Sertraline and Pranoprofen: 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 recordPranoprofen
No brand names on record
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 pranoprofen (an anti-inflammatory pain reliever, or NSAID). Taken together, these two can raise your risk of bleeding. Here's why: sertraline lowers the amount of serotonin your platelets use to help form clots, and NSAIDs like pranoprofen can irritate the stomach lining. Put together, that means a higher chance of things like nosebleeds, easy bruising, or bleeding in the stomach.
This doesn't mean you can't take both. It just means your care team will watch you a bit more closely. Please don't stop either medicine on your own, but do tell your pharmacist or doctor about any unusual bruising, black or bloody stools, or stomach pain.
Effect: Additive bleeding risk (GI and, less commonly, intracranial hemorrhage) with concurrent SSRI and NSAID.
Mechanism: Sertraline depletes platelet serotonin, impairing platelet aggregation; pranoprofen adds antiplatelet and gastric mucosal effects. Neither is a prodrug in a way that alters this direction. Effect is additive on hemostasis.
- Severity/evidence: Major; established.
- Onset: Unspecified.
- At-risk: Elderly, prior GI ulcer/bleed, anticoagulant/antiplatelet use.
- Management: Monitor for epistaxis, ecchymosis, melena, and GI bleed signs. Consider acetaminophen instead, an antidepressant with less serotonin reuptake inhibition, or gastroprotective prophylaxis (eg, PPI).
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and antidepressants, SSRIs among them, are taken together, given the heightened likelihood of intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding manifestations have ranged from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening 5. In cases where an SSRI is combined with an NSAID, keep a close watch on the patient for indications of adverse events such as GI bleeds, with particular attention to elderly individuals and those who have previously had GI ulcers. Alternatives worth weighing include other approaches to pain control (for instance, acetaminophen), reassessing the antidepressant selected (that is, favoring agents that inhibit serotonin reuptake to a lesser degree), 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 manageable, and many people take an SSRI and an NSAID together with monitoring. Keep taking both as prescribed unless your doctor tells you otherwise.
- Watch for bleeding signs: nosebleeds, easy bruising, black or bloody stools, vomiting that looks like coffee grounds, or unusual stomach pain.
- Ask your care team whether acetaminophen could work for your pain instead of the NSAID.
- They may also consider a stomach-protecting medicine or reviewing your antidepressant choice.
- Extra caution applies if you are older or have a history of ulcers or GI bleeds.
Bring up any of these signs promptly with your pharmacist or prescriber.
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, produced a 60% higher risk of intracranial hemorrhage within 30 days of combined use compared with using an antidepressant by itself. No meaningful difference in this elevated risk was observed among the antidepressant drug classes; however, male patients carried a higher risk than female patients 1.
b) SSRIs raise the likelihood of upper gastrointestinal (GI) bleeding, and this effect is intensified when NSAIDs or low-dose aspirin are used at the same time. Hospitalizations for upper GI bleeding were reviewed 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. 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 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 secretion of serotonin from 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 greater risk of bleeding 8.
Common questions
Can I take Sertraline and Pranoprofen together?
Combining sertraline with the NSAID pranoprofen raises the risk of bleeding, especially in the stomach. Keep taking both as prescribed but watch for bleeding signs and ask your care team about safer pain options like acetaminophen or adding stomach protection. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Pranoprofen 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 Pranoprofen interaction managed?
This combination is manageable, and many people take an SSRI and an NSAID together with monitoring. Keep taking both as prescribed unless your doctor tells you otherwise. Watch for bleeding signs: nosebleeds, easy bruising, black or bloody stools, vomiting that looks like coffee grounds, or unusual stomach pain. Ask your care team whether acetaminophen could work for your pain instead of the NSAID… 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 Pranoprofen 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 Pranoprofen
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