Sertraline and Tolmetin: 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 recordTolmetin
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're taking sertraline (an antidepressant) and tolmetin (an anti-inflammatory pain reliever, like ibuprofen). Used together, they can raise your chance of bleeding. Sertraline lowers the amount of serotonin your platelets use to help form clots, and tolmetin can irritate the stomach lining. Put together, that means a higher risk of stomach bleeds and, less commonly, other bleeding.
Watch for warning signs like black or bloody stools, vomit that looks like coffee grounds, easy bruising, nosebleeds, or stomach pain. This risk is real but very manageable. Please don't stop either medicine on your own. Talk with your pharmacist or doctor so they can guide you.
Effect: Additive bleeding risk (GI and, rarely, intracranial hemorrhage) with concurrent SSRI + NSAID.
Mechanism: Sertraline depletes platelet serotonin, impairing platelet aggregation; tolmetin inhibits platelet COX and is directly gastroerosive. Additive effect on hemostasis. Neither is a prodrug here; this is a pharmacodynamic interaction.
Evidence: Established. Severity: Major. Onset unspecified.
Management:
- Monitor for GI bleed, bruising, epistaxis, especially elderly or prior PUD.
- Consider acetaminophen instead of an NSAID.
- Consider gastroprotection (eg, PPI) if NSAID continued.
- Consider an antidepressant with less serotonergic reuptake inhibition.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are combined with antidepressants, SSRIs among them, given the heightened potential for intracranial hemorrhage1 as well as gastrointestinal (GI) bleeding6. Reported bleeding manifestations have ranged from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening5. If an SSRI is administered together with an NSAID, watch the patient carefully for indications of adverse effects such as GI bleeds, particularly among the elderly and individuals with a prior history of GI ulcers. Options to weigh include alternative approaches to pain control (eg, acetaminophen), reassessment of the selected antidepressant (that is, choosing agents that produce less serotonin reuptake inhibition), or the use of antiulcer medications for prophylaxis4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
The good news is your care team can manage this well. Keep taking both medicines as prescribed unless your prescriber tells you otherwise.
Your team may choose to:
- Watch you more closely for bleeding, especially if you are older or have had stomach ulcers.
- Consider a different pain reliever such as acetaminophen (Tylenol) instead of the NSAID.
- Add a stomach-protecting medicine if you stay on the NSAID.
- Review whether a different antidepressant might be a better fit.
Call your pharmacist or doctor promptly if you notice black or bloody stools, coffee-ground vomit, unusual bruising, or nosebleeds.
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, compared with taking an antidepressant by itself. No meaningful difference in this elevated risk was found across the antidepressant drug classes; however, the risk was greater in male patients than in female patients 1.
b) SSRIs raise the likelihood of upper gastrointestinal (GI) bleeding, and this effect is amplified by simultaneous use of NSAIDs or low-dose aspirin. Hospitalizations for upper GI bleeding were identified among 26,005 users of antidepressant medications and compared with the number of hospitalizations in patients who were not prescribed antidepressants. The number of upper GI bleeding episodes was 3.6 times greater than anticipated. Concurrent use of an SSRI with NSAIDs or with 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. Combined use of SSRIs with NSAIDs or low-dose aspirin raised the risk still further 5.
c) Two meta-analyses examining occurrences of upper GI bleed 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 and NSAID combination by 4.02 6 to 6.33 times 7.
d) The secretion of serotonin from platelets plays a role in preserving 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 Tolmetin together?
Combining sertraline and tolmetin raises bleeding risk, mainly in the stomach. Keep taking both as prescribed, watch for signs of bleeding, and ask your pharmacist or doctor about safer pain options or stomach protection. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Tolmetin 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 Tolmetin interaction managed?
The good news is your care team can manage this well. Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Your team may choose to: Watch you more closely for bleeding, especially if you are older or have had stomach ulcers. Consider a different pain reliever such as acetaminophen (Tylenol) instead of the NSAID. Add a stomach-protecting medicine if you stay on the N… 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 Tolmetin 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 Tolmetin
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