Recent research has uncovered a surprising new role for fluoxetine, commonly known as Prozac. While widely prescribed as an antidepressant, this medication may also provide protection against infections and life-threatening sepsis. Scientists have identified its antimicrobial properties and its ability to modulate immune responses, potentially reducing tissue and organ damage.

Studies conducted on mice demonstrated that fluoxetine effectively lowered bacterial levels, increased anti-inflammatory molecules, and prevented dangerous immune overreactions. Notably, these protective effects occurred independently of serotonin, the neurotransmitter primarily targeted by the drug in its traditional role as an antidepressant.

Key Findings:

• Dual Protection: Fluoxetine not only kills bacteria but also helps regulate the immune response.
• Sepsis Defense: Mice treated with fluoxetine exhibited lower bacterial loads and a greater likelihood of survival.
• Serotonin Independence: The drug’s immune-modulating effects function separately from its influence on serotonin.

Expanding the Understanding of SSRIs in Disease Management

Beyond its well-established use in mental health treatment, fluoxetine may hold promise in combating severe infections. Scientists at the Salk Institute have explored how this drug interacts with the immune system, findings that could lead to novel therapeutic approaches for infectious diseases. This discovery comes at a critical time when innovative treatments are needed to enhance preparedness for future pandemics.

Additional studies have indicated that individuals taking selective serotonin reuptake inhibitors (SSRIs) like Prozac experienced less severe COVID-19 infections and a reduced risk of developing long COVID. In another study, fluoxetine was found to protect mice from sepsis—a condition where an excessive immune response to infection can result in organ failure or death.

By uncovering the mechanisms behind fluoxetine’s unexpected immune-boosting properties, researchers have paved the way for potential clinical trials exploring its use in infection and immune disorder treatments. These findings were published in Science Advances on February 14, 2025.

“When treating an infection, the optimal treatment strategy would be one that kills the bacteria or virus while also protecting our tissues and organs,” explains Professor Janelle Ayres, holder of the Salk Institute Legacy Chair and Howard Hughes Medical Institute Investigator.

“Most medications we have in our toolbox kill pathogens, but we were thrilled to find that fluoxetine can protect tissues and organs, too. It’s essentially playing offense and defense, which is ideal, and especially exciting to see in a drug that we already know is safe to use in humans.”

Addressing the Dangers of Sepsis

The immune system serves as the body’s primary defense against infections, but in conditions such as sepsis, it can become overactive, causing widespread inflammation and damaging the body’s own tissues. Severe COVID-19 cases have shown similar immune overreactions, further highlighting the need for treatments that balance immune responses without compromising the body’s ability to fight infections.

While suppressing inflammation might seem like a solution, doing so can leave patients vulnerable to infections. Immunosuppressive drugs must be carefully timed, as they are most effective before significant tissue damage occurs. Ideally, an effective treatment would manage immune response intensity while simultaneously targeting the infection itself.

How Fluoxetine May Help

To better understand fluoxetine’s potential in this regard, researchers studied two groups of mice infected with bacteria—one group pretreated with fluoxetine and the other left untreated.

Mice that received fluoxetine showed significantly lower bacterial levels within eight hours of infection, suggesting that the drug possesses antimicrobial properties that inhibit bacterial growth. Additionally, higher levels of the anti-inflammatory molecule IL-10 were detected in these mice, which played a crucial role in preventing sepsis-induced metabolic disturbances and protecting vital organs.

By distinguishing fluoxetine’s antimicrobial action from its immune-regulating effects, the researchers demonstrated that the drug offers a dual benefit—actively combating pathogens while also reducing immune-related damage.

Fluoxetine’s Effects Beyond Serotonin

To determine whether fluoxetine’s protective effects were linked to serotonin, researchers examined two additional groups of mice: both were pretreated with fluoxetine, but only one retained normal serotonin levels.

Surprisingly, fluoxetine provided the same infection-fighting benefits regardless of serotonin presence, confirming that its positive effects stemmed from a separate mechanism.

“That was really unexpected, but also really exciting,” says Robert Gallant, the study’s first author and a former graduate student researcher in Ayres’ lab.

“Knowing fluoxetine can regulate the immune response, protect the body from infection, and have an antimicrobial effect—all entirely independent from circulating serotonin—is a huge step toward developing new solutions for life-threatening infections and illnesses. It also really goes to show how much more there is to learn about SSRIs.”

Looking Toward the Future

Building on these promising findings, researchers now aim to determine appropriate fluoxetine dosages for treating sepsis in humans. Additionally, they plan to investigate whether other SSRIs exhibit similar protective effects.

“Fluoxetine, one of the most prescribed drugs in the United States, is promoting cooperation between host and pathogen to defend against infection-induced disease and mortality,” says Ayres. “Finding dual protective and defensive effects in a repurposed drug is really exciting.”

Research and Funding

This study was conducted with contributions from Karina Sanchez, Emeline Joulia, and Christian Metallo of the Salk Institute, along with Jessica Snyder of the University of Washington.

The research was supported by funding from the National Institutes of Health (DPI AI144249, R01 AI14929, F31 AI169988, T32 GM007240-43, T32 GM133351, NCI CCSG: P30CA014195) and the NOMIS Foundation.

As investigations continue, fluoxetine’s unexpected benefits may redefine how infections and immune disorders are treated, offering new hope for patients worldwide.