Possible Link Between SSRIs and Breast, Ovarian Cancer

But Expert Says Results Should Be Interpreted With Caution

Fran Lowry

April 14, 2011

April 14, 2011 — A meta-analysis of 61 studies that looked at the relationship between cancer and antidepressant use shows a "small but statistically significant" increase in the risk for breast and ovarian cancer in women who use selective serotonin reuptake inhibitors (SSRIs).

A meta-analysis has its limitations, but still I feel that these results tell us that we really need to study further the use of SSRIs in women and the link to cancer. It's a fascinating question that really begs an answer.

"A meta-analysis has its limitations, but still I feel that these results tell us that we really need to study further the use of SSRIs in women and the link to cancer," lead study author, Lisa Cosgrove, PhD, of the Edmond J. Safra Center for Ethics, Harvard University, Boston, Massachusetts, told Medscape Medical News. "It's a fascinating question that really begs an answer."

But Jennifer Payne, MD, director of the Women's Mood Disorders Center at Johns Hopkins School of Medicine, Baltimore, Maryland, cautions that the study has limitations and may mislead women into abandoning their antidepressant therapy out of undue fears that they are at increased risk for cancer.

Dr. Jennifer Payne

In the study, which was published online April 6 in PLoS ONE, Dr. Cosgrove and colleagues examined the potential association between tricyclic antidepressants (TCAs) or SSRIs and cancer in 35 preclinical and 26 epidemiologic studies.

They found that 10 (28.6%) of the preclinical studies reported that an antidepressant agent was carcinogenic, a tumor promoter, or genotoxic and that 10 (38.4%) of the epidemiologic studies reported an association between the use of these antidepressants and cancer.

Strongest Link to SSRIs

The pooled odds ratio (OR) for this association in the epidemiologic studies was 1.11 (95% confidence interval [CI], 1.03 – 1.20). Looking at TCA use only, the OR was lower (OR, 1.05; 95% CI, 0.98 – 1.14). The OR for SSRIs was 1.07 (95% CI, 0.99 – 1.51). Moreover, all studies except one that were included in the SSRI analysis reported a positive association, Dr. Cosgrove pointed out.

Dr. Lisa Cosgrove

"When we looked at the older antidepressants, the TCAs, the data for the TCAs were all over the map — some had negative findings, some had positive findings, but when you look at the SSRIs, there's 1 study that did not find a positive association. I think that's a startling finding from the subanalysis. At the very least, it yells at you that we need more research on this," she said.

The study also found that researchers with industry affiliations were significantly less likely than researchers without industry ties to conclude that antidepressants increase the risk for breast or ovarian cancer, Dr. Cosgrove noted.

"There was a statistically significant relationship between researchers' industry ties and conclusions regarding antidepressants and cancer, with a P value as per 2-sided Fisher's exact test equal to .0012," she said.

Don't Ignore the Outlier

According to Dr. Payne, 1 study that did not find a positive association between antidepressant use and cancer was a very large epidemiologic study of more than 39,000 patients by Dalton et al (Epidemiology. 2000;11:171-176).

This was a population-based cohort study that estimated the incidence of cancer after antidepressant treatment in 39,807 adults living in Denmark between 1989 and 1995 from data obtained from the Danish Cancer Registry.

The study authors concluded that there was little evidence that antidepressants promote cancer, except for a possible effect of TCAs and tetracyclic antidepressants on non-Hodgkin's lymphoma.

If you take women who have the same stage of breast cancer, and half have depression and the other half do not, the women with depression have twice the rate of death...That's enormous. That is so much bigger than the small increased risk shown in this study.

"This study was huge. It's the kind of epidemiological study that you want to answer a question like this. The odds ratio was 1, meaning there was no association for the SSRIs with cancer. I would like to delve into the other studies that were positive to see how big they were, but the biggest one, the one that carries the most weight, showed no association with cancer," said Dr. Payne.

She added she is concerned that women with cancer who are depressed might choose not to take antidepressant medications because of studies such as this one.

"If you take women who have the same stage of breast cancer, and half have depression and the other half do not, the women with depression have twice the rate of death, even if their cancer is the same stage, and they are the same age and matched for other risk factors. Twice the rate of death. That's enormous. That is so much bigger than the small increased risk shown in this study."

Dr. Cosgrove has reported no relevant financial interests. Dr. Payne reports that she receives grant support from Stanley Medical Research Institute, Repligen Inc, and the National Institutes of Health and has served as a consultant for Pfizer and Astra Zeneca.

PLoS ONE. Published online April 6, 2011.

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