Diclofenac and Amitriptyline: 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
Amitriptyline
Diclofenac
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 amitriptyline (an antidepressant) along with diclofenac (an anti-inflammatory pain reliever, an NSAID). Taking these two together can raise your risk of bleeding. This can range from easy bruising or stomach bleeding to, more rarely, serious bleeding.
The good news is that this is very manageable. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Just watch for warning signs like unusual bruising, black or bloody stools, vomit that looks like coffee grounds, or a sudden bad headache. If any of those happen, get help right away. Your pharmacist or doctor can keep an eye on you and adjust things if needed.
Effect: Increased bleeding risk (including reports of intracranial hemorrhage within 30 days of concomitant use) with an NSAID (diclofenac) plus a TCA (amitriptyline).
Mechanism: Unknown/unspecified. Both agents can independently affect hemostasis; diclofenac inhibits platelet function and irritates GI mucosa, while TCAs may impair platelet serotonin uptake. Neither is a prodrug relevant to this interaction.
Evidence: Established. Severity: Major. Onset: Unspecified.
- Monitor for signs of bleeding (GI, cutaneous, neurologic).
- Consider GI protection and lowest effective NSAID dose/duration.
- Reassess in patients with additional bleeding risk factors or other anticoagulant/antiplatelet therapy.
What happens
An increased risk of bleeding
Interaction Deep Dive
Caution is advised when NSAIDs are given together with tricyclic antidepressants, since this combination can raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of joint use1. If these two drug classes are administered at the same time, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
This combination is used, but your care team will watch you more closely because of the higher bleeding risk.
- Keep taking both as prescribed unless your prescriber tells you to change something.
- Your team may use the lowest effective dose of diclofenac for the shortest time needed, and may add stomach protection.
- Watch for warning signs: unusual bruising, black or bloody stools, blood in vomit, or a sudden severe headache.
Report any of these to your pharmacist or doctor promptly. Also let them know if you take other blood thinners, aspirin, or drink alcohol, since these add to the risk.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The combined use of NSAIDs with antidepressants, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, was associated with a greater risk of intracranial hemorrhage within 30 days of the concurrent use when compared with antidepressant use by itself. No significant difference was found among the antidepressant drug classes with respect to this elevated risk; nevertheless, an increased risk was observed in male patients relative to female patients 1.
Common questions
Can I take Diclofenac and Amitriptyline together?
Combining amitriptyline and diclofenac can increase your risk of bleeding, so keep taking both as prescribed but watch for signs of bleeding and check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diclofenac and Amitriptyline 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 Diclofenac and Amitriptyline interaction managed?
This combination is used, but your care team will watch you more closely because of the higher bleeding risk. Keep taking both as prescribed unless your prescriber tells you to change something. Your team may use the lowest effective dose of diclofenac for the shortest time needed, and may add stomach protection. Watch for warning signs: unusual bruising, black or bloody stools, blood in vomit, or… 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 Diclofenac or Amitriptyline 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 (1)
- 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
Keep reading about Amitriptyline
Keep reading about Diclofenac
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