Women who take the antidepressant Paxil along with the breast cancer drug tamoxifen may increase their risk of dying from the disease, Canadian doctors say.

But the doctors, who studied the health records of more than 2,400 women with breast cancer, stressed the importance of not stopping treatment suddenly.

The antidepressant paroxetine, which is sold under the brand name Paxil and various generic names, and tamoxifen, whose brand name is Nolvadex, each work when taken alone.

The study reported in this week's British Medical Journal found that women taking both paroxetine and tamoxifen lost the benefits of the cancer treatment. The risk of dying from breast cancer increased the longer both drugs were taken together.

Tamoxifen is widely used to treat breast cancer and may be taken for up to five years to prevent a recurrence. Paroxetine eases depression as well as the hot flashes that can occur after cancer treatment.

The researchers looked at the health records of 2,430 women taking tamoxifen from 1993 to 2005. About 25 per cent of the participants, or 630 women, were also taking paroxetine.

The findings suggested paroxetine interferes with the way tamoxifen works.

Stay with tamoxifen

"Tamoxifen is an extremely important drug for breast cancer," said Dr. David Juurlink, a co-author of the study and a scientist at the Institute for Clinical Evaluative Sciences in Toronto. Paroxtine "takes that benefit away by interfering with the body's normal handling of tamoxifen."

Juurlink said the study should not cause women to reconsider taking tamoxifen.

But he stressed that patients taking paroxetine and tamoxifen should not suddenly stop taking the antidepressant, because of the risks of withdrawal and worsening depression. The antidepressant has to be stopped gradually.

Paroxetine is in a class of antidepressants known as selective serotonin reuptake inhibitors or SSRIs. The researchers said paroxetine blocks or inhibits an enzyme called cytochrome P450 2D6, which is needed to metabolize tamoxifen into its active form.

The researchers did not find an increased risk of death from recurrent breast cancer among the smaller sample of women on tamoxifen who took other SSRIs, such as fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa) and venlafaxine (Effexor).

"If you need to be on an antidepressant with tamoxifen, there are choices, there are options out there that don't have the same risk," Juurlink said.

During the study period, 1,074 of the women died, including 374 from breast cancer, according to Ontario's cancer registry. The others died of other natural causes.

In a worst-case scenario, if patients took paroxetine the whole time that they were being treated with tamoxifen, the researchers said they would expect one additional death for every seven patients treated.

"Physicians should be aware that paroxetine and other strong 2D6-inhibiting drugs should be avoided in women treated with tamoxifen," Dr. Frank Andersohn, a senior research associate at the Institute for Social Medicine, Epidemiology, and Health Economics at Charité University Medical Center in Berlin, who wrote a journal editorial accompanying the study.

Unknown factors

The findings are "strongly suggestive," said Dr. Steven Narod, director of the Familial Breast Cancer Research Unit at Women's College Hospital in Toronto, adding Paxil indirectly increases risk.

Narod did not want people to misinterpret the findings, noting tamoxifen is extremely effective at reducing risk of recurrence in women with estrogen receptor-positive cancer.

Since the study looked back at health records, it is possible that things not known to the researchers may have interfered with the findings, or that some women didn't take their daily tamoxifen medication as prescribed, Dr. Karen Gelmon, an oncologist at the B.C. Cancer Agency, said in commenting on the study.

With files from The Canadian Press