Does Trazodone Have Diphenhydramine? (3 Differences)

By Ivan Kahwa

Page last updated: 02/02/2024 | Next review date: 02/02/2026

Author bio

Mr Ivan Kahwa is a chemist and phytopharmaceutical scientist with expertise in chemistry, pharmacology, phytochemistry, and Nanobiotechnology. He writes and reviews content on these topics.

Mr Ivan Kahwa’s Highlights:

Guest Researcher at the University of Leipzig, Senior Research Fellow/Scientist, and Lecturer at the Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology.

Professional Experience:

Mr Ivan joined PHARMBIOTRAC as a research fellow/scientist during his master of science tenure. He contributed to the development of most of the phytopharmaceutical products in the project. Furthermore, he participated in carrying out the pharmacological activities of the developed products in laboratory animals such as mice and rats in order to develop proper doses hence leading to pre-clinical studies.

With the above relevant research experience, Ivan started to work with the University of Leipzig on collaborative projects with Mbarara University to develop the chemistry of Ugandan Medicinal plants and their pharmacological activities. This was coupled with several consultative positions by different German NGOs. Mr. Kahwa is also a supporting in the teaching and learning at the Departments of Pharmacy and Pharmaceutical Sciences, Faculty of Medicine, Mbarara University of Science and Technology.

With the increase in antimicrobial resistance globally, Ivan retooled his thinking towards developing new naturally derived antibiotic regimens from Ugandan propolis with the assistance of nanotechnology to improve their delivery to microbial cells. Kahwa has also published over 28 articles in peer-reviewed journals and he is currently reviewing for many journals.

Education:

2023-2027: PhD in Pharmaceutical Sciences (ongoing) with a focus on Pharmaceutical Microbiology and Nanobiology at Mbarara University of Science and Technology.

2022: 2Msc. in Pharmacognosy and Natural Medicine Science at Mbarara University of Science and Technology.

2018: Bachelor of Science (Chemistry) at Mbarara University of Science and Technology.

Publications:

▪ Iqbal, S., Jabeen, F., Kahwa, I., & Omara, T. 2023. Suberosin Alleviates Thiazolidinedione-Induced Cardiomyopathy in Diabetic Rats by Inhibiting Ferroptosis via Modulation of ACSL4-LPCAT3 and PI3K-AKT Signaling Pathways. Cardiovascular Toxicology. https://doi.org/10.1007/s12012-023-09804-7

▪ Gupta, A. K., Yadav, R., Sharma, S., Sawale, J., & Kahwa, I. 2023. Anti-ageing Activity and Antioxidant Activity of Methanol Extracts of Leaves and Flowers of Salvia officinalis and Rosmarinus officinalis. Journal of Young Pharmacists, 15(3), 448–455. https://doi.org/10.5530/jyp.2023.15.60

▪ Tolo, C.U., Kahwa, I., Nuwagira, U., Weisheit, A. and Ikiriza, H., 2023. Medicinal plants used in treatment of various diseases in the Rwenzori Region, Western Uganda. Ethnobotany Research and Applications, 25, pp.1-16.

https://ethnobotanyjournal.org/index.php/era/article/view/4683

▪ Kahwa, I., Ajayi, C.O., Yadav, R., Chauhan, N.S., Shah, K., Abdelgadir, A.A., Shegena, E.A., Daniel, S., Omara, T., Asiimwe, J.B. and Ikiriza, H., 2023. Pharmacognostic and phytochemical studies as an invaluable approach for correct identification of medicinal plants: The case of Artemisia vulgaris L. substituted for Artemisia annua L. in Western Uganda. TMR Integr Med, 7, p.e23004.

https://doi.org/10.53388/TMRIM202307004

▪ Nalimu, F., Oloro, J., Kahwa, I. and Ogwang, P.E., 2021. Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox. Future Journal of Pharmaceutical Sciences, 7, pp.1-21.

https://doi.org/10.1186/s43094-021-00296-2

▪ Elamin, O.H.S., Ali, M.A., Elgezuli, I.A.A., Bashir, M.A. and Kahwa, I., 2021. Diagnosis of pre-and post-treatment of echinococcus granulosus with counter current immune electrophoresis and bacterial co-agglutination. Journal of Microbiology and Infectious Diseases, 11(02), pp.88-94.

https://doi.org/10.5799/jmid.951600

Published book Chapter

▪ Kahwa, I., Ayesiga, I., Nakalema, S., Alinaiswe, R., Mbabazi, R. and Iqbal, S., 2023. Natural products in the management of onchocerciasis. In Natural Products in Vector-Borne Disease Management (pp. 63-80). Academic Press. Book Chapter.

https://doi.org/10.1016/B978-0-323-91942-5.00012-4

Submitted manuscripts Under Review:

▪ Comparison of the Wound Healing Activity of the Leaf and Leaf Ash Extracts of Vernonia amygdalina in Rats. Journal name: Clinical Phytoscience

▪ Ethnobotanical Survey of Medicinal plants used in the management of cancer in Uganda. Journal name: Journal of Herbal Medicine

▪ Ethnobotanical survey and phytochemical screening of medicinal plants used in treatment of epilepsy by PROMETRA-Uganda Traditional Health Practitioners in Mpigi District, Uganda. Journal name: Journal of Ethnopharmacology

Submitted book chapters under review

1.Book title: Algae as a Natural Solution for Water-Food-Energy Nexus, Section 4: Microalgae and cyanobacteria for food applications, Chapter 4.6: Safety, toxicological and allergenic aspects of using algae for food. Authors: Christine Kyarimpa, Tom Omute, Caroline K. Nakiguli, Alice V. Khanakwa4, Christopher Angiro, Ivan Kahwa, Fortunate Ahumuza, Timothy Omara*. Publisher: Springer Nature Singapore Pte Ltd. 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore.

