What is the risk of bleeding associated with Selective Serotonin Reuptake Inhibitors (SSRIs) due to their blood thinning effects?

From the Guidelines

SSRIs can increase the risk of bleeding, particularly when combined with other medications that affect bleeding, and patients should be closely monitored for signs of bleeding. The use of SSRIs (selective serotonin reuptake inhibitors) has been associated with an increased risk of bleeding due to their effect on platelet function 1. This risk is particularly concerning when SSRIs are combined with other medications that affect bleeding, such as NSAIDs (ibuprofen, naproxen), aspirin, warfarin, or direct oral anticoagulants. Some key points to consider:

• The bleeding risk is generally modest for most patients taking SSRIs alone but increases significantly with these combinations.
• Patients on SSRIs should inform surgeons before procedures and watch for signs of bleeding like unusual bruising, nosebleeds, blood in urine or stool, or prolonged bleeding from cuts.
• Those with a history of bleeding disorders or taking blood thinners should discuss this risk with their doctor.
• The bleeding risk typically begins within days of starting an SSRI and resolves within 1-2 weeks after discontinuation.
• In most cases, the mental health benefits of SSRIs outweigh this bleeding risk, and patients should not stop these medications without consulting their healthcare provider 1. It is essential to weigh the benefits and risks of SSRI use in individual patients, particularly in those with a history of bleeding disorders or taking medications that affect bleeding. In clinical practice, the following strategies can be employed to minimize the risk of bleeding in patients taking SSRIs:
• Close monitoring for signs of bleeding
• Avoiding the use of SSRIs in combination with other medications that affect bleeding, when possible
• Using the lowest effective dose of SSRIs
• Considering alternative treatments for depression, such as psychotherapy, in patients at high risk of bleeding.

From the FDA Drug Label

SSRIs and SNRIs, including fluoxetine, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anti-coagulants may add to this risk Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages Patients should be cautioned about the risk of bleeding associated with the concomitant use of fluoxetine and NSAIDs, aspirin, or other drugs that affect coagulation SSRIs and SNRIs, including sertraline, may increase the risk of bleeding events ranging from ecchymoses, hematomas, epistaxis, petechiae, and gastrointestinal hemorrhage to life-threatening hemorrhage. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants or other drugs known to affect platelet function may add to this risk

SSRI and Bleeding Risk:

• Increased Risk: SSRIs, including fluoxetine and sertraline, may increase the risk of bleeding events.
• Bleeding Events: Bleeding events related to SSRI use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.
• Concomitant Use: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anti-coagulants may add to the risk of bleeding.
• Patient Caution: Patients should be cautioned about the risk of bleeding associated with the concomitant use of SSRIs and NSAIDs, aspirin, or other drugs that affect coagulation 2 3.

From the Research

SSRI and Bleeding Risk

• The use of selective serotonin reuptake inhibitors (SSRIs) has been associated with an increased risk of bleeding, particularly in the upper gastrointestinal tract 4, 5, 6, 7.
• The risk of bleeding is thought to be due to the inhibition of serotonin reuptake in platelets, leading to impaired platelet function and increased gastric acid secretion 4, 7.
• The concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, and antiplatelet agents with SSRIs can increase the risk of bleeding 4, 5, 6.
• Patients with cirrhosis of the liver or liver failure may also be at increased risk of bleeding when taking SSRIs 4.
• The absolute risk of gastrointestinal bleeding with SSRIs is low, but precautions may be necessary in high-risk patients, such as those with acid-peptic disease or a history of bleeding 4.

Management of Bleeding Risk

• Clinicians should be aware of the risk of bleeding with SSRI use, particularly in patients taking NSAIDs or other medications that increase the risk of bleeding 6.
• Patient education is important for those prescribed NSAIDs and SSRIs concurrently 6.
• Alternative antidepressants with low or no affinity for the serotonin transporter, such as bupropion or mirtazapine, may be considered for patients at high risk of bleeding 6.
• Acid-reducing medications may mitigate the risk of gastrointestinal bleeding in patients taking SSRIs and NSAIDs 6.

Clinical Considerations

• SSRIs are often the first-line treatment for depression, but the risk of bleeding should be considered, particularly in patients with increased cardiovascular risk 8.
• The risk of bleeding versus thrombotic events should be weighed when prescribing SSRIs to patients with a history of stroke or myocardial infarction 8.
• Relevant comorbidity and co-medication should always be taken into account when initiating SSRI treatment 8.