The world of modern pharmacology has numerous instances of drugs showing unexpected therapeutic side effects that often lead to major breakthroughs in the treatment of serious conditions. The first-ever clinically approved antidepressant, Iproniazid, was originally developed as a treatment for tuberculosis.
When patients who were administered the drug during clinical trials reported a feeling of euphoria, it opened the doors to an entirely new class of drugs capable of treating conditions like depression, bipolar disorder, and drug addiction.
In recent years, antidepressants have even shown promise in the field of cancer research. According to the findings of a Swiss research team, Vortioxetine, a highly affordable antidepressant widely available in the market, showed remarkable efficacy in killing aggressive brain cancer cells.
You can read more about that story here. This article, in contrast, will take an altogether different tangent, looking at the cancer risk posed by antidepressants. The topic is well worth exploring, since the global consumption of antidepressants has more than doubled since 2000. But first a quick overview of the current landscape of antidepressants.
A Quick Look at the Different Types of Antidepressants
Iproniazid, discovered in the 1950s, belonged to the first generation of antidepressants called the Monoamine Oxidase Inhibitors (MAOIs). They had high risk of side effects and negative interactions with other medications and food items.
The second class of antidepressants, also discovered in the late 1950s, were called tricyclic antidepressants (TCAs). While they were safer than MAOIs, TCAs still posed high risk of toxic overdose and other health conditions, particularly with long-term use.
Discovered in the late 1970s, Selective Serotonin Reuptake Inhibitors (SSRIs) were much safer than their predecessors. Popular antidepressants like Prozac and Zoloft fall into this category. SSRIs are still among the most widely used antidepressants in the world as of 2024.
Even newer classes of antidepressants have been developed in the 1990s and 2000s. These include Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), Atypical Antidepressants, and Serotonin Modulators/Stimulators.
Correlation Between Antidepressant Use and Cancer Risk
There are at last three dozen different antidepressants in the market today. Since SSRIs and SNRIs are usually prescribed as the first-line treatments, the majority of cancer studies focus on the impact of these drugs.
Likewise, the four most common cancers in the world are breast cancers, lung cancers, bowel cancers, and prostate cancers. Due to their higher public health impact, data availability, and funding availability, research is often focused more on these cancers.
Breast Cancer in Women
Women are twice as likely to receive antidepressant prescriptions than men, according to an NHS-funded study in the UK. Breast cancer accounts for almost 30% of all cancers in women in the US. And breast cancer patients are routinely prescribed antidepressants during treatment to combat common issues of anxiety and depression.
Consequently, studies have explored the breast cancer risk posed by antidepressant use. Several lab studies involving animals and tumor cultures had suggested that certain SSRIs and TCAs may increase tumor risk either through mutation or by causing sex hormone imbalance.
However, a 2022 review of over 34 epidemiological studies between 1995 and 2021 involving over 160,000 breast and ovarian cancer patients concluded that there was no statistical correlation between antidepressant use and breast cancers.
Although they may pose no direct risk, certain antidepressants are known to hinder the action of Tamoxifen, a hormonal drug used to treat breast cancer in premenopausal women. “ASCO guidelines specifically mention that prescribers of Tamoxifen should have caution about using antidepressants that are CYP450-2D6 inhibitors,” says Dr. Donna Greenberg, Associate Professor of Psychiatry at Harvard.
Lung Cancers
Lung cancer remains the leading cause of cancer death across the world, with 125,000 lives lost in the US alone each year. While smoking and air pollution are leading risk factors, recent studies do suggest that certain classes of antidepressants may also have a role to play.
A 2023 meta-analysis of existing studies from the US, the UK, Finland, Hungary, and Taiwan showed an 11% increase in the risk of lung cancer from the use of SNRIs. Meanwhile, SSRIs and TCAs showed no increased cancer risk.
One possible reason suggested by the authors of the study is the DNA damage caused by SNRIs over long-term use, which can lead to mutations and cancer. However, further research is needed to validate this hypothesis. Meanwhile, this YouTube video provides an excellent short introduction to SNRIs.
Bowel Cancers
Bowel issues like constipation is a frequent side effect associated with many TCAs and some SSRI antidepressants. Perhaps rather paradoxically, studies have shown that regular use of SSRIs can reduce the risk of colorectal cancers by up to 30%.
One possible explanation for this is the role played by serotonin in suppressing cancer cells. Since SSRIs increase the availability of serotonin across the whole body, extended use of these drugs could have a secondary beneficial impact on the prevention of bowel cancers.
Unfortunately, the full role of serotonin in cancer genesis is still not properly understood. A 2023 study by a Chinese research team postulated that serotonin expression on specific receptors in the gut called 5-HT can promote the growth of tumors.
Implications for the Future of Cancer Treatments and Prevention
Antidepressant use in the developed world is at an all-time high. Since 2020, there has been a 64% increase in antidepressant prescriptions to young adults in the US alone. Long-term use of these drugs is also seeing a steady increase.
When millions of patients use a particular class of drugs, it is essential to look for any increase in cancer risk. Even a few percentage points could translate into thousands of excess cancer deaths.
It will not be easy, given the presence of multiple risk factors. For example, individuals who are on antidepressants can often have other traits that increase cancer risk, like smoking, alcoholism, or substance abuse.
For now, the general consensus is that there is not much evidence of excess cancer risk from the use of popular antidepressants. Will future research prove us wrong? Only time will tell.