2.Book title: Nutraceuticals Inspiring the Contemporary Therapy for Lifestyle Diseases. Chapter: Nutraceutical applications of Seaweeds and their Phytocompounds in Nutrition and Treatment of Diseases. Authors: Ivan Kahwa, Timothy Omara , Innocent Ayesiga , Gael Noel Neh Neba Ambe , Zehbanaz Javidbhai Panwala , Rachel Mbabazi , Shabnoor Iqbal , Christine Kyarimpa , Christine Betty Nagawa , Kamal Shah ,Nagendra Singh Chauhan* Publisher: CRC Press

You can view my works on the following professional sites:

Research Gate: https://www.researchgate.net/profile/Ivan-Kahwa

Google Scholar: https://scholar.google.com/citations?user=tOwrvqoAAAAJ&hl=en

ORCID: https://orcid.org/0000-0002-6440-3437

Linkedin: https://de.linkedin.com/in/ivan-kahwa-865450159

Ivan Kahwa

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In this article, we will discuss whether Trazodone contains diphenhydramine. We will also discuss some basic differences between the two medications.

Does Trazodone have diphenhydramine?

No, Trazodone does not contain diphenhydramine (Benadryl). Both are different medications used for different purposes.

Trazodone is a serotonin antagonist and reuptake inhibitor (SARI) and an antidepressant. It is an FDA-approved medication for major depressive disorder (MDD) (1).

Diphenhydramine is a first-generation antihistamine available as an over-the-counter (OTC) medication for treating conditions like dystonia, insomnia, pruritis, urticaria, vertigo, and motion sickness (2).

Trazodone and diphenhydramine are entirely different medications. They differ in their mechanism of action, indications, side effects and contraindications.

How does Trazodone differ from diphenhydramine?

Trazodone and diphenhydramine differ in the following aspects:

Mechanism of action

Trazodone is a SARI and it works by blocking the reuptake of serotonin which increases serotonin levels in the body. It also acts as an antagonist of some serotonin receptors and histamine (H1) and alpha-1 adrenergic receptors (3).

Due to its effects on serotonin, Trazodone has antidepressant activity. As it blocks different receptors, it also has a sedative action in low doses.

Benadryl, on the other hand, is an antihistamine which shows its effects by attaching to H1-receptors and preventing histamine from binding to it. Histamine is a chemical substance seen in an allergic reaction and is known for causing symptoms of allergy such as runny nose, watery eyes etc (2).

Diphenhydramine also produces sedation and is sometimes used to induce sleep during allergic reactions.

Therapeutic indications

Trazodone is an FDA-approved drug for major depressive disorder (MDD). It is also used off-label for the following conditions (3):

Insomnia
Anxiety
Fibromyalgia
Bulimia
Substance abuse

Diphenhydramine, on the other hand, is used for the following therapeutic indications (2):

Insomnia
Allergy
Pruritis
Urticaria
Vertigo

Side effects

Commonly reported side effects of Trazodone include (4):

Headache
Dry mouth
Fatigue
Blurred vision
Dizziness
Constipation
Drowsiness
QT prolongation
Acid reflux
Decreased concentration
Suicidal thoughts
Visual hallucinations
Orthostatic hypotension

Side effects of diphenhydramine include (5):

Sedation
Dizziness/lightheadedness
Urinary retention
Increased heart rate
Constipation
Blurred vision

Can you use Trazodone and diphenhydramine together?

Trazodone and diphenhydramine combination should only be used under medical supervision. Although these two meds don’t chemically interfere with one another, they can cause some similar side effects, which is the main reason why their combination is usually avoided.

Both Trazodone and diphenhydramine are sedative medications, and taking them together can increase the risk of excessive sedation. This can lead to dizziness, confusion, and impaired motor coordination.

Their combination can also increase the risk of respiratory depression, which is a potentially life-threatening condition characterized by slow, shallow breathing.

Trazodone and diphenhydramine can also cause cognitive impairment, including drowsiness, confusion and difficulty concentrating when taken alone. Combining these medications can further increase the risk of impaired cognition, which can affect their daily life activities.

Combining these medications increases the risk of side effects including allergic reactions gastrointestinal upset and cardiac arrhythmias.

What are alternatives to diphenhydramine while taking Trazodone?

If you are taking Trazodone and need an alternative to diphenhydramine for allergy or cold relief, there are several options that are generally considered safe to use with Trazodone. These include:

Second generation antihistamines

Medications like loratadine, cetirizine and fexofenadine are considered safer options to manage allergy symptoms without causing significant drowsiness.

Nasal corticosteroids

Nasal sprays like Flonase and triamcinolone can be used for nasal allergy symptoms. These sprays do not get absorbed in systemic circulation as oral medications do. This reduces the chances of adverse events.

Decongestants

OTC decongestants like pseudoephedrine can help with nasal congestion, but it is essential to use them cautiously and consult your healthcare provider, as they may increase blood pressure.

Natural remedies

Natural remedies like honey water, steam inhalation, or herbal supplements like butterbur or quercetin may provide relief from allergy symptoms. However, talk to your healthcare provider before taking any herbal supplements to avoid potential interactions.

In my opinion, Trazodone and diphenhydramine are distinct medications with different mechanisms of action and purposes. While both medications can cause drowsiness and sedation, they are not the same drug, nor do they contain each other as active ingredients.

I suggest using them as prescribed and directed by a healthcare professional to achieve their intended therapeutic effects and avoid potential adverse reactions.