Based on PubMed | Is it safe to take fluoxetine with fish oil (omega-3) supplements, or do they interact?

Most people can take fluoxetine (an SSRI antidepressant) and fish oil (omega‑3) together, and they generally do not have a direct, dangerous interaction. The main practical consideration is a small, additive increase in bleeding tendency because fluoxetine can impair platelet serotonin and omega‑3s have mild antiplatelet effects, so it’s reasonable to watch for easy bruising or nosebleeds especially if you also use aspirin, NSAIDs like ibuprofen/naproxen, or blood thinners. ^{[1] [2]}

What we know about fluoxetine and bleeding risk

• SSRIs, including fluoxetine, can increase the risk of bleeding by reducing serotonin in platelets, which impairs normal clotting. This risk is higher when SSRIs are combined with other agents that affect clotting, particularly NSAIDs (aspirin, ibuprofen, naproxen) or anticoagulants (warfarin and similar). ^{[1] [2]}
• Drug labels and clinical guidance note reports ranging from minor bruising and nosebleeds to gastrointestinal bleeding, with the risk potentiated by NSAIDs or aspirin. People on blood thinners should be especially cautious and discuss any new supplement with their clinician. ^{[3] [4]}

What we know about omega‑3 (fish oil) with antidepressants

• Omega‑3 supplements (EPA and DHA) have been studied as add‑on therapy in depression; trials suggest they may offer modest symptom benefits for some people, particularly those without significant anxiety, and they are generally well tolerated. These studies did not identify a signal for serotonin syndrome when omega‑3s were combined with SSRIs like fluoxetine. ^[5]
• In small clinical work comparing fluoxetine, EPA, and their combination, the combo improved depressive symptoms and did not show abnormal safety signals related to serotonin or severe adverse events. Biomarker studies from that trial found decreases in cortisol across groups, again without unique combination toxicity. ^[6]

Serotonin syndrome risk

• Serotonin syndrome is a rare but serious condition that usually occurs when two or more serotonergic drugs are combined (for example, SSRIs with MAO inhibitors or certain other serotonergic agents). Fish oil is not serotonergic and is not known to precipitate serotonin syndrome with fluoxetine. ^[2]

Practical safety tips

• If you take fluoxetine alone and want to add a standard omega‑3 dose (often 1–2 grams/day combined EPA+DHA), this is generally considered reasonable for most adults. Monitor for signs of bleeding such as unusual bruising, prolonged nosebleeds, bleeding gums, black stools, or vomiting blood, and seek medical advice if these occur. ^{[1] [3]}
• Use extra caution if you also take aspirin, ibuprofen, naproxen, celecoxib, warfarin, or other anticoagulants/antiplatelets, as these combinations can cumulatively raise bleeding risk. Discuss with your clinician before starting fish oil if you’re on these medicines or have a bleeding disorder, upcoming surgery, or a history of stomach ulcers. ^{[1] [2]}
• Keep your fluoxetine prescriber informed about all supplements, including omega‑3, since they will consider your full medication list and personal risk factors. They may suggest protective measures (for example, avoiding unnecessary NSAIDs) if you proceed. ^{[1] [2]}

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Quick reference table

Topic	Fluoxetine alone	Fish oil alone	Together
Serotonin syndrome	Possible with other serotonergic drugs; not expected with fish oil	Not serotonergic	No known added risk beyond fluoxetine’s baseline
Bleeding tendency	Slightly increased; higher with NSAIDs/anticoagulants	Mild antiplatelet effect at common doses	Small additive effect; caution with NSAIDs/anticoagulants and watch for bruising/bleeding [1] [2] [3]
Depression outcomes	Evidence‑based antidepressant	May modestly help in some, especially without comorbid anxiety	Can be complementary in some studies; generally well tolerated [5] [6]

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Bottom line

• For most users, taking fluoxetine with fish oil is acceptable and commonly done. There is no established harmful interaction between fluoxetine and omega‑3 that causes serotonin syndrome. ^[2]
• The main shared concern is bleeding: fluoxetine can raise bleeding risk, and fish oil may add a small additional effect, especially if you also use NSAIDs or blood thinners so stay alert for bleeding signs and discuss with your clinician if you have risk factors. ^{[1] [3]}