Sertraline and Sulindac: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Sertraline
No brand names on recordSulindac
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.
Taking sertraline with sulindac can raise your risk of bleeding. Sertraline is an antidepressant (an SSRI), and one thing it does is make your platelets a little less able to form clots. Sulindac is an anti-inflammatory pain reliever (an NSAID) that can irritate the stomach lining and also affects how platelets work. Put together, they add up, so bleeding, especially in the stomach or gut, becomes more likely.
Please don't stop either medicine on your own. Watch for warning signs like black or bloody stools, vomit that looks like coffee grounds, easy bruising, or nosebleeds, and tell your doctor or pharmacist right away. Your care team can manage this safely.
Effect: Additive increased bleeding risk (GI and intracranial hemorrhage) with concurrent SSRI and NSAID use.
Mechanism: Sertraline depletes platelet serotonin, impairing serotonin-mediated platelet aggregation; sulindac inhibits platelet cyclooxygenase and is directly GI-mucosa toxic. Effects on hemostasis are additive (a pharmacodynamic interaction, not PK).
Evidence: Established. Severity: Major. Onset unspecified.
- Monitor for epistaxis, ecchymosis, hematoma, petechiae, and GI/intracranial bleeding.
- Higher risk in elderly and patients with prior GI ulcers or bleeds.
- Consider acetaminophen for pain, an antidepressant with less serotonergic reuptake inhibition, or add PPI/gastroprotective prophylaxis.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and antidepressants, SSRIs among them, are used together, because this combination raises the likelihood of intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding manifestations have ranged from epistaxis, ecchymosis, hematoma, and petechiae to life-threatening hemorrhages 5. In cases where an SSRI is administered alongside an NSAID, watch the patient carefully for indications of adverse events such as GI bleeds, particularly among elderly patients and those with a prior history of GI ulcers. Options to consider include alternative approaches to pain control (for example, acetaminophen), reassessing the selected antidepressant (that is, favoring agents with weaker serotonin reuptake inhibition), or providing prophylaxis using antiulcer medications 4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
This combination is used sometimes, but with caution and monitoring. Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
Your care team may:
- Watch you more closely for bleeding, especially if you are older or have had stomach ulcers or GI bleeds.
- Suggest a different pain option such as acetaminophen where appropriate.
- Review your antidepressant choice, or add a stomach-protecting medicine (such as an antiulcer drug).
Tell your pharmacist or doctor right away about black or bloody stools, coffee-ground vomit, unusual bruising, or nosebleeds. Ask before adding other NSAIDs like ibuprofen or naproxen.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Taking NSAIDs together with antidepressants, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, led to a 60% higher risk of intracranial hemorrhage within 30 days of combined use when compared with antidepressant use by itself. No meaningful difference in the elevated risk was found across the antidepressant drug classes; however, male patients carried a greater risk than female patients 1.
b) SSRIs raise the likelihood of upper gastrointestinal (GI) bleeding, and this effect is amplified when NSAIDs or low-dose aspirin are used at the same time. Hospitalizations for upper GI bleeding were examined among 26,005 people using antidepressant medications and compared with the number of hospitalizations in patients who were not prescribed antidepressants. The number of upper GI bleeding events was 3.6 times higher than anticipated. Using an SSRI along with NSAIDs or low-dose aspirin raised the risk to 12.2 and 5.2 times, respectively. The results of this study show a heightened risk of upper GI bleeding during SSRI use. Concurrent use of SSRIs with NSAIDs or low-dose aspirin increased the risk still further 5.
c) Two metaanalyses examining upper GI bleed events attributable to SSRIs, NSAIDs, and their combination found that SSRIs raised 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) Serotonin released by platelets plays an important role in maintaining hemostasis. Case-control and cohort studies have demonstrated that using SSRIs together with NSAIDs has been linked to a higher risk of bleeding 8.
Common questions
Can I take Sertraline and Sulindac together?
Combining sertraline and sulindac adds up to a higher risk of bleeding, especially in the stomach and gut, so watch for bleeding signs and check with your doctor or pharmacist about safer pain options or added stomach protection. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Sulindac 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 is the Sertraline and Sulindac interaction managed?
This combination is used sometimes, but with caution and monitoring. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your care team may: Watch you more closely for bleeding, especially if you are older or have had stomach ulcers or GI bleeds. Suggest a different pain option such as acetaminophen where appropriate. Review your antidepressant choice, or add a stoma… Management is individual — always follow your own care team's guidance.
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 Sertraline or Sulindac 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. PubMed
- Product Information: CELEXA(R) oral tablets, citalopram oral tablets. Allergan USA Inc (per FDA), Madison, NJ, 2023. DailyMed
Keep reading about Sertraline
Keep reading about Sulindac
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