Prozac: A Potential Game Changer in the Battle Against Infections and Sepsis

Overview: Recent studies indicate that fluoxetine, a well-known antidepressant, may offer protection against infections and sepsis. Researchers have identified its antimicrobial properties and its role in modulating the immune response, which helps mitigate tissue and organ damage.

In experiments conducted on mice, fluoxetine demonstrated a significant reduction in bacterial levels, elevated anti-inflammatory molecules, and a prevention of dangerous immune overreactions. Interestingly, these protective effects were found to function independently of fluoxetine’s established impact on serotonin levels.

This combined capability of eradicating pathogens while safeguarding the body’s tissues opens up new avenues for infection treatment. The study emphasizes the potential of fluoxetine and similar selective serotonin reuptake inhibitors (SSRIs) as innovative strategies for managing infectious diseases.

Key Highlights

Dual Action: Fluoxetine effectively eliminates bacteria while also inhibiting excessive immune responses.
Protection Against Sepsis: Mice administered fluoxetine exhibited reduced bacterial infection and improved survival rates.
Independent of Serotonin: The immune-enhancing benefits of fluoxetine were not linked to its traditional serotonin-modulating effects.

Source: Salk Institute

While antidepressants like Prozac are primarily used to address mental health issues, groundbreaking research now suggests they may also offer defense against severe infections such as sepsis.

Scientists at the Salk Institute have unveiled how these medications can enhance immune function and counteract infectious diseases—findings that could pave the way for breakthrough treatments and improve global readiness for future health crises.

Illustration showing a brain. — Researchers Ayres and Gallant are set to investigate fluoxetine dosing strategies tailored for septic patients. Credit: Neuroscience News

The Salk Institute study aligns with earlier research indicating that individuals using SSRIs like Prozac experienced milder COVID-19 symptoms and a reduced incidence of long COVID.

Another investigation showed that fluoxetine effectively shielded mice from sepsis, a critical condition characterized by an overwhelming immune response leading to multi-organ failure or mortality.

By clarifying the mechanisms behind fluoxetine’s unexpected immune-boosting properties, the research team has brought fluoxetine and potentially other SSRIs closer to clinical applications in combating infections and immune disorders.

The new findings were published in Science Advances on February 14, 2025.

“The ideal treatment for infection would ideally eliminate the pathogen while also safeguarding our tissues and organs,” explains Professor Janelle Ayres, who holds the Salk Institute Legacy Chair and is an investigator at the Howard Hughes Medical Institute.

“While existing medications mainly target pathogens, we discovered that fluoxetine also protects bodily tissues and organs. This gives it a unique edge in playing both offensive and defensive roles, making it particularly exciting given its established safety profile in humans,” Ayres adds.

Although our immune systems strive to defend us against infections, they can occasionally become overactive. In cases of sepsis, this rampant inflammatory response can inflict profound damage to the body’s own tissues and organs. The same hyperactive response can also be seen in severe COVID-19 cases.

A straightforward solution might appear to involve dampening the inflammatory reaction; however, this approach could unwittingly heighten patient vulnerability to the initial infection as well as new threats.

Timing plays a crucial role here, as immunosuppressive therapies must be administered before any tissue damage occurs.

Instead, an optimal therapeutic approach should 1) proactively regulate the severity and duration of the immune response to inhibit bodily harm, and 2) address the infection responsible for the body’s compromised state.

To explore what role SSRIs might play in this context, researchers monitored mice with bacterial infections, dividing them into two groups: one group received fluoxetine treatment prior to exposure, while the other did not.

Remarkably, mice treated with fluoxetine exhibited protection against sepsis and multi-organ damage, as well as improved survival rates. The team then conducted a series of follow-up studies to unravel these effects.

Initially, they assessed bacterial counts in both groups of mice eight hours post-infection. Those treated with fluoxetine showed significantly fewer bacteria, indicating a less severe infection.

This observation confirmed that fluoxetine possesses antimicrobial qualities that help restrict bacterial growth.

Subsequently, the researchers analyzed levels of various inflammatory molecules in each group. They found increased amounts of anti-inflammatory IL-10 in the fluoxetine-pretreated mice, which appeared to prevent sepsis-induced hypertriglyceridemia, thus aiding the heart in maintaining its optimal metabolic state and protecting against infection-related health complications.

The researchers were able to separate the dual functions of fluoxetine—its antimicrobial action and the IL-10 mediated protection against tissue damage and mortality—highlighting its potential as both a pathogen killer and an immune system protector.

To observe whether fluoxetine’s interaction with serotonin contributed to its protective effects, the team included two additional mouse groups: both were pretreated with fluoxetine, but one had circulating serotonin, while the other did not.

Circulating serotonin, a crucial chemical messenger, regulates various bodily functions, including mood and pain, and is the primary target of fluoxetine’s impact on mental health.

The results revealed that fluoxetine’s beneficial health outcomes were completely independent of circulating serotonin—both mouse groups enjoyed similar protective benefits against infections.

“This was an unexpected and thrilling discovery,” states Robert Gallant, the study’s lead author and a former graduate student in Ayres’ lab. “Understanding that fluoxetine can enhance immune response and provide antimicrobial effects, entirely independent of serotonin, marks a significant advancement in developing new treatments for severe infections and related conditions. This underscores the need for further exploration into the effects of SSRIs.”

Looking ahead, Ayres and Gallant plan to investigate appropriate dosing regimens for fluoxetine in septic patients and are eager to see if other SSRIs yield similar benefits.

“Given that fluoxetine is among the most widely prescribed medications in the United States, it fosters a collaborative defense between host and pathogen to guard against infection-induced illnesses and fatalities,” remarks Ayres, who also leads the Molecular and Systems Physiology Laboratories at Salk. “Discovering its dual protective effects in a repurposed medication is truly exciting.”

Co-authors include Karina Sanchez, Emeline Joulia, and Christian Metallo from Salk, along with Jessica Snyder from the University of Washington.

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