incidence of extrapyramidal symptoms such as akathisia varies widely in headache studies, probably explained by the dose, type, and rate of medication administered. As such, emergency physicians can choose medications and doses less likely to be associated with extrapyramidal side effects (e.g., low dose haloperidol, droperidol, or metoclopramide) or longer infusion times (e.g., a 15-minute infusion). Additionally, like ketamine emergence reactions, which occur on occasion and can be mitigated to an extent by manipulating dosing, environment, and rate of administration, emergency physicians can be prepared to treat extrapyramidal side effects should they occur.
Sleep Aid
Oftentimes, the discussion around diphenhydramine turns to sleep. As discussed, first-generation antihistamines including diphenhydramine are sedating. However, this does not translate into improved sleep quality, because the medications increase the time to onset of rapid eye movement (REM) sleep and reduce the duration of REM sleep.10
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6 Responses to “The Death of Diphenhydramine”
July 17, 2022
Michael BernsteinI am in agreement with almost all of this. However, and strictly from personal and anecdotal experience, I still feel it is efficacious as an adjunct in the “migraine cocktail”. I use 12.5 mg IV (with Regaln and Toradol) in those with significant nausea, as I think it’s antiemetic properties help. Additionally, I think it’s sedative properties help in the agitated patient that I am giving Haldol and Ativan to. I am trying to switch to atypical antipsychotics or Ketamine when I can, but still occasionally reach for the old B52 if it’s my only choice. I guess now, with the lack of availability of Ativan it would be B55 with Midazolam….In these two instances I feel that the risk/benefit profile favors the potential benefit.
July 17, 2022
Charlene DoyleRegarding benadryl for migraine – sleep is usually the true treatment for migraine. Unfortunately it is difficult to achieve with a migraine but quite easy with benadryl. Also, who has access to droperidol, one of my favorite medications.
July 17, 2022
Misty Navarro GreensonI have been adding 12.5 mg of Benadryl to my migraine cocktail for 20 years and have never had any issues. I don’t have a lot of patients with akisthesia and when I have an extra 12.5 has relieved these symptoms. I don’t see the evidence for this sweeping statement. Please educate me.
September 1, 2022
Louise B AndrewI too would never bury Benadryl. I well remember our collective professional relief when the Phenergan-Reglan-Benadryl cocktail freed us from having to use narcotics for migraines… and it had about a 99% success rate. The Benadryl probably prevented dystonic reactions, and if it caused drowsiness, well, YES, that helps greatly to break the cycle of a migraine. As a migraineur, I used this on myself (not on duty of course) and just don’t believe this is any less safe than any of the other formulations mentioned.
What are you doing for dystonic reactions incidentally? Some expensive new drug?
September 4, 2022
JSWBenadryl isn’t going anywhere. Because I can’t remember the last time is caused any serious adverse effects clinically in the ED. Cool story though.
September 10, 2022
W. Anthony GerardThank you, Dr. Westhafer for this interesting article. I think you appropriately challenge all of us to be cautious when we use Diphenhydramine.
But maybe your title, and your premise, should be asked as a question, instead of stated as an imperative? ( Ie, Is this the Death of Diphenhydramine?)
I agree with the other physicians who commented above. I would like to see evidence, or a more detailed discussion, of the use of Benadryl for migraines in combination with Compazine.
How about as a local anesthetic when pts are allergic to lidocaine? There are other indications for this medication that weren’t discussed, and should be, before we drop it’s use.
Finally, I don’t think you looked at the evidence suggesting that sedation could be a benefit, rather than risk, in many patients with urticaria and pruritis?
Second and third generation antihistamines work rapidly and have less sedation, but there is still an indication for First generation antihistamines ( diphenhydramine) in patients who with “severe” pruritis – at least q hs.
There is an evidence-based review of the efficacy of antihistamines in relieving pruritus from atopic dermatitis ( AT) published in Arch Dermatol 1999;135:1522–5. It’s been challenged recently by other studies of AT.
I don’t know of any evidence outside the derm literature comparing First and Second generation anti-histamines for other causes of pruritis, but I still use Bendadryl for severe itching in patients with pruritis at least at bedtime. And that’s what I’m taking if I ever get severe
rhus dermatitis.
Maybe one of our EBM or pharmacology colleagues can give us more information about these issue in a follow -up article?