There is considerable risk of physical harm when combining these substances. Use extreme caution.
Note: There is a significant risk of serotonin syndrome with this combination. Monoamine oxidase A inhibitors may extend and increase the anticholinergic effects of DPH. The combination increases each other’s side effects, such as drowsiness, dizziness, dry mouth, and headaches. Medical dosages are not reported to be of concern.
Substances in these categories
Diphenhydramine
MAOIs
Sources
- Serotonin Reuptake Inhibition by Diphenhydramine and concomitant Linezolid use can result in Serotonin Syndrome Chest, 134(4), 4C. — Adawi Awdish, R. L., Whitmill, M., Coba, V., & Killu, K. (2008)
- Diphenhydramine: It is time to say a final goodbye. The World Allergy Organization Journal, 18(2), 101027. — Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)
- Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. Health Psychology Research, 10(4), 39576. — Edinoff, A. N., Swinford, C. R., Odisho, A. S., Burroughs, C. R., Stark, C. W., Raslan, W. A., Cornett, E. M., Kaye, A. M., & Kaye, A. D. (n.d.)
- Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434–441. — Gillman, P. K. (2005)
- Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus. — Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J. (2018)
- Anticholinergic Drugs in Geriatric Psychopharmacology. Frontiers in Neuroscience, 13, 1309. — López-Álvarez, J., Sevilla-Llewellyn-Jones, J., & Agüera-Ortiz, L. (2019)
- Monoamine Oxidase Inhibitors (MAOI). In StatPearls. StatPearls Publishing. — Sub Laban, T., & Saadabadi, A. (2025)
Interaction Matrix
Tap or hover on any cell to see the interaction. Click to view details.
These drugs work together to cause an effect greater than the sum of its parts. They aren't likely to cause an adverse or undesirable reaction when used carefully.
Effects are additive. The combination is unlikely to cause any adverse or undesirable reaction beyond those that might ordinarily be expected from these drugs.
One substance may reduce or counteract some of the effects of the other.
These combinations are not usually physically harmful, but may produce undesirable effects. Use caution.
There is considerable risk of physical harm when combining these substances. Use extreme caution.
These combinations are considered dangerous and should be avoided.
The interactions between these substances are not well documented.