Sertraline and Indomethacin: 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 recordIndomethacin
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.
You've been prescribed sertraline (an antidepressant) and indomethacin (a strong anti-inflammatory pain reliever, or NSAID). Taken together, they can raise your risk of bleeding. Here's why: sertraline lowers the serotonin your platelets use to help form clots, and indomethacin can irritate the stomach lining and also affects platelets. Combined, they make bleeding more likely, especially in the stomach or gut.
Watch for warning signs like black or bloody stools, vomit that looks like coffee grounds, easy bruising, or nosebleeds that won't stop. The good news is your care team knows how to manage this. Don't stop either medicine on your own, just talk with your pharmacist or doctor.
Effect: Additive bleeding risk (GI and, less commonly, intracranial hemorrhage) with concurrent SSRI plus NSAID.
Mechanism: Sertraline depletes platelet serotonin, impairing platelet aggregation; indomethacin adds antiplatelet effect and direct GI mucosal injury. Additive impairment of hemostasis (a PD interaction, not CYP-mediated). Neither agent's activity depends on the other here.
- Direction: Increased bleeding risk
- Onset: Unspecified
- Evidence: Established; severity major
- Management: Monitor for GI bleeds (higher risk in elderly, prior ulcers). Consider acetaminophen, an antidepressant with less serotonin reuptake inhibition, or gastroprotective prophylaxis (eg, PPI). Individualize per care team.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are taken together with antidepressants, SSRIs included, because of a heightened likelihood of intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding manifestations range from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening 5. In cases where an SSRI is administered alongside an NSAID, keep the patient under close observation for indications of adverse effects such as GI bleeds, particularly among the elderly and individuals with prior GI ulcers. Options to weigh include alternative approaches to pain control (for example, acetaminophen), reassessment of the antidepressant selected (that is, considering drugs with reduced serotonin reuptake inhibition), or the addition of prophylactic antiulcer medication 4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
This combination is used in practice, but it needs care. Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
Your care team may manage this by:
- Watching more closely for bleeding, especially if you are older or have had stomach ulcers
- Considering a different pain option such as acetaminophen
- Reviewing whether a different antidepressant with less effect on serotonin might suit you
- Adding a stomach-protecting medicine (like an acid reducer)
Tell your pharmacist or doctor promptly about black or bloody stools, coffee-ground vomit, unusual bruising, or nosebleeds that won't stop.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Taking NSAIDs together with antidepressants, such as tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, produced a 60% higher risk of intracranial hemorrhage within 30 days of combined use when compared with antidepressant use by itself. No significant difference was observed among the antidepressant drug classes with respect to the elevated risk; nevertheless, male patients carried a greater risk than female patients 1.
b) SSRIs raise the likelihood of upper gastrointestinal (GI) bleeding, and this effect is enhanced when NSAIDs or low-dose aspirin are used at the same time. Hospitalizations for upper GI bleeding were examined in 26,005 users of antidepressant medications and compared with the number of hospitalizations among patients who were not prescribed antidepressants. The number of upper GI bleeding episodes was 3.6 times higher than expected. Using an SSRI together 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 while SSRIs are being used. Combining SSRIs with NSAIDs or low-dose aspirin raised the risk even more 5.
c) Two metaanalyses of upper GI bleed events attributable to SSRIs, NSAIDs, and their combination determined that SSRIs raised the risk by 1.73 6 to 2.36 times 7, NSAIDs by 2.55 times 6, and the SSRI plus NSAID combination by 4.02 6 to 6.33 times 7.
d) The release of serotonin from platelets plays a key role in maintaining hemostasis. Case-control and cohort studies have demonstrated that using SSRIs and NSAIDs together has been linked to a greater risk of bleeding 8.
Common questions
Can I take Sertraline and Indomethacin together?
Combining sertraline and indomethacin raises your bleeding risk, especially in the stomach and gut. Keep taking both as prescribed and ask your pharmacist or doctor about safer pain options or a stomach-protecting medicine, and report any signs of bleeding right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Indomethacin 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 Indomethacin interaction managed?
This combination is used in practice, but it needs care. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your care team may manage this by: Watching more closely for bleeding, especially if you are older or have had stomach ulcers Considering a different pain option such as acetaminophen Reviewing whether a different antidepressant with less effect on serotonin m… 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 Indomethacin 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 Indomethacin
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