The U.S. Centers for Disease Control and Prevention (CDC) estimates that one in eight U.S. adults takes an antidepressant, though this is based on data through 2018. As The New York Times reports, other sources estimate that antidepressant use jumped nearly 19 percent during the COVID pandemic of 2020. Either way, this represents millions of Americans, so much so that the SSRIs Zoloft and Lexapro represent the 12th and 15th most commonly prescribed medications in the country.
With this in mind, a groundbreaking new study suggests that SSRIs could help the immune system fight cancer.
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What are SSRIs?
Selective serotonin reuptake inhibitors, or SSRIs, are the type of antidepressant most commonly prescribed in the U.S. since they usually present fewer and less severe side effects.
Generally speaking, SSRIs work by increasing the amount of serotonin, a neurotransmitter that influences mood, in your brain.
"After serotonin has carried its message, nerve cells in your brain usually reabsorb the serotonin (known as reuptake)," explains Cleveland Clinic. "As its name—selective serotonin reuptake inhibitors— suggests, SSRIs work by blocking (inhibiting) reuptake."
The most common SSRIs are:
- Citalopram (Celexa)
- Escitalopram (Lexapro)
- Fluoxetine (Prozac)
- Paroxetine (Paxil)
- Sertraline (Zoloft)
- Vilazodone (Viibryd)
Why are SSRIs being studied in relation to cancer?
A new study published in the journal Cell looked at how SSRIs interact with T Cells, or immune cells, in both mouse and human tumor models.
The researchers began their journey in 2021, when a previous study showed that T cells produce the protein MAO-A upon recognizing cancer. MAO-A breaks down neurotransmitters, including serotonin, norepinephrine, and dopamine. However, when the researchers treated mice with melanoma and colon cancer using MAO inhibitors, or MAOIs, T cells were able to better attack tumors, according to a press release.
MAOIs were the first class of antidepressant drugs invented, but they're rarely prescribed today due to dietary restrictions, side effects, and safety concerns, notes Cleveland Clinic.
Therefore, the researchers turned their attention to SERT, a different protein that transports serotonin.
"Unlike MAO-A, which breaks down multiple neurotransmitters, SERT has one job—to transport serotonin," explained first study author Bo Li, PhD, a senior research scientist at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. "SERT made for an especially attractive target because the drugs that act on it—SSRIs—are widely used with minimal side effects."
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How do SSRIs target cancer?
To arrive at their findings, the researchers tested the effect of SSRIs in mouse and human tumor models for melanoma, breast, prostate, colon, and bladder cancers.
SSRI treatment reduced average tumor size by over 50 percent and enabled T cells to be more effective at killing cancer cells.
"SSRIs made the killer T cells happier in the otherwise oppressive tumor environment by increasing their access to serotonin signals, reinvigorating them to fight and kill cancer cells," said fellow senior study author Lili Yang, PhD, who runs the Yang Engineering Immunity Lab at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
Even more striking were the results when the researchers combined SSRI treatment with ICB therapy, which works "by blocking immune checkpoint molecules that normally suppress immune cell activity, allowing T cells to attack tumors more effectively," explains the press release.
In these cases, tumor size was reduced in all treated mice, even resulting in complete remission in some cases.
"Immune checkpoint blockades are effective in fewer than 25% of patients," said James Elsten-Brown, a graduate student in the Yang lab and co-author of the study. "If a safe, widely available drug like an SSRI could make these therapies more effective, it would be hugely impactful."
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What's next?
Next, the research team plans to confirm its findings in clinical trials involving cancer patients.
"Since around 20% of cancer patients take antidepressants—most commonly SSRIs—we see a unique opportunity to explore how these drugs might improve cancer outcomes," concluded Yang. "Our goal is to design a clinical trial to compare treatment outcomes between cancer patients who take these medications and those who do not."
