Paxil Blocks Tamoxifen, Lowers Survival Odds Against Breast Cancer

21 feb 2010-- Women with breast cancer who take both tamoxifen and the antidepressant Paxil may increase their risk of dying because Paxil reduces tamoxifen's effectiveness, Canadian researchers report.


"Paxil can deprive women of the benefit of tamoxifen, especially when it is used in combination with tamoxifen for a long time," said lead researcher Dr. David Juurlink, division head of clinical pharmacology and toxicology at Sunnybrook Health Sciences Center in Toronto.


"Patients who are on tamoxifen and who require an antidepressant should probably be given something different," he added.


Paroxetine (Paxil) is a selective serotonin reuptake inhibitor (SSRI) that significantly inhibits an enzyme called cytochrome P450 2D6, which is needed to metabolize tamoxifen into its active form. But this dampening effect was not seen with certain other SSRIs evaluated, including citalopram (Celexa) and venlafaxine (Effexor), the researchers said.


Patients taking Paxil and tamoxifen should talk with their doctors about changing their antidepressant, Juurlink said.


But he advised against abruptly discontinuing Paxil.


"There is a very real danger to stopping Paxil suddenly. There is a well-described withdrawal syndrome and the risk of depression becoming more severe," he said.


In addition, any transition to another antidepressant should be done gradually over several weeks, he said.


The report is published in the Feb. 8 online edition of the British Medical Journal.


For the study, Juurlink's group looked at the medical records of 2,430 women with breast cancer who began taking tamoxifen between 1993 and 2005. About 30 percent of the women were also taking an antidepressant, Paxil being the most common. Antidepressants are often prescribed to reduce hot flashes associated with tamoxifen in addition to easing symptoms of depression.


Paxil plus tamoxifen was linked to an increased risk of dying from breast cancer, and the risk increased with the amount of time the drugs were taken together, the researchers found.


Taking Paxil for 41 percent of the time that tamoxifen was also taken resulted in one extra death from breast cancer within five years of stopping tamoxifen among every 20 women taking the drugs simultaneously, Juurlink's team estimated. The more time the drugs were taken together, the greater the risk, they added.


SSRIs inhibit CYP 2D6 to varying degrees, the authors said, noting Paxil is "exceptionally potent" in that respect.


Dr. Frank Andersohn, a senior research associate at the Institute for Social Medicine, Epidemiology, and Health Economics at Charite University Medical Center in Berlin, Germany, and author of an accompanying journal editorial, said that "physicians should be aware that paroxetine and other strong 2D6-inhibiting drugs should be avoided in women treated with tamoxifen."


Fluoxetine (Prozac) is also a strong 2D6 inhibitor, the authors noted.


Another expert, Dr. Harold J. Burstein, said this paper adds to the substantial literature suggesting that drugs that affect the metabolism of tamoxifen might affect breast cancer outcomes for women taking tamoxifen.


"While the results should not alarm patients currently taking SSRIs, they do suggest that, as a practice style, patients on tamoxifen who also need SSRIs should probably seek out agents such as Effexor in preference to Prozac or Paxil," said Burstein, clinical investigator in the breast oncology center at Dana-Farber Cancer Institute, Brigham and Women's Hospital in Boston.


"The findings are also a reminder that each drug that a patient takes should be thought through carefully. If there are drugs that aren't needed, then they aren't needed and can be omitted," he added.