From the Guidelines
SSRIs are associated with a small but increased risk of bleeding, particularly when used concurrently with antiplatelet or nonsteroidal anti-inflammatory drugs.
Bleeding Risk on SSRIs
- The odds ratio (OR) for gastrointestinal bleeding with SSRIs is between 1.2 and 1.5, indicating a higher risk compared to other antidepressant medications 1.
- This risk is further increased when SSRIs are used in combination with antiplatelet or nonsteroidal anti-inflammatory drugs, highlighting the need for caution when prescribing SSRIs to patients with a history of bleeding or those taking medications that may increase the risk of bleeding 1.
- A more recent guideline from the American Heart Association/American Stroke Association also notes that SSRIs are associated with a small but increased risk of intracerebral hemorrhage (ICH), particularly in patients taking anticoagulation and strong SSRIs 1.
- However, it's essential to balance the risk of bleeding with the importance of treating depression, and SSRIs may be reserved for patients with moderate to severe depression 1.
- The use of fluoxetine has been evaluated in several randomized trials for stroke motor recovery, and these trials did not show an increased risk of hemorrhagic stroke compared to placebo 1.
From the Research
Bleeding Risk on SSRIs
The use of Selective Serotonin Reuptake Inhibitors (SSRIs) has been associated with an increased risk of bleeding complications.
- A meta-analysis of 32 non-randomized studies found that SSRI users experienced a statistically higher risk of major bleeding compared to non-SSRI users, with a pooled odds ratio of 1.39 (95% CI, 1.23-1.58; p < .001) 2.
- Another study found that SSRI use is associated with roughly doubled odds of upper gastrointestinal (GI) bleeding, and the risk is increased with the concurrent use of NSAIDs, anticoagulants, and antiplatelet agents 3.
- A meta-analysis of observational studies showed a significant association between SSRI use and the risk of bleeding, with a pooled adjusted odds ratio of 1.41 (95% CI 1.27-1.57) 4.
- The risk of upper gastrointestinal bleeding (UGIB) was found to be 1.55-fold higher in SSRI users compared to non-users, with the association being greatest for patients who received concurrent therapy with nonsteroidal anti-inflammatory or antiplatelet drugs 5.
Factors Influencing Bleeding Risk
Several factors can influence the bleeding risk associated with SSRI use, including:
- Concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, and antiplatelet agents, which can increase the risk of bleeding 3, 5.
- Use of acid-suppressing drugs, which can reduce the risk of UGIB 5.
- Presence of bleeding disorders or preceding gastrointestinal lesions, which can increase the risk of bleeding 6.
- Use of SSRIs with a high potential for drug interaction, which can increase the risk of bleeding 6.
Clinical Implications
The increased risk of bleeding associated with SSRI use has important clinical implications, including:
- The need for caution when co-prescribing SSRIs with antithrombotic therapy (either anticoagulant or antiplatelet) 2.
- The importance of considering the risk-benefit ratio when prescribing SSRIs, particularly in high-risk patients 2, 3.
- The need for close monitoring of high-risk patients and consideration of alternative treatments or gastroprotective agents 6.