DIPHENHYDRAMINE 

What is diphenhydramine?

Diphenhydramine is an antihistamine used to relieve symptoms of allergies, hay fever, or a cold, such as red, itchy, or watery eyes, sneezing, runny nose, and cough. It can also prevent nausea and vomiting, motion sickness, and vertigo. Compared to other antihistamines, diphenhydramine is the most sedating and can help you fall asleep. It also has a shorter duration of action and may need to be taken every four to six hours as needed.

How can diphenhydramine help alleviate certain long COVID symptoms? 

Histamine is a chemical our immune system releases that causes our allergy symptoms. Cells in our body called mast cells release histamine, and in some patients after COVID, they may release too much, leading to some of the symptoms of long COVID. Long COVID is believed to be a state of prolonged hyper-inflammation that follows the infection. Because diphenhydramine can block histamine type 1 receptors, it has the potential to relieve certain long COVID symptoms and has been reported to improve fatigue and cognitive symptoms specifically.¹

What evidence supports diphenhydramine’s use for long COVID?

There has been extensive research on the use of antihistamines in general for long COVID. Unfortunately, no evidence directly supports diphenhydramine’s use for long COVID. Two case reports noted considerable improvement in fatigue, “brain fog” or ability to concentrate, abdominal pain, and loss of smell and taste with diphenhydramine 25 mg or 50 mg.¹ The addition of diphenhydramine to a combination of ibuprofen and cimetidine was also found to help treat adult respiratory distress syndrome (ARDS) in a porcine model; however, these results may not extend to humans.²  

What are some things to be aware of when taking diphenhydramine?

Diphenhydramine should be used sparingly in older adults. It can cause blurred vision, urinary retention, nausea, and constipation, which may be worsened with other medications. Avoid taking diphenhydramine during the day, as it can cause drowsiness. While diphenhydramine can help with insomnia, it should not be routinely taken for this purpose. 

References:

1)      Pinto MD, Lambert N, Downs CA, et al. Case Report: Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection. JNP. 2022; 18:335-338. doi: 10.1016/j.nurpra.2021.12.01

2)      Sielaff TD, Sugerman HJ, Tatum JL, Blocher CR. Successful treatment of adult respiratory distress syndrome by histamine and prostaglandin blockade in a porcine Pseudomonas model. Surgery. 1987 Aug;102(2):350-7. PMID: 3112984.