Sertraline and Proquazone: 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 recordProquazone
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.
Taking sertraline with proquazone can raise your risk of bleeding. Sertraline is an antidepressant (an SSRI), and proquazone is an anti-inflammatory pain medicine (an NSAID). On their own, SSRIs make platelets a little less able to form clots, and NSAIDs can irritate the stomach lining. Put together, they can add up and make bleeding more likely, such as nosebleeds, easy bruising, or more serious bleeding in the stomach or gut.
This is more of a concern if you are older or have had stomach ulcers. Please don't stop either medicine on your own. Talk with your pharmacist or doctor. They have good ways to manage this safely.
Effect: Additive bleeding risk (GI hemorrhage, intracranial hemorrhage, epistaxis, ecchymosis, petechiae).
Mechanism: Sertraline (SSRI) depletes platelet serotonin, impairing platelet aggregation; proquazone (NSAID) adds antiplatelet and GI mucosal effects. Additive PD interaction, not a prodrug/CYP-mediated issue.
- Direction: Increased bleeding risk
- Severity/Evidence: Major; established
- Onset: Unspecified
Management: Monitor for GI bleeding and other bleeding signs, especially in elderly patients or those with prior ulcers. Consider acetaminophen for analgesia, an antidepressant with less serotonin reuptake inhibition, or gastroprotective prophylaxis (PPI/H2RA). Individualize therapy.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and antidepressants, SSRIs among them, are taken together, since this combination raises the likelihood of intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding episodes have ranged from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening 5. In cases where an SSRI is administered alongside an NSAID, the patient should be watched carefully for indications of adverse events such as GI bleeds, particularly among the elderly and individuals with a prior history of GI ulcers. Options to consider include alternative approaches to pain control (for example, acetaminophen), reassessment of the selected antidepressant (that is, choosing agents with reduced serotonin reuptake inhibition), or the addition of antiulcer medications as prophylaxis 4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is manageable when everyone is aware of it.
- Your care team may monitor you more closely for signs of bleeding, especially if you are older or have had a stomach ulcer.
- They may consider a different pain option (such as acetaminophen), review your antidepressant choice, or add a stomach-protecting medicine.
- Tell your pharmacist or doctor right away if you notice black or bloody stools, vomiting blood, unusual bruising, nosebleeds, or a severe headache.
Bring this up at your next visit so your plan can be tailored to you.
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 to antidepressant use by itself. No meaningful difference was found between the various antidepressant drug classes with respect to this elevated risk; nevertheless, the risk was higher in male patients than in 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. Hospital admissions for upper GI bleeding were examined among 26,005 users of antidepressant drugs and compared with the number of admissions in patients who had no prescriptions for antidepressants. The number of upper GI bleeding events was 3.6 times higher 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 greater 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 examining cases of upper GI bleeding related 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 serotonin released by platelets plays an important role in maintaining hemostasis. Case-control and cohort studies have demonstrated that using SSRIs and NSAIDs together has been linked to a heightened risk of bleeding 8.
Common questions
Can I take Sertraline and Proquazone together?
Combining sertraline with the NSAID proquazone increases bleeding risk, especially stomach and gut bleeding. Don't stop either drug on your own; ask your pharmacist or doctor, who can monitor you or adjust your pain or antidepressant plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Proquazone 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 Proquazone interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is manageable when everyone is aware of it. Your care team may monitor you more closely for signs of bleeding, especially if you are older or have had a stomach ulcer. They may consider a different pain option (such as acetaminophen), review your antidepressant choice, or add a stomach-protecting 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 Proquazone 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 Proquazone
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