Sertraline and Salsalate: 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 recordSalsalate
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 and salsalate together can raise your risk of bleeding. Sertraline is an antidepressant (an SSRI). One thing it does is make your platelets, the tiny cells that help your blood clot, a little less sticky. Salsalate is an NSAID pain reliever that can irritate the stomach lining and also affects clotting. Put together, they can make bleeding easier, especially in the stomach or gut.
Watch for signs like black or tarry stools, vomit that looks like coffee grounds, easy bruising, nosebleeds, or blood in your stool. This is very manageable. Keep taking both as prescribed and talk with your pharmacist or doctor, who can adjust your plan and keep a closer eye on you.
Effect: Additive bleeding risk, notably GI and intracranial hemorrhage.
Mechanism: SSRIs (sertraline) deplete platelet serotonin, impairing platelet aggregation; salsalate (NSAID) adds direct GI mucosal injury and antiplatelet effects. Pharmacodynamic, additive. Neither agent's effect depends on prodrug activation here.
Evidence: Established. Severity: Major. Onset unspecified.
Management:
- Monitor for GI bleed, bruising, epistaxis, melena; higher risk in elderly and prior PUD.
- Consider acetaminophen for analgesia where appropriate.
- Consider an antidepressant with less serotonin reuptake inhibition.
- Consider gastroprotection (eg, PPI) if combination continues.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are combined with antidepressants, SSRIs included, because doing so raises the likelihood of intracranial hemorrhage1 as well as gastrointestinal (GI) bleeding6. Reported bleeding episodes have encompassed epistaxis, ecchymosis, hematoma, petechiae, and hemorrhages that are life-threatening5. If an SSRI is administered together with an NSAID, keep close watch on the patient for indications of adverse events such as GI bleeds, particularly among the elderly and individuals with prior GI ulcers. Alternative approaches to pain control may be considered (for example, acetaminophen), the selected antidepressant can be reassessed (that is, consider agents that produce less serotonin reuptake inhibition), or antiulcer medications may be prescribed as prophylaxis4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
This combination is manageable with the right precautions. Keep taking both medicines as prescribed unless your care team tells you otherwise.
Your pharmacist or prescriber may:
- Watch you more closely for bleeding, especially if you are older or have had stomach ulcers.
- Suggest a different pain option such as acetaminophen when appropriate.
- Review your antidepressant choice.
- Add a stomach-protecting medicine to lower GI bleed risk.
Contact them promptly if you notice black or tarry stools, blood in vomit or stool, unusual bruising, or nosebleeds. Seek urgent care for severe or sudden symptoms.
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, led to a 60% higher risk of intracranial hemorrhage within 30 days of combined use when compared to using an antidepressant by itself. No meaningful difference in the elevated risk was observed among the antidepressant drug classes; nonetheless, male patients had 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 against 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. 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. Concurrent use of SSRIs with NSAIDs or low-dose aspirin increased the risk still further 5.
c) Two metaanalyses examining cases of upper GI bleeding 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 combination of SSRIs and NSAIDs by 4.02 6 to 6.33 times 7.
d) The release of serotonin from platelets plays an important role in sustaining 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 Salsalate together?
Using sertraline with salsalate raises the risk of bleeding, especially in the stomach and gut. Keep taking both as prescribed, watch for bleeding signs, and ask your pharmacist or doctor whether a safer pain option or stomach protection makes sense for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Salsalate 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 Salsalate interaction managed?
This combination is manageable with the right precautions. Keep taking both medicines as prescribed unless your care team tells you otherwise. Your pharmacist or prescriber may: Watch you more closely for bleeding, especially if you are older or have had stomach ulcers. Suggest a different pain option such as acetaminophen when appropriate. Review your antidepressant choice. Add a stomach-protecti… 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 Salsalate 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
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