What is the association between Bupropion (Wellbutrin) and gastrointestinal (GI) bleeding?

From the Guidelines

Bupropion is not typically associated with an increased risk of gastrointestinal (GI) bleeding, and it can be a safer option for patients with a history of GI bleeding compared to other antidepressants like SSRIs. Unlike medications such as NSAIDs (ibuprofen, naproxen), aspirin, or selective serotonin reuptake inhibitors (SSRIs), bupropion does not significantly affect platelet function or gastric mucosa integrity. Bupropion works primarily by inhibiting the reuptake of dopamine and norepinephrine, rather than serotonin, which is why it doesn't carry the same GI bleeding risk as SSRIs 1. Common side effects of bupropion may include nausea, vomiting, constipation, or dry mouth, but these are generally mild and transient. Some key points to consider when prescribing bupropion to patients with a history of GI bleeding include:

• Starting with a low dose (150 mg daily) and potentially increasing to 300 mg daily
• Monitoring patients for any unusual bleeding or GI symptoms while taking bupropion
• Performing a comprehensive risk assessment for patients with both depression and a high risk of GI bleeding
• Individualizing medication choices based on the patient's specific medical history and risk factors. It's also important to note that the study by de Abajo et al, as mentioned in 1, raises the possibility of an increased risk of upper gastrointestinal bleeding associated with selective serotonin reuptake inhibitors, but this does not apply to bupropion.

From the FDA Drug Label

Altered PT and/or INR, associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin. Digestive ... gastrointestinal hemorrhage, gum hemorrhage, hepatitis, intestinal perforation, liver damage, pancreatitis, and stomach ulcer Hemic and Lymphatic ... Ecchymosis, anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia.

The FDA drug label mentions that gastrointestinal hemorrhage and gum hemorrhage were reported as adverse reactions in patients taking bupropion. Additionally, altered PT and/or INR associated with hemorrhagic complications were observed when bupropion was coadministered with warfarin.

• Bupropion may increase the risk of GI bleeds, particularly when coadministered with other medications that affect coagulation, such as warfarin.
• Key words: Bupropion, GI bleeds, warfarin, hemorrhagic complications 2

From the Research

Bupropion and GI Bleeds

• Bupropion is an antidepressant that may have a lower risk of gastrointestinal (GI) bleeding compared to selective serotonin reuptake inhibitors (SSRIs) 3.
• A systematic review and meta-analysis found that mirtazapine and bupropion, which lack serotonin reuptake inhibition, may not be suitable alternatives for patients at risk of bleeding, as the evidence for their safety is insufficient 4.
• The risk of GI bleeding with bupropion is not well-established, but it is thought to be lower than with SSRIs, which increase the risk of bleeding by 1.16- to 2.36-fold 3.
• Concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) and SSRIs increases the risk of GI bleeding, with an odds ratio (OR) range of 3.17-10.9 3.
• Acid-reducing medications may mitigate the risk of GI bleeds in chronic NSAID and SSRI users, with an OR range of 0.98-1.1 3.

Comparison with SSRIs

• SSRIs are associated with a modest increase in the risk of upper GI bleeding, with an OR of 1.66 (95% CI 1.44-1.92) in case-control studies and 1.68 (95% CI 1.13-2.50) in cohort studies 5.
• The risk of upper GI bleeding is further increased with the use of both SSRIs and NSAIDs, with an OR of 4.25 (95% CI 2.82-6.42) 5.
• A network meta-analysis found that concurrent use of SSRIs and NSAIDs increases the risk of GI bleeding, with an OR of 2.14 (95% CI 1.52-3.02) compared to SSRI users 6.
• The results of these studies suggest that bupropion may be a safer alternative to SSRIs in terms of GI bleeding risk, but more research is needed to confirm this 4.

Clinical Implications

• Clinicians should be aware of the risk of bleeding with SSRI use, especially for patients taking NSAIDs, and consider alternative treatments such as bupropion for patients at high risk of bleeding 3, 7.
• Patient education is important for those prescribed NSAIDs and SSRIs concurrently, as the risk of GI bleeding is increased with concurrent use 3, 7.
• Further research is needed to fully understand the risk of GI bleeding with bupropion and to determine the safest treatment options for patients at risk of bleeding 4.