Tamoxifen and antidepressants that inhibit CYP2D6: what to ask your team

Tamoxifen is used in hormone receptor-positive breast cancer to lower the chance of recurrence, and sometimes to reduce risk in people at high risk. It is usually taken for years. Common effects include hot flushes, vaginal discharge, fluid retention and nausea, as Macmillan describes, and mood changes are reported by some people.

Our guide on hormone receptor-positive breast cancer describes where tamoxifen fits into treatment. Because treatment is long, a new medicine such as an antidepressant is a common scenario.

Pharmacology references describe tamoxifen as being converted in the liver into more active forms, with an enzyme called CYP2D6 playing a major part. Some antidepressants, including paroxetine and fluoxetine, are strong inhibitors of that enzyme. If the conversion is reduced, the amount of active tamoxifen might fall.

The clinical importance of this effect has been debated, and we did not retrieve a UK source quantifying it. What UK sources do show is that the NHS paroxetine page names tamoxifen among medicines that may not mix well, which is why prescribers take it seriously.

The NHS paroxetine page names tamoxifen. The NHS venlafaxine page we read lists anticoagulants, NSAIDs and MAOIs but does not name tamoxifen, and the citalopram and sertraline pages we read do not list it either. That pattern suggests the prescriber has choices among antidepressants.

Never assume a particular antidepressant is safe or unsafe on the strength of a web page. Ask the prescriber or pharmacist to check the combination, because lists change and individual circumstances differ.

• Paroxetine: named by the NHS as interacting with tamoxifen.

• Fluoxetine: discussed in pharmacology texts as a strong CYP2D6 inhibitor.

• Venlafaxine, citalopram, sertraline: tamoxifen not named on the NHS pages we read.

MedlinePlus says to tell your doctor if you take warfarin, cyclophosphamide, anastrozole, letrozole, bromocriptine, medroxyprogesterone, aminoglutethimide, phenobarbital or rifampin, and that doses may need changing or monitoring. Enzyme inducers such as rifampin may lower tamoxifen exposure, as our enzyme-inducer guide explains.

Cancer Research UK notes that cancer drugs can interact with medicines, herbal products and some food and drinks, and mentions grapefruit juice as an example that can increase side effects. It advises telling the healthcare team about vitamins, herbal supplements and over-the-counter remedies.

Low mood, anxiety and hot flushes are common with hormone therapy and deserve treatment. Talk to the breast care nurse, oncologist or GP about options, including non-drug approaches and talking therapies. The aim is for treatment of mood to be chosen with tamoxifen in mind.

Do not self-treat with St John's wort without checking, as the NHS lists it among herbal products that interact with many medicines.

Do not stop either medicine suddenly. Contact your breast care team or GP to review the combination, and the pharmacist can flag it on your records. Macmillan says to contact your hospital for concerning symptoms; MedlinePlus advises telling all your doctors and providers that you take tamoxifen.

Seek urgent help for signs of a blood clot, such as a swollen painful leg or sudden breathlessness, and for abnormal vaginal bleeding, as these are known concerns with tamoxifen and are described by Macmillan.