Does trazodone increase bleeding risk? (3+ cautions)

In this article, we will discuss whether trazodone can increase the risk of bleeding, what research suggests, what factors can contribute to trazodone-induced bleeding risk, and what to do if you are concerned about increased bleeding with trazodone use.

Does trazodone increase bleeding risk?

Yes, trazodone can increase the risk of bleeding in individuals using it for the treatment of depressive disorders. Trazodone is generally considered safe for use, but it has a tendency to increase the risk of bleeding, especially when used in combination with drugs that affect blood clotting. (1)

Trazodone belongs to the class of drugs known as serotonin modulators, which affect the balance of serotonin in the brain. It is an FDA-approved drug for the treatment of major depressive disorders, but it can also be used to treat sleep problems. (2)

However, individual responses to trazodone can differ, and not everyone will experience an increased risk of bleeding.

How does trazodone increase the risk of bleeding?

Trazodone’s tendency to increase bleeding risk is believed to be related to an increase in serotonin levels in the synaptic cleft of the brain. Trazodone increases serotonin levels by inhibiting serotonin transporter and serotonin type-2 receptors and interferes with platelet function and coagulation pathway.

The risk of bleeding increases with the concomitant use of NSAIDs, warfarin, and other anticoagulant drugs. (2)

What does research suggest?

Research on the bleeding risk with the use of trazodone, a serotonergic antidepressant, suggests that trazodone is among those antidepressants that have the highest risk of gastrointestinal bleeding, and with the concomitant use of NSAIDs, this risk increases by many folds. (3)

Another study was done on orthopaedic patients who had hip replacement surgery; 66 patients used serotonergic antidepressants, 29 patients used nonserotonergic antidepressants, and 285 patients were in the reference group. The study concludes that the group of patients on serotonergic antidepressants had significantly higher blood loss during the procedure. (4)

A nonsystemic review of the bleeding risk with antidepressants concluded that the drugs with the serotonin inhibition mechanism increase the bleeding risk by 1.16- to 2.36-fold, and by using the NSAIDs with these drugs, this risk increases by 3.17-10.9-fold. (5)

Another study suggested that the combination of NSAIDs and trazodone can cause intracranial hemorrhage (ICH). Trazodone alone can also cause ICH in patients using it to treat their mental health conditions. (6)

What factors can contribute to increased bleeding risk with trazodone?

Several factors may contribute to the risk of bleeding in individuals using trazodone to treat their mental health conditions. These include:

  • Drug interaction: Trazodone may interact with other medications and increase the risk of bleeding. These drugs are nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, warfarin, and other antiplatelet drugs. (1)


  • Age: Age can factor into increasing the bleeding risk with trazodone. Geriatrics are more susceptible to bleeding with the use of trazodone. (7)


  • Underlying health conditions: Patients with underlying conditions, such as bleeding disorders, liver disease, and stomach ulcers, may be more susceptible to the risk of bleeding with trazodone use.


  • Individual variability: Individual responses to trazodone can differ. Genetic and metabolic variabilities can also play a role and increase bleeding risk in people using trazodone.


  • Dosage and duration of use: Higher doses of trazodone and long-term use may contribute to an elevated risk of bleeding. It is crucial for healthcare providers to assess the appropriate dosage for each patient and carefully monitor them to avoid any unwanted symptoms.

What to do if bleeding risk with trazodone concerns you?

If you are using trazodone and are concerned about the potential risk of bleeding, it is crucial to discuss your concerns with your healthcare provider. Inform your doctor about all the medications, supplements, or OTC drugs to avoid potential interactions that may cause an emergency situation.

Your doctor can consider these options:

  • Lower your dosage: Your doctor might consider lowering the dose, as high doses can increase the risk of bleeding.
  • Treat underlying conditions: Your healthcare provider might advise you to get treatment for underlying health conditions that may increase the risk of bleeding.
  • Switch to an alternative: Your doctor might consider switching you to other antidepressants that have a different side effect profile than trazodone. e.g., agomelatine, bupropion, mirtazapine, etc.
  • Close monitoring: Your doctor will closely monitor you for signs of bleeding if you are in a high-risk group.

Your doctor will provide you with guidance according to your needs to make treatment more comfortable for you.


According to my knowledge and research on the topic, trazodone can increase bleeding risk in patients using it for major depressive disorders and insomnia. It is crucial for individuals using this medication to be on the lookout for any concerning signs and communicate openly with their healthcare providers.

Understanding the potential risk factors and taking precautions can help ensure the safe and effective use of trazodone in the management of depression and anxiety disorders.


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Trazodone, a prescribing guide by The U.S. Food and Drug Administration, Available from:


Shin JJ, Saadabadi A. Trazodone. [Updated 2022 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


Wan Po, A. L. (1999). Antidepressants and upper gastrointestinal bleeding: New results suggest a link. BMJ : British Medical Journal, 319(7217), 1081-1082.


Van Haelst IM, Egberts TC, Doodeman HJ, Traast HS, Burger BJ, Kalkman CJ, Van Klei WA. Use of serotonergic antidepressants and bleeding risk in orthopedic patients. The Journal of the American Society of Anesthesiologists. 2010 Mar 1;112(3):631-6.


Bixby, A. L., VandenBerg, A., & Bostwick, J. R. (2018). Clinical Management of Bleeding Risk With Antidepressants. Annals of Pharmacotherapy.


Hou, C., Lin, J., Lin, Y., Hwang, J., & Wang, C. (2020). Risk of Intracranial Hemorrhage With Concomitant Use of Antidepressants and Nonsteroidal Anti-inflammatory Drugs: A Nested Case-Control Study. Annals of Pharmacotherapy.


Wysokiński Adam, Margulska Aleksandra and Sobów Tomasz, Bleeding Complications in the Course of Treatment with Antidepressants in Elderly Patients, Current Psychiatry Reviews 2015; 11 (4) .

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