Can Antidepressants Fight Deadly Infections? Study Says Yes!

Antidepressants like Prozac are widely used to treat mental health conditions, but recent research suggests they may have another surprising benefit—helping the body fight infections and prevent life-threatening sepsis. Scientists at the Salk Institute have discovered how these medications regulate the immune system, potentially leading to new treatments that could save lives and improve global preparedness for future pandemics.

This study builds on previous findings that people taking selective serotonin reuptake inhibitors (SSRIs), such as Prozac (fluoxetine), experienced milder COVID-19 symptoms and were less likely to develop long COVID. Now, researchers are uncovering how these drugs protect the body from severe infections.

Prozac’s Unexpected Role in Infection Defence

A recent study found that fluoxetine helped protect mice from sepsis, a dangerous condition in which the immune system overreacts to an infection, leading to organ failure and even death. Researchers at the Salk Institute identified the biological process behind this defence, bringing fluoxetine closer to clinical trials for treating infections and immune-related disorders.

"When fighting an infection, the ideal treatment should kill the harmful bacteria or virus while also protecting our tissues and organs," said Professor Janelle Ayres, a lead researcher at Salk. "Most medications focus only on eliminating pathogens, but fluoxetine does both. This is incredibly exciting, especially since it's a drug we already know is safe for humans."

The human immune system is designed to protect against infections, but sometimes it overreacts, causing serious damage. This overreaction is seen in conditions like sepsis and severe COVID-19, where inflammation gets out of control and harms healthy tissues.

Suppressing the immune response might seem like a solution, but it can make patients more vulnerable to infections. The best treatment would instead:

1. Control the immune response to prevent damage

2. Kill harmful bacteria or viruses before they spread

Fluoxetine appears to do both, making it a promising candidate for infection treatment.

How Fluoxetine Protects Against Infections

To understand fluoxetine’s effects, researchers studied two groups of mice infected with bacteria. One group was pre-treated with fluoxetine, while the other was not. The results were striking—mice given fluoxetine were protected from sepsis, organ damage, and death.

Scientists then conducted follow-up experiments to understand why. Here’s what they found:

- Fluoxetine slows bacterial growth – Mice given the drug had fewer bacteria in their system just eight hours after infection, suggesting that fluoxetine has natural antimicrobial properties.

- Fluoxetine reduces harmful inflammation – The drug boosted IL-10, an anti-inflammatory molecule that helped prevent dangerous blood fat imbalances (hypertriglyceridemia) linked to sepsis. This protected the heart and other organs from damage.

- Fluoxetine offers two levels of protection – First, it directly fights bacteria. Second, it prevents the body from harming itself through excessive inflammation.

These findings suggest that fluoxetine and possibly other SSRIs could help treat infections and reduce immune system damage.

Not Just About Serotonin

To test if fluoxetine’s immune benefits were linked to serotonin, the brain chemical it typically affects, researchers conducted another experiment. They studied two new groups of fluoxetine-treated mice—one with normal serotonin levels and one without.

Surprisingly, fluoxetine’s infection-fighting abilities had nothing to do with serotonin. Regardless of serotonin levels, the drug still:

- Protected against infections

- Prevented organ damage

- Lowered inflammation

This suggests that SSRIs do more than regulate mood—they also impact immune function.

"That was really unexpected," said Robert Gallant, the study’s first author. "Knowing that fluoxetine can help regulate the immune system, fight infections, and reduce damage—without relying on serotonin—opens new doors for treating life-threatening illnesses."

What’s Next? Potential for New Infection Treatments

The research team plans to explore how fluoxetine dosing could be optimized for treating sepsis and other infections. They also want to see if other SSRIs offer similar benefits.

"Fluoxetine is one of the most commonly prescribed drugs in the U.S.," said Professor Ayres. "The fact that it can protect against infection-related illness and death makes it an exciting candidate for repurposing as a dual-purpose medication."

If further studies confirm these findings, fluoxetine and other SSRIs could become key players in fighting serious infections, potentially reducing hospitalizations and saving lives worldwide.

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