The three categories at a glance
Paracetamol is generally considered safe with antidepressants and is often the first choice for occasional pain relief. No significant interaction is documented in major prescribing resources. Standard adult dosing applies.
NSAIDs (ibuprofen, naproxen, aspirin) can be used with antidepressants but with caution. The concern is a slightly increased bleeding risk when NSAIDs are combined with SSRIs and SNRIs — documented in NPS MedicineWise and TGA product information. Occasional short-term use is usually fine; regular long-term use is worth discussing with your prescriber or pharmacist.
Opioids (codeine, tramadol, oxycodone) have more significant potential interactions with some antidepressants — including serotonin syndrome risk with tramadol specifically. Do not start these without prescriber knowledge. If you are prescribed an opioid short-term (after surgery, for example), tell the prescribing doctor about your antidepressant so they can choose the safest option.
What to flag to your prescriber
Mention these at your next appointment
- Any unusual bleeding while using NSAIDs alongside your antidepressant.
- New nausea, sweating, or confusion after starting a new painkiller — possible serotonin syndrome.
- Regular use of any painkiller beyond a few days.
- Chronic pain requiring ongoing painkiller use — this warrants a dedicated conversation.
If you experience nausea after combining a painkiller with your antidepressant, note the timing — it helps your prescriber work out whether it is from the painkiller, the antidepressant, or an interaction.
Frequently asked questions
Can I take paracetamol with my antidepressant?
Generally yes. Paracetamol has no significant interaction with most antidepressants and is typically the preferred option for occasional pain relief while on an antidepressant.
Is ibuprofen safe with antidepressants?
Occasional use is usually fine. Regular use is worth discussing with your pharmacist due to a slightly increased bleeding risk when combined with SSRIs and SNRIs. Paracetamol is preferred for frequent use.
What about codeine or tramadol?
Do not start these without prescriber knowledge. Tramadol in particular can interact with antidepressants and carries a serotonin syndrome risk. Always inform any prescribing doctor about your antidepressant before starting an opioid.
Evidence and sources referenced
- NICE Guideline NG222 — Depression in adults: treatment and management (United Kingdom).
- Royal Australian and New Zealand College of Psychiatrists (RANZCP) — Clinical Practice Guidelines for Mood Disorders.
- NPS MedicineWise — patient and prescriber resources on antidepressants (Australia).
- Royal College of Psychiatrists — patient information on antidepressants.
- TGA and FDA — product information for SSRI and SNRI classes.
- Maudsley Prescribing Guidelines in Psychiatry.
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