Depression, antidepressants and cancer: A personal perspective

Over the years, there have been contradictory studies assessing a link between depression and an increased risk of cancer. For example, after following 3,117 Baltimore-area subjects for 24 years, Johns Hopkins researchers reported that the overall cancer risk was doubled in individuals suffering from major depression, while the rate of breast cancer in depressed women was four times higher than expected. In contrast, the Alameda County (California) Study, which followed 6,848 people for 17 years, found no evidence that depression increased cancer rates or cancer mortality in either sex.

One way of trying to make sense out of conflicting findings, is to perform what is called a meta-analysis of all the results. Applying this approach to 13 published studies, statisticians in Belgium and the Netherlands found an overall 12% increased risk of cancer among depressed patients. Similar to the Baltimore study, they observed a specific effect of chronic depression on breast cancer; women who reported being depressed for 10 or more years had a 2.5-fold increased risk of developing the disease. A new twist to this possible association occurred quite by accident in 1989, when I observed that a novel tamoxifen-like antihistamine , abbreviated DPPE, stimulated the growth of experimental malignant tumours, including breast cancer, in laboratory mice and rats.

In addition to being unexpected, the finding was potentially alarming because my tests also showed that other drugs, such as the “SSRI” -type antidepressant, fluoxetine (Prozac), shared similar chemical and biological properties with DPPE. Could fluoxetine also stimulate cancer to grow? Subsequent experiments, carried out in collaboration with my University of Saskatchewan colleague, Dr. Rob Warrington , showed that both fluoxetine, and an older tricyclic antidepressant , amitriptyline, mimicked DPPE to stimulate melanoma and breast cancer growth in rodents. Since the drug doses we used in the rodents were equivalent to those taken by humans, our findings, published in the journal, Cancer Research, were also widely, and sometimes sensationally, reported in the press. 

Soon after, in a letter published in the American Journal of Epidemiology, I urged scientists to “examine the possibility that the drugs used to treat depression, rather than the depression itself, may, in certain circumstances, influence the course or development of human cancer.” They listened. In the years that followed, many studies were published; some said “yes”, while others said “no”. Over time, with no definitive answer forthcoming, the issue slowly drifted to the back burner… that is, until now.

In a just-published meta-analysis of 26 epidemiology studies looking at an association between antidepressant drugs and cancer, Harvard University researchers, led by Dr. Lisa Cosgrove, found, on average, an 11% (range: 3 to 20%) increase in breast and ovarian cancer in users of antidepressants; the cancer risk was higher for users of SSRI antidepressants (7% increase) than users of the older tricyclic drugs (4% increase). But that was not all. Noting that “previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favourable study conclusions”, the Harvard group investigated the principal author of each epidemiological study to determine whether he or she had big pharma associations (such as receiving research funds, or payment for giving presentations, or acting as a company consultant).

The result? “Of the 22 studies for which the PI [principal investigator] had no industry ties, 42% (10/22) reported positive findings.” However, “none of the 4 epidemiological studies for which the PI had industry ties reported a positive association between AD [antidepressant] use and cancer.” This disparity led Dr. Cosgrove and her colleagues to conclude that “the generic risk incurred by financial conflicts of interest undermines public trust…we need to develop mechanisms and policies that enhance public trust in the biomedical field (e.g. by creating “firewalls” between industry and academic researchers).”

What does all of this mean to people taking SSRIs and older, tricyclic, antidepressants? Has the link between these drugs and an increased risk of cancer, especially of the breast or ovary, been proven by the meta-analysis? No.

Has the level of concern once again increased? In my opinion, yes. After all, in the United States alone, over 20 million women take antidepressants. Even a small (e.g. 5%) increased risk of breast cancer among users of antidepressants could translate into 100,000 additional cases per year, ten times higher than the increase related to taking hormonal replacement therapy (HRT) in the menopause. To answer the question once and for all, based on the Harvard study findings it is clear that we need researchers without industry ties to conduct large new prospective studies. That said, an alternative might be to tap into a large pre-existing database, such as that of the Women’s Health Initiative (WHI) study.

In addition to definitively proving that HRT increases the risk of breast cancer, the WHI study has also carefully recorded the use of antidepressants, linking them to a 45% higher rate of strokes and 32% higher mortality rate from all causes. Could analysts assess the cancer risk in these same individuals?

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