There is considerable risk of physical harm when combining these substances. Use extreme caution.
Note: There is a significant risk of seizures from this combination. The combination is likely to increase each other’s negative side effects, such as nausea, dizziness, and loss of consciousness. At higher dosages, pregabalin is likely to increase diphenhydramine’s deliriant effects, inhibition, and risk of injury. Medical dosages are not reported to be a concern.
Substances in these categories
Diphenhydramine
Pregabalin
Sources
- Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.” — Altair. (n.d.-a)
- Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863. — Barker-Haliski, M., & White, H. S. (2015)
- Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18. — Ben-Menachem, E. (2004)
- Diphenhydramine overdose — Medline Plus Medical Encyclopedia (2023)
- Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.” — Douke, R. (n.d.)
- Comparison of the effects of pregabalin and famotidine with pregabalin and diphenhydramine on postoperative abdominal pain. International Journal of Surgery Open, 58, 100674. — Fakhr, M. S., Motamed Chaboki, P., Ashayeri, H., Sahranavard, P., Mohammadipanah, S., & Zamanabadi, M. N. (2023)
- Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597. — French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)
- Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398. — Gayatri, N. A., & Livingston, J. H. (2006)
- Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154. — Hitchings, A. W. (2016)
- Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440. — Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)
- Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose. Clinical Toxicology, 48(9), 945–948. — Jang, D. H., Manini, A. F., Trueger, N. S., Duque, D., Nestor, N. B., Nelson, L. S., & Hoffman, R. S. (2010)
- Antihistamines as a common cause of new-onset seizures: a single-center observational study. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(6), 2505–2508. — Kim, H., Kim, S. H., & Kim, J. B. (2021)
- Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561. — Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)
- Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397. — Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)
- Pregabalin - Erowid Exp - “Stay Away.” — Sean. (n.d.-b)
- Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20. — Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)
- Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130. — Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)
Interaction Matrix
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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.