Antidepressants may trigger bacterial resistance to antibiotics, study finds

Australian researchers have discovered that antidepressants—drugs prescribed to millions for depression and anxiety—can push bacteria toward resistance against antibiotics, a finding that adds a new dimension to one of medicine's most pressing problems. The work, published January 23 in the Proceedings of the National Academy of Sciences, emerged from a decade-long puzzle that began when Jianhua Guo and his team at the University of Queensland noticed something counterintuitive: wastewater from residential neighborhoods contained more antibiotic-resistant bacteria than wastewater from hospitals, where antibiotics are used far more heavily. That observation prompted a question: what else might be driving resistance?

The answer, it turns out, may be sitting in medicine cabinets across the world. In 2018, Guo's lab published findings showing that fluoxetine—the antidepressant sold as Prozac—could cause E. coli to become resistant to multiple antibiotics. The latest study expands that work considerably, testing five additional antidepressants and tracking how E. coli developed resistance to thirteen different antibiotic drugs. What the researchers found was a mechanism: when bacteria are exposed to antidepressants in oxygen-rich environments, the drugs trigger the production of molecules toxic to the bacteria themselves. The bacteria respond by activating a pumping system designed to expel foreign substances. But here is the problem—while the bacteria are expelling those toxic molecules, they also expel antibiotic molecules, preventing the drugs from doing their job. The bacteria survive, and in surviving, they learn.

The resistance does not stop there. Exposure to antidepressants also increases the likelihood that bacteria will mutate, generating new drug-resistant genes. Even more concerning, prolonged exposure to antidepressants like sertraline can cause bacteria to transfer resistance genes to other bacteria, spreading the trait through entire microbial populations and even across different bacterial species. The mechanism is straightforward in the lab, but the human body is more complex. E. coli thrives in low-oxygen environments like the gut, and the researchers found that antibiotic resistance develops more slowly under anaerobic conditions. This suggests that resistance might take longer to develop inside a person taking antidepressants than it does in a petri dish—but prolonged use could still enable it.

The scale of the problem is difficult to overstate. According to the Lancet, approximately 1.27 million deaths globally in 2019 were attributed to bacterial antimicrobial resistance. Diseases once considered routine—tuberculosis, pneumonia, gonorrhea—are becoming harder to treat as bacteria develop defenses against standard antibiotics. The discovery that non-antibiotic drugs might be accelerating this process complicates an already dire public health landscape. Yet the researchers are careful to note that their findings are not a reason for people to stop taking antidepressants. The work is still preliminary, conducted in laboratory conditions that do not fully replicate the human body.

To bridge that gap, Guo's team is now testing the mechanism in animal models—specifically, mice being administered antidepressants—to see whether the resistance develops in living organisms the way it does in culture. These studies will help determine whether the laboratory findings translate to clinical reality and, if they do, what that means for the millions of people who depend on antidepressants for their mental health. The question now is not whether to stop taking these drugs, but how to use them safely while the science catches up to the reality of their effects on the bacteria living inside us.