The paroxetine label carries the tamoxifen warning, the counter-evidence, and a contraindication with two antipsychotics
Paxil CR's label: tamoxifen's efficacy "may be reduced with concomitant use of paroxetine," though "other studies have failed to demonstrate such a risk"; paroxetine is contraindicated with thioridazine and pimozide over QT prolongation.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: The label itself records both directions on tamoxifen. The Kelly 2010 row in this wave is the study that found the risk.
A label is where the regulator and the manufacturer record what they accept about an interaction. On tamoxifen, this one records the dispute.
Significant findings
PAXIL CR prescribing information (Apotex, September 2025), section 5.11, Reduction of Efficacy of Tamoxifen: "Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer relapse/mortality, may be reduced with concomitant use of paroxetine as a result of paroxetine's irreversible inhibition of CYP2D6 and lower blood levels of tamoxifen. One study suggests that the risk may increase with longer duration of coadministration. However, other studies have failed to demonstrate such a risk. When tamoxifen is used for the treatment or prevention of breast cancer, prescribers should consider using an alternative antidepressant with little or no CYP2D6 inhibition."
Section 5.3, Drug Interactions Leading to QT Prolongation: "The CYP2D6 inhibitory properties of paroxetine can elevate plasma levels of thioridazine and pimozide. Since thioridazine and pimozide given alone produce prolongation of the QTc interval and increase the risk of serious ventricular arrhythmias, the use of PAXIL CR is contraindicated in combination with thioridazine and pimozide".
The patient counselling section lists the serotonin syndrome partners in the same words as the other SSRI labels: "triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, St. John's Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid)."
Worth asking
Paroxetine's distinguishing interaction is CYP2D6: it blocks the enzyme irreversibly, which is why the tamoxifen and antipsychotic warnings are on this label and not, in the same form, on sertraline's or citalopram's. Other CYP2D6-dependent drugs include some beta blockers, codeine and tramadol. If you take paroxetine, the question for a pharmacist is which of your other drugs are metabolised by CYP2D6.
Source
PAXIL CR (paroxetine hydrochloride) extended-release tablets: FDA-approved prescribing information, Warnings and Precautions 5.3 and 5.11, Drug Interactions 7.1 — Apotex Corp; US Food and Drug Administration (2025)
Regulator or national health body
How this was scored
- Study design
- Regulatory safety determination
- Funding
- Industry funded
- Published in
- Regulator or national health body
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 57 out of 100 on our published rubric. One caveat travels with that badge: The label itself records both directions on tamoxifen. The Kelly 2010 row in this wave is the study that found the risk. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
PAXIL CR (paroxetine hydrochloride) extended-release tablets: FDA-approved prescribing information, Warnings and Precautions 5.3 and 5.11, Drug Interactions 7.1 — Apotex Corp; US Food and Drug Administration (2025). Published in: Regulator or national health body. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Regulatory safety determination. Funding: Industry funded. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.