What is the interaction between Trazodone (an antidepressant) and Ibuprofen (a nonsteroidal anti-inflammatory drug, NSAID)?

From the Guidelines

Trazodone and ibuprofen can generally be taken together, but it is crucial to consider the potential for increased gastrointestinal risk, particularly in patients with a history of gastrointestinal complications or those taking other medications that may interact with ibuprofen, such as aspirin 1. When taking trazodone and ibuprofen together, it is essential to maintain at least a 2-hour separation between taking them to minimize any potential for minor interactions. Trazodone is an antidepressant often prescribed for insomnia at doses of 50-100mg before bedtime, while ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) typically taken at 200-400mg every 4-6 hours for pain or inflammation.

• Both medications can cause stomach irritation, so taking them with food can help reduce this side effect.
• If you experience unusual drowsiness, dizziness, or stomach pain when using these medications together, contact your healthcare provider.
• This combination is generally safe because they work through different mechanisms in the body - trazodone primarily affects serotonin receptors in the brain while ibuprofen inhibits prostaglandin production in the body's tissues.
• Always inform your doctor about all medications you're taking to ensure there are no concerns specific to your health situation, especially if you are taking aspirin or other NSAIDs, as the combination of these medications can increase the risk of gastrointestinal complications 1. It is also important to note that the use of proton pump inhibitors (PPIs) may be beneficial in reducing the risk of gastrointestinal complications in patients taking ibuprofen, especially those with a history of gastrointestinal complications or those taking other medications that may interact with ibuprofen 1.

From the FDA Drug Label

Increased Risk of Bleeding Inform patients about the concomitant use of Trazodone Hydrochloride Tablets with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use of drugs that interfere with serotonin reuptake and these medications has been associated with an increased risk of bleeding Key Points:

• The use of trazodone with NSAIDs, such as ibuprofen, may increase the risk of bleeding.
• Patients should inform their healthcare providers if they are taking or planning to take any medications that increase the risk of bleeding. The FDA drug label warns about the increased risk of bleeding when trazodone is used with NSAIDs like ibuprofen 2.

From the Research

Trazodone and Ibuprofen Interaction

• There is no direct evidence of an interaction between trazodone and ibuprofen in the provided studies.
• However, studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen can increase the risk of gastrointestinal bleeding 3, 4, 5, 6, 7.
• Trazodone is an antidepressant that can increase the risk of bleeding when combined with other medications, such as NSAIDs 4.
• The risk of gastrointestinal bleeding is higher when NSAIDs are combined with selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants that includes trazodone 4.
• Prescribers should exercise caution when administering NSAIDs and SSRIs concurrently, especially in patients with higher risks of GI bleeding 4.

Gastrointestinal Bleeding Risk

• The risk of gastrointestinal bleeding is higher in patients who use both NSAIDs and proton pump inhibitors (PPIs) compared to those who use NSAIDs only 5.
• The risk of upper GI bleeding is significantly higher in elderly acute users of NSAIDs or regular-dose aspirin compared to chronic users 6.
• Co-treatment with proton pump inhibitors may reduce the risk of bleeding in acute NSAID or aspirin users 6.
• Selective cyclo-oxygenase (COX)-2 inhibitors are as effective as adding PPIs in preventing upper and lower gastrointestinal complications 7.

Prevention and Treatment

• Limiting NSAID use or co-administration with proton pump inhibitors (PPIs) can reduce dyspepsia, peptic ulcer disease, and rates of complications 7.
• Helicobacter pylori eradication and co-medication with a proton pump inhibitor (PPI) are primary and secondary prevention options for gastrointestinal bleeding 3.