Friday, June 5, 2009

SSRIs and Tamoxifen: Does the Combination Increase Recurrence?

Prozac Linked to Suicide Attempts and Violence

As recently reported by CTV: {excerpts from the article; data presented at ASCO May 31/09}

ORLANDO, Fla. — Breast cancer survivors risk having their disease come back if
they use certain antidepressants while also taking the cancer prevention drug
tamoxifen, worrisome new research shows...The new study, reported Saturday at a
cancer conference in Florida (ASCO), is the largest to look at the issue. It found that
using these interfering drugs -- including Prozac, Paxil or Zoloft -- can
virtually wipe out the benefit tamoxifen provides...Breast cancer recurred in
about seven per cent of women on tamoxifen alone, and in 14 per cent of women
also taking other drugs that could interfere -- mainly the antidepressants Paxil
and Prozac, and, to a lesser extent, Zoloft...No greater breast cancer risk was
seen in women taking the antidepressants Celexa, Lexapro or Luvox with
tamoxifen, and there are reasons to think that other antidepressants may be safe
as well, Epstein said..."This is a very controversial area," said Dr. Claudine
Isaacs, a breast specialist at Georgetown University's Lombardi Comprehensive
Cancer Center. "Until these data are absolutely clear, I would avoid drugs that
impact on tamoxifen metabolism."

From OncocologySTAT:
"SRIs, however, can also inhibit the 2D6 enzyme that converts tamoxifen to its
main active metabolite, endoxifen, thus possibly decreasing its efficacy."

Massachusetts General Hospital Centre For Women's Health posted an article in June '08 regarding interactions between tamoxifen and antidepressants. I discovered this post when searching for solutions after detecting the interaction via Micromedex/Lexicomp.
{Click here for link to article}.

The following table from the above mentioned article provides some guidance when faced with such a dilemma:

CPY2D6 Inhibitors

Strong Inhibitors (Should be avoided if


Moderate Inhibitors:

Weak Inhibitors (Use not restricted by treatment with


If antidepressants are indicated in the treatment of a woman currently
taking tamoxifen, the following treatment recommendations have been made:
*If possible, avoid antidepressants, including fluoxetine and paroxetine, that are
strong inhibitors of the CPY2D6 enzyme (see the list of inhibitors above)
*If the antidepressant is being used solely for the management of hot
flushes, other agents, such as gabapentin, may be used instead
*If it is not possible to avoid these antidepressants, another option for postmenopausal women
only would be to switch from tamoxifen to an aromatase inhibitor, if medically

Please post your comments below or email me at:

* Thanks to Scott Edwards, PharmD for the link to the CTV News article.


Christopher (Chris) Ralph June 8, 2009 at 3:35 PM  

I posed the question of how to proceed with respect to this interaction to a medical oncologist here who is a member of the breast ca tumor group. His response was that he looks at each patient and the situation individually.
- If the intention is to treat hot flashes, than gabapentin or venlafaxine would be 1st line.
- If the patient is being treated for a psychiatric illnes and is on one of the potentially problematic medications (for instance, paroxetine or fluoxetine) but could theoretically be managed by another medication, he would alert the family GP or prescribing MD.
- If it was a patient that has a history of depression and tried on multiple agents and now stable with fluoxetine or paroxetine, he would be hesitant to change.

Christopher (Chris) Ralph February 12, 2010 at 10:13 AM  

Paroxetine Blocks the Beneficial Effects of Tamoxifen in Breast Cancer
LONDON -- February 10, 2010 -- Women with breast cancer who take the antidepressant paroxetine at the same time as tamoxifen are at an increased risk of death, concluded a study published in the British Medical Journal.


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Pharmacy History

"The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.
Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.[3]

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article."

From Wikipedia:

Journal of Palliative Medicine - Table of Contents

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