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Trazodone: Side effects, interactions, and overdose

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The bottom line

Trazodone is a prescription oral selective serotonin reuptake inhibitor used for treatment of major depressive disorder and other conditions including anxiety and sleep disorders. Common trazodone brands names include Desyrel and Desyrel Dividose. Trazodone interacts with certain medications and alcohol and should be taken only as prescribed.

Prevention Tips

  • Store all medications in a dry, safe place away from children and pets.

  • Take trazodone only as prescribed by your doctor.

  • To prevent drug interactions, talk with your pharmacist or doctor about any drug changes or use of over-the-counter medications or dietary supplements.

This Really Happened

A 40-year-old man ingested 2.2 grams (approximately 10 tablets) of trazodone. He became unconscious and developed difficulty breathing. His blood pressure was abnormally low, and his heart rate was irregular. He was placed on a ventilator and admitted to a cardiac intensive care unit until he became stable. He was discharged 8 days later following a psychiatric consultation. 

What is trazodone and what is it used for?

Trazodone (Desyrel) is an antidepressant that works on chemicals and chemical receptors in our bodies. Trazodone falls under a class of medications known as selective serotonin reuptake inhibitors (SSRIs) and is approved by the United States Food and Drug Administration as a treatment for major depressive disorder. Trazodone works by increasing the amount of serotonin within the brain. The increased levels of serotonin are believed to affect sleep, mood disorders, pain, and other conditions.

Is trazodone a controlled substance? 

Trazodone is not a narcotic or controlled substance. Trazodone is not considered to be an addictive substance when used as prescribed.

What are the side effects of trazodone? 

Common side effects of trazodone use include dry mouth, blurred vision, drowsiness, fatigue, vomiting, and dizziness. Trazodone may cause a decrease in blood pressure, especially in older adults and in people who stand up suddenly.  Standing up slowly from a sitting or recumbent position may lessen this effect. Men who take trazodone may experience painful and prolonged erections. This condition is known as “priapism”, and it requires immediate medical attention to prevent permanent tissue damage from occurring. Less common effects of trazodone can include irregular heartbeats, personality changes, and low blood sodium levels (also called “hyponatremia”). Antidepressants, including trazodone, may increase suicidal thoughts, especially in younger patients, during the first few months of drug therapy, and when a dosage is increased.

Trazodone Interactions

Taking trazodone with other medications that increase serotonin levels, such as dextromethorphan, tricyclic antidepressants, tryptophan or 5-HTP, and buspirone, can cause a potentially life-threatening condition called “serotonin syndrome”. Trazodone commonly causes drowsiness, which may be increased when taken with other sedating medications. People with underlying heart disease, or those who take medications that affect heart rhythm, are at increased risk of developing irregular heartbeats when taking trazodone.

Can trazodone be taken with alcohol? 

Trazodone may increase the sedating effects of alcohol, and taking trazodone with alcohol can lead to excessive somnolence or confusion. Because of this, it is recommended to avoid drinking alcohol while taking trazodone.

Can I take melatonin with trazodone for sleep?

There are no known interactions between trazodone and melatonin, however taking both together may cause excessive sedation. In addition, melatonin products may contain unwanted contaminants that can interact significantly with trazodone. In one study, 8 out of 31 melatonin supplement products tested contained 5-HTP, a serotonin precursor that was not listed on the product label.  Taking these contaminated melatonin products together with trazodone may increase the risk of serotonin syndrome.

Is it safe to take trazodone during pregnancy?

There are currently no well-controlled published studies of trazodone use by pregnant women, however, some animal studies show an association between trazodone use and fetal harm. Because of this, pregnant women should carefully discuss the risks and benefits of trazodone use with their physicians. The National Pregnancy Registry for Antidepressants (NPRAD) is dedicated to evaluating the safety of antidepressant medications that are taken during pregnancy. Women who take trazodone during pregnancy are encouraged to participate in this study in order to help scientists and doctors learn more about the effects of this drug on fetal outcomes. Learn more about the registry.

Are there any symptoms of trazodone withdrawal? 

Symptoms of trazodone withdrawal, including adverse reactions, may occur upon abrupt discontinuation of this drug. To avoid trazodone withdrawal, it is important to gradually reduce the dose of trazodone rather than stopping the drug suddenly. Symptoms of withdrawal may include rapid mood swings, irritability, and anxiety. Since the signs and symptoms of trazodone withdrawal can be very uncomfortable, it is important to gradually decrease the dose of trazodone under the guidance of a physician.

Can you overdose on trazodone? 

Trazodone overdose can occur when a person takes too much trazodone at one time. Signs and symptoms of an overdose may include excessive drowsiness, low blood pressure, fainting, or an irregular heartbeat.

When trazodone is taken with other medications that affect serotonin levels, a severe and sometimes fatal condition called serotonin syndrome may occur. Serotonin syndrome can occur in individuals who take trazodone at the prescribed dose as well as in overdose. Signs and symptoms of serotonin syndrome can include confusion, muscle tremors or stiffness, and changes in blood pressure or heart rate.

What to do if someone takes too much trazodone or takes it by accident 

If someone takes too much trazodone or takes it by mistake, use the webPOISONCONTROL® online tool to get help, or call your poison center at 1-800-222-1222. Whether online or by phone, expert guidance is always free, confidential, and available 24 hours a day.

Desyrel® is manufactured by Pragma Pharmaceuticals, LLC and distributed by Fera Pharmaceuticals, LLC.

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Micaela E Seazzu, BS
Doctor of Pharmacy Student, Pharmacy Intern at the University of New Mexico

References

Shin JJ, Saadabadi A. Trazodone. [Updated 2022 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470560/

Young SN. How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci. 2007;32(6):394-399.

Schwasinger-Schmidt TE, Macaluso M. Other Antidepressants. Handb Exp Pharmacol. 2019;250:325-355. doi:10.1007/164_2018_167

Sub Laban T, Saadabadi A. Monoamine Oxidase Inhibitors (MAOI) [Updated 2022 Jul 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539848/

Bauer M, Severus E, Köhler S, Whybrow PC, Angst J, Möller HJ; WFSBP Task Force on Treatment Guidelines for Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders. Part 2: maintenance treatment of major depressive disorder-update 2015. World J Biol Psychiatry. 2015;16(2):76-95. doi:10.3109/15622975.2014.1001786

Husak N, Leonard JB, Seung H, Klein-Schwartz W. Single-substance trazodone exposures reported to US poison centers from 2000 to 2019. Clin Toxicol (Phila). 2022;60(9):1032-1038. doi:10.1080/15563650.2022.2068423

COG Committee on Practice Bulletins--Obstetrics. ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists Number 92, April 2008 (Replaces Practice Bulletin Number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008;111(4):1001-1020.

Hiemke C, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry. 2018;51(1-02):9-62. doi:10.1055/s-0043-116492

White WB, Wong SH. Rapid atrial fibrillation associated with trazodone hydrochloride. Arch Gen Psychiatry. 1985;42(4):424. doi:10.1001/archpsyc.1985.01790270114017

Warrington SJ, Ankier SI, Turner P. Evaluation of possible interactions between ethanol and trazodone or amitriptyline. Neuropsychobiology. 1986;15 Suppl 1:31-7.

Erland LA, Saxena PK. Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content. J Clin Sleep Med. 2017 Feb 15;13(2):275-281.

Desyrel Prescribing Information. Fera Pharmaceuticals, LLC. Locust Valley, New York. Revised June 2017.

Khouzam HR. A review of trazodone use in psychiatric and medical conditions. Postgrad Med. 2017 Jan;129(1):140-148.

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