Aspirin and Paroxetine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Paroxetine
Aspirin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of bleeding
Interaction Deep Dive
Use caution with the concomitant use of NSAIDs and antidepressants, including SSRIs due to an increased risk of intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Bleeding events have included epistaxis, ecchymosis, hematoma, petechiae, and life-threatening hemorrhages 5. When an SSRI and an NSAID are given concurrently, closely monitor the patient for signs of adverse events, including GI bleeds, especially in elderly and those with a history of GI ulcers. Consider other types of pain management (eg, acetaminophen), review the chosen antidepressant (ie, consider agents with less serotonin reuptake inhibition), or prescribe prophylaxis with antiulcer drugs 4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
Literature reports
4 reports — tap to read
a) Concomitant use of NSAIDs and antidepressants, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, resulted in a 60% increased risk of intracranial hemorrhage within 30 days of concomitant use compared with antidepressant use alone. There was no significant difference between the antidepressant drug classes and the increased risk; however, there was an increased risk associated with male patients compared with female patients 1.
b) SSRIs increase the risk of upper gastrointestinal (GI) bleeding, and this effect is potentiated by concurrent use of NSAIDs or low-dose aspirin. Hospitalizations for upper GI bleeding were searched among 26,005 users of antidepressant medications and compared with the number of hospitalizations in those patients who did not receive prescriptions for antidepressants. The amount of upper GI bleeding episodes was 3.6 times more than expected. Combined use of an SSRI and NSAIDs or low-dose aspirin increased the risk to 12.2 and 5.2 times, respectively. The findings of this study demonstrate an increased risk of upper GI bleeding during the use of SSRIs. Combined use of SSRIs and NSAIDs or low-dose aspirin increased the risk even further 5.
c) Two metaanalyses of incidents of upper GI bleed due to SSRIs, NSAIDs, and their combination found that SSRIs increased the risk by 1.73 6 to 2.36 times 7, NSAIDs by 2.55 times 6, and the combination of SSRIs and NSAIDs by 4.02 6 to 6.33 times 7.
d) The release of serotonin by platelets is important for maintaining hemostasis. Case-control and cohort studies have shown that the combined use of SSRIs and NSAIDs have been associated with an increased risk of bleeding 8.
Common questions
Can I take Aspirin and Paroxetine together?
An increased risk of bleeding Always confirm with your pharmacist or prescriber before making any change.
How serious is the Aspirin and Paroxetine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Aspirin or Paroxetine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (8)
- Shin JY, Park MJ, Lee SH, et al: Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study. BMJ 2015; 351:h3517. PubMed
- Product Information: VIMOVO(TM) delayed release oral tablets, naproxen and esomeprazole magnesium delayed release oral tablets. AstraZeneca LPW, Wilmington, DE, 2010. DailyMed
- Product Information: SPRIX(TM) nasal spray, ketorolac tromethamine nasal spray. Roxro Pharma, Inc, Menlo Park, CA, 2009. DailyMed
- Mort JR, Aparasu RR, & Baer RK: Interaction between selective serotonin reuptake inhibitors and nonsteroidal antiinflammatory drugs: review of the literature. Pharmacotherapy 2006; 26(9):1307-1313. PubMed
- Dalton S, Johansen C, Mellemkjoer L, et al: Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding. Arch Intern Med 2003; 163:59-64. DOI
- Oka Y, Okamoto K, Kawashita N, et al: Meta-analysis of the risk of upper gastrointestinal hemorrhage with combination therapy of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Biol Pharm Bull 2014; 37(6):947-953. PubMed
- Loke YK, Trivedi AN, & Singh S: Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2008; 27(1):31-40. DOI
- Product Information: CELEXA(R) oral tablets, citalopram oral tablets. Allergan USA Inc (per FDA), Madison, NJ, 2023. DailyMed
Keep reading about Paroxetine
Keep reading about Aspirin
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