Which antidepressants can cause bleeding? A Pharmacological Review

October 10, 2025 •

3 min read

Studies show that patients taking Selective Serotonin Reuptake Inhibitors (SSRIs) are about 40% more likely to experience severe gastrointestinal bleeding. Understanding which antidepressants can cause bleeding is crucial for patient safety, especially when combined with other common medications.

Quick Summary

Certain antidepressants, particularly SSRIs and SNRIs, increase bleeding risk by interfering with platelet function. The risk is higher for specific drugs and is amplified by concurrent use of NSAIDs or anticoagulants.

Key Points

SSRIs and SNRIs: These are the primary antidepressant classes that increase bleeding risk by impairing platelet function.
Mechanism of Action: They block serotonin reuptake in platelets, depleting them of a chemical necessary for proper blood clotting.
High-Risk Drugs: Antidepressants with high serotonin transporter affinity, like fluoxetine, paroxetine, and sertraline, pose a greater risk.
NSAID Interaction: Combining SSRIs with NSAIDs (e.g., ibuprofen) dramatically increases the risk of gastrointestinal bleeding, in some cases by more than 15 times.
Other Risk Factors: Advanced age, a history of ulcers, and concurrent use of anticoagulants (like warfarin) or antiplatelet drugs (like aspirin) amplify the bleeding risk.
Management Strategy: For high-risk individuals, doctors may choose an antidepressant with low serotonin affinity (e.g., bupropion) or add a proton pump inhibitor (PPI) to protect the stomach.
Surgical bleeding: SSRI use is associated with an increased risk of bleeding during and after surgery, though discontinuing the medication must be weighed against mental health risks.

Understanding the Link Between Antidepressants and Bleeding

Antidepressants, while important for treating mental health conditions, can carry a risk of abnormal bleeding for some individuals. This effect is linked to how these medications influence serotonin levels throughout the body. Platelets, which are vital for blood clotting, rely on serotonin to function properly. By interfering with serotonin reuptake, some antidepressants can deplete the serotonin in platelets, hindering their ability to aggregate and form clots, thus increasing the likelihood of bleeding. The most frequently reported type of bleeding is in the upper gastrointestinal (GI) tract, although increased risks of bruising, nosebleeds, intracranial hemorrhage, and bleeding during surgery have also been noted.

The Primary Culprits: SSRIs and SNRIs

The antidepressant classes most commonly associated with an increased bleeding risk are Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs). The degree of risk is often related to how strongly the drug binds to the serotonin transporter (SERT).

SSRIs: This group is most often linked to bleeding issues. By blocking serotonin reuptake, SSRIs can significantly lower serotonin levels in platelets, impairing their ability to aid in hemostasis. Research indicates that SSRIs can roughly double the risk of upper GI bleeding. Antidepressants with a high affinity for the serotonin transporter, such as fluoxetine, paroxetine, and sertraline, are associated with a higher bleeding risk.
SNRIs: Similar to SSRIs, SNRIs also affect serotonin reuptake and can increase bleeding risk, though studies sometimes offer conflicting evidence compared to SSRIs. Some data suggests a potentially lower overall risk than SSRIs, while other research connects SNRI therapy to a higher GI bleeding risk in specific patient groups. Examples include venlafaxine and duloxetine.
Other Antidepressants: Generally, Tricyclic Antidepressants (TCAs) do not appear to increase bleeding risk, with the exception of clomipramine due to its potent serotonergic effects similar to SSRIs. Atypical antidepressants like mirtazapine and bupropion are thought to have a lower bleeding risk because they have a lower affinity for the serotonin transporter.

Comparison of Antidepressant Bleeding Risk

The potential for bleeding varies significantly among different antidepressants, largely depending on how they work and their affinity for the serotonin transporter (SERT).


Antidepressant Class	SERT Affinity	General Bleeding Risk	Examples
SSRIs	High to Intermediate	Higher	Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram
SNRIs	Intermediate	Moderate	Venlafaxine, Duloxetine
TCAs	Low (except Clomipramine)	Generally Low	Amitriptyline, Nortriptyline (Clomipramine is higher risk)
Atypical Antidepressants	Very Low / Negligible	Lowest	Bupropion, Mirtazapine

Major Risk Factors and Drug Interactions

The risk of bleeding from antidepressants can be significantly increased when combined with other factors and medications.

NSAIDs: A major interaction exists with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen. The combined use of SSRIs and NSAIDs can increase the risk of upper GI bleeding by more than 15 times compared to using neither medication.
Anticoagulants and Antiplatelets: Taking antidepressants alongside blood thinners like warfarin or antiplatelet drugs such as aspirin and clopidogrel also substantially raises the risk of bleeding.
Patient-Specific Factors: Additional risk factors include being older, having a history of GI bleeding or peptic ulcers, liver cirrhosis, and undergoing major surgery.

Managing the Risk

For patients at a higher risk of bleeding, healthcare providers may consider various management strategies. These could include opting for an antidepressant with a lower affinity for the serotonin transporter, such as bupropion or mirtazapine. When an SSRI is necessary, especially with an NSAID, co-prescribing a proton pump inhibitor (PPI) can help reduce stomach acid and lower the risk of GI bleeding. It is important for patients to inform their doctor of any unusual bleeding signs, like easy bruising, frequent nosebleeds, or blood in their stool or vomit. The decision to stop an SSRI before surgery requires careful consideration of both bleeding risk and the potential for depression relapse.

Conclusion

Many common antidepressants, particularly SSRIs, can increase bleeding risk due to their impact on platelet serotonin levels. This risk is notably higher when these medications are taken concurrently with NSAIDs, anticoagulants, or in individuals with existing risk factors. Understanding and managing this potential side effect through careful antidepressant selection and protective measures like PPIs are crucial for patient safety. Patients should always discuss their complete medical history and all medications with their healthcare provider to effectively address this risk.

For more in-depth clinical information, consider resources from the National Alliance on Mental Illness (NAMI).

Frequently Asked Questions

Selective Serotonin Reuptake Inhibitors (SSRIs) with high serotonin reuptake inhibition are most frequently associated with bleeding. These include fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft).

Combining SSRIs with NSAIDs like ibuprofen or naproxen significantly increases the risk of gastrointestinal bleeding and should generally be avoided or done only under strict medical supervision. The risk can be many times higher than taking either drug alone.

They interfere with the function of platelets, which are blood cells essential for clotting. Platelets need to absorb serotonin from the blood to work properly. SSRIs block this absorption, leading to impaired platelet aggregation and an increased risk of bleeding.

Antidepressants with little to no effect on serotonin reuptake, such as bupropion (Wellbutrin) and mirtazapine (Remeron), are considered to have a much lower risk of causing bleeding.

Signs can range from mild issues like easy bruising, more frequent nosebleeds (epistaxis), and bleeding gums, to more severe problems like gastrointestinal hemorrhage (blood in stool or vomit) or intracranial bleeding.

The bleeding risk is generally considered more significant and better-documented with SSRIs. While SNRIs also carry a risk due to their effect on serotonin, some studies suggest it may be lower than that of SSRIs, although evidence is conflicting.

The decision to stop an antidepressant like an SSRI before surgery is complex. While they are linked to an increased risk of surgical bleeding, stopping them can cause withdrawal or a relapse of depression. This decision should be made in careful consultation with your surgeon and prescribing physician.