Diphenhydramine

Diphenhydramine or diphenhydramine hydrochloride is a commonly used antihistamine, which is also used for coughs, to aid sleep, for certain symptoms of Parkinson's disease, as well as for allergy symptoms, bites, itching and eczema. Diphenhydramine is the active ingredient in Benadryl, which is sometimes used as a sleep aid as well as an anti-histamine.

Additional active ingredients
Many products containing diphenhydramine contain other ingredients, for example: Other common ingredients include:
 * acetaminophen (paracetamol) for night-time pain relief
 * expectorants like guaifenesin, or dextromethorphan hydrobromide in cough products
 * levopenthol, a decongestant and pain reliever
 * ethyl (a form of alcohol), especially used in cough syrups
 * lactose, which is common in many tablets
 * food colorings, especially reds and blues

Brand names
Diphenhydramine is marketed under many different brand names including:
 * Allermax
 * Banophen
 * Benadryl
 * Benylin Chesty Coughs Original and Benylin Mucus Cough Nights (syrup)
 * Compoz Nighttime Sleep Aid
 * Covonia Nighttime Forumla
 * Diphedryl or Diphenhis
 * Nytol One-A-Night
 * Nytol QuickCaps
 * QlearQuil Nightitme Allergy Relief
 * Siladryl Allergy
 * Silphen Cough
 * Sominex original
 * Tranquil
 * Twilite
 * Vanamine PD
 * Unisom Sleepgels maximum strength
 * Z-Sleep
 * ZzzQuil

Evidence
Clinical trials of the effects of diphenhydramine on ME/CFS patients have not been conducted.

Long COVID
Two female patients have been reported to have experienced rapid and significant improvements in their Long COVID symptoms after taking diphenhydramine, in particular in exercise tolerance and post-exertional malaise. The patients used doses of 50mg and 25mg of diphenhydramine respectively, with one of these patients also responding to 50mg hydroxyzine pamoate. These effects did not occur using fexofenadine. Pinto et al. (2022) stated that some COVID-19 patients had improved after antihistamine treatment, and according to Nathalie Lambert, long covid patients in a Survivor Corps social media group has frequently posted about antihistamines. Glynne et al. (2022) also commented on anecdoteal reports of long COVID patients improving with antihistamines, and the role of histamine in COVID-19. Glynne et al. conducted a small observational study using a combination of H1 (loratadine or fexofenadine) and H2 (famotidine or nizatidine histamine receptor antagonists (HRAs) for a minimum of 4 weeks, finding clinically significant improvement in the majority of patients.

Dosage
The usual dose suggested is:
 * creams for bites, itches or eczema - apply a thin layer once or twice a day
 * allergies and hayfever, itching or as an anti-histamine - 25mg to 25mg, 3 or 4 times a day
 * cough and cold symptoms – diphenhydramine is typically mixed with other medicines, the dose depends on the medicine
 * creams for bites, itches or eczema - apply a thin layer once or twice a day
 * sleep problems or insomnia - 25mg to 50mg

Risks and safety
Diphenhydramine has a wide range of side effects include dizziness and drowsiness (sedation), and is sometimes used for insomnia.

It is described as non-addictive/not habit forming, but recently concerns have been raised about long term use including the reduced effectiveness in the long term, causing people to increase the dose. Theoharides and Stewart (2016) stated that in high risk over 65s taking 50mg for 3 years or 50mg for 3 years was associated with cognitive dysfunction.

Using a product containing diphenhydramine marketed for nighttime pain, coughs or cold and flu also involves the side effects of other active ingredients, or from inactive ingredients such as food colorings.

Costs and availability
Diphenhydramine is available over the counter, under many different brand names including Benadryl. Diphenhydramine is available in tablet, capsule or syrup/liquid form, and in anti-histamine products as a cream, spray or ointment to be applied to the skin.

In the UK, diphenhydramine is a pharmacy-only medication and is not given on prescription. Diphenhydramine is available under the brand names Benylin Chesty Coughs, Histergan, and Nytol Once-A-Day.

Notable studies

 * 2022, Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines - (Full text)
 * 2022, Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection - (Full text)

Learn more

 * Diphenhydramine - drugs.com
 * Diphenhydramine - NHS
 * Diphenhydramine - WedMD