Does trazodone alone cause serotonin syndrome? (3+ cautions)
By
Ivan Kahwa
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
In this article, we will discuss whether using trazodone alone causes serotonin syndrome, what are the symptoms of serotonin syndrome, what research suggests, what factors can contribute to serotonin syndrome caused by trazodone, and what to do if you experience this side effect.
Does trazodone alone cause serotonin syndrome?
Yes, trazodone can cause serotonin syndrome when used in higher or more frequent doses. Trazodone is an antidepressant that belongs to the serotonin antagonist and reuptake inhibitor (SARI) class. It works by increasing serotonin levels in the brain and helps treat depression. (1)
Trazodone has a tendency to cause serotonin syndrome in individuals who have been using it for a long time or taking higher doses. It is a life-threatening condition that occurs when the levels of serotonin are increased in the brain. (2,3)
It is an FDA-approved drug to treat major depressive disorders, and its non-FDA-approved use includes the treatment of insomnia. (1)
What are the symptoms of serotonin syndrome?
Serotonin syndrome can manifest with a variety of symptoms, including: (2,3)
- Agitation
- Rapid heartbeat
- Elevated blood pressure
- Dilated pupils
- Hallucinations
- Altered mental state
- Dizziness
- Flushing
- Sweating
- Tremors
- Restlessness
- Shivering and muscle twitching
- Incoordination and difficulty walking
- Nausea
- Vomiting
- Diarrhea
How does trazodone cause serotonin syndrome?
Trazodone causes serotonin syndrome by increasing the levels of serotonin in the synaptic cleft. It mainly inhibits the serotonin transporter and acts as an antagonist of serotonin type-2 receptors. (1,2) Trazodone can also cause serotonin syndrome by interacting with other medications or by concomitant use of serotonergic drugs, e.g., Citalopram. (3)
Several factors can contribute to the serotonin syndrome caused by trazodone. However, individual responses to medication can vary, so if you experience any of the above symptoms, talk to your healthcare provider.
What does research suggest?
Serotonin syndrome is mainly caused by serotonergic drugs, either alone or in combination. Trazodone is capable of causing mild serotonin syndrome as a side effect when used alone in therapeutic doses. (3,4,)
A case of serotonin syndrome was reported in 2015 in the Case Reports of Gastroenterology; the patient was taking trazodone and duloxetine at home and was given fentanyl following a liver biopsy. (5)
Research on trazodone-induced serotonin syndrome is limited. While studies and case reports suggest a potential link between trazodone and serotonin syndrome, the incidence of serotonin syndrome with trazodone is low. However, caution is still warranted, especially when trazodone is used in conjunction with other medications.
What are the diagnostic criteria for serotonin syndrome?
Serotonin syndrome can be fatal, so it’s essential to know when serotonergic side effects at therapeutic doses become serotonin toxicity. The diagnostic criteria include the following: (4,6)
- Spontaneous clonus
- Inducible clonus or ocular clonus
- Agitation
- Hyperthermia
- Tremors
- Hypertonia
- Hyperreflexia
What factors can contribute to serotonin syndrome when using trazodone alone?
Several factors can contribute to the development of serotonin syndrome in individuals taking trazodone alone:
- Dosage: Trazodone can cause serotonin syndrome in therapeutic doses, but the risk is increased by several folds when higher doses of trazodone are administered. (8)
- Individual variability: Variations in how the body metabolizes trazodone can also increase the risk of serotonin syndrome. Genetics can also play a role.
- Pre-existing conditions: Individuals with certain mental conditions, which can alter the levels of neurotransmitters in the brain or the metabolism of drugs, may be more susceptible to serotonin syndrome.
What to do if you experience serotonin syndrome?
Consult your healthcare provider regarding any unwanted symptoms that you are experiencing. Your doctor might lower the dose to alleviate the symptoms if they are mild. If you suspect you are experiencing serotonin syndrome while taking trazodone, it is crucial to seek immediate medical attention. Your doctor might follow these strategies to manage your symptoms. (4,10)
- Discontinuing trazodone: Discontinuation of trazodone may be necessary. Your doctor might consider discontinuing the causative agent if your symptoms are severe.
- Antidote: In severe cases of serotonin syndrome, when supportive care and sedation fail, cyproheptadine is used as an antidote to reduce the symptoms. (9)
- Sedation: The severity of your symptoms may demand sedation by using benzodiazepines, e.g., lorazepam or diazepam.
From my perspective, the risk of serotonin syndrome with trazodone alone is low so it is essential to report any unwanted symptoms to your healthcare provider so that adjustments can be made to your treatment plan.
Open communication with your healthcare provider, awareness of potential symptoms, and immediate medical attention are key components of ensuring the safe and effective use of trazodone.
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References
1.-
Shin JJ, Saadabadi A. Trazodone. [Updated 2022 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470560/
2.-
Simon LV, Keenaghan M. Serotonin Syndrome. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482377/
3.-
Trazodone hydrochloride, a prescribing guide by The U.S. Food and Drug Administration, Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018207s032lbl.pdf
4.-
Serotonin syndrome (serotonin toxicity), Serotonin syndrome (serotonin toxicity), Edward W Boyer, MD, PhD, Erica L Liebelt MD, FACMT, Michael Ganetsky, MD, Available from: https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity/print
5.-
Gaffney, R. R., & Schreibman, I. R. (2015). Serotonin Syndrome in a Patient on Trazodone and Duloxetine Who Received Fentanyl following a Percutaneous Liver Biopsy. Case Reports in Gastroenterology, 9(2), 132-136. https://doi.org/10.1159/000382069
6.-
Volpi-Abadie, J., Kaye, A. M., & Kaye, A. D. (2012). Serotonin Syndrome. The Ochsner Journal, 13(4), 533-540. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
7.-
Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf. 2008 Sep;7(5):587-96. doi: 10.1517/14740338.7.5.587. PMID: 18759711. https://pubmed.ncbi.nlm.nih.gov/18759711/
8.-
Gillman PK. Serotonin syndrome: history and risk. Fundam Clin Pharmacol. 1998;12(5):482-91. doi: 10.1111/j.1472-8206.1998.tb00976.x. PMID: 9794145. https://pubmed.ncbi.nlm.nih.gov/9794145/
9.-
Gillman, P. K. (1999). The serotonin syndrome and its treatment. Journal of Psychopharmacology. https://doi.org/10.1177/026988119901300111
10.-
Volpi-Abadie, J., Kaye, A. M., & Kaye, A. D. (2012). Serotonin Syndrome. The Ochsner Journal, 13(4), 533-540. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
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