Paroxetine taken alongside tamoxifen was linked to more breast cancer deaths; other SSRIs were not
In 2,430 Ontario women on tamoxifen and one SSRI, paroxetine overlap of 25, 50 and 75 percent of tamoxifen time was associated with 24, 54 and 91 percent higher risk of breast cancer death. Other antidepressants showed no such risk.
Well-supported by good-quality research. how we score evidence
Caveat on this rating: Observational; the paroxetine label (this wave) states that other studies have failed to find the risk. Women 66 and older only. The other-SSRI null result is reassuring but the study was not powered to rank them.
Tamoxifen is a prodrug: the liver enzyme CYP2D6 turns it into the compound that fights the cancer. Paroxetine is the strongest CYP2D6 blocker among the SSRIs. This study asked whether that chemistry shows up in survival.
Significant findings
Kelly and colleagues (BMJ, 2010) followed women in Ontario aged 66 or older treated with tamoxifen between 1993 and 2005 who had overlapping treatment with a single SSRI. "Of 2430 women treated with tamoxifen and a single SSRI, 374 (15.4%) died of breast cancer during follow-up (mean follow-up 2.38 years, SD 2.59)."
"After adjustment for age, duration of tamoxifen treatment, and other potential confounders, absolute increases of 25%, 50%, and 75% in the proportion of time on tamoxifen with overlapping use of paroxetine (an irreversible inhibitor of CYP2D6) were associated with 24%, 54%, and 91% increases in the risk of death from breast cancer, respectively (P<0.05 for each comparison). By contrast, no such risk was seen with other antidepressants."
The absolute estimate: "We estimate that use of paroxetine for 41% of tamoxifen treatment (the median overlap in our sample) would result in one additional breast cancer death within five years of cessation of tamoxifen for every 19.7 (95% confidence interval 12.5 to 46.3) patients so treated".
Worth asking
The paroxetine label now says, in section 5.11, that "other studies have failed to demonstrate such a risk" and tells prescribers to "consider using an alternative antidepressant with little or no CYP2D6 inhibition" when tamoxifen is used; that row is beside this one. The disagreement is real. What is not disputed is the mechanism and that alternatives exist. If you take tamoxifen and any antidepressant, the question is which enzyme it inhibits, and it is a question for the oncologist and the prescriber together, not for you to act on alone.
Source
Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study — Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, Paszat LF (2010)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1136/bmj.c693
DOI: 10.1136/bmj.c693
How this was scored
- Study design
- Cohort study
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 2,430
- Preregistered
- not recorded
- Conflicts disclosed
- Yes
- 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 "strong evidence". Well-supported by good-quality research. It scores 72 out of 100 on our published rubric. One caveat travels with that badge: Observational; the paroxetine label (this wave) states that other studies have failed to find the risk. Women 66 and older only. The other-SSRI null result is reassuring but the study was not powered to rank them. 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?
Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study — Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, Paszat LF (2010). Published in: Top-tier peer-reviewed journal. DOI: 10.1136/bmj.c693. 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: Cohort study. Funding: Independently 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.