While usage varies significantly by country, millions of people around the world use psychotropic medications, particularly depression treatments like selective serotonin reuptake inhibitors (SSRIs) such as Prozac. Scientists have found that SSRI users who had COVID-19 had less severe infections and were less likely to develop long COVID compared to those not using SSRIs. These antidepressants could help protect people from serious infections and sepsis, in which an infection sparks a major and uncontrolled immune response with life-threatening complications. Now scientists have learned more about how SSRIs interact with the immune system and aid in the defense against infection. The findings have been reported in Science Advances.
Previous work has shown that fluoxetine, sold as Prozac, can protect mice from sepsis. In this situation, the immune response spirals out of control, and causes damage to tissues, organ failure, and may lead to death. But immune suppression does not always help sepsis patients, who are also fighting their initial infection, and need the help of their immune system.
In this study, the researchers analyzed a mouse model of bacterial infection. The mice were put into groups, one of which had been given fluoxetine prior to their infection while the other group was untreated. The fluoxetine-treated mice were shown to have protection from sepsis and organ damage, and did not die, unlike mice in the other group.
The researchers determined that the mice on SSRIs carried lower levels of bacterial pathogens compared to untreated mice, eight hours after the start of their infection. So they had a less severe infection to begin with; and the researchers suggested that fluoxetine has some antibacterial effects that limit microbial growth.
The SSRI-treated mice also had higher levels of the antinflammatory signal IL-10. This could indicate that IL-10 is preventing a disorder known as sepsis-induced hypertriglyceridemia, or abnormally high blood triglyceride levels. Since this did not occur in treated mice, they were protected from mortality.
“When treating an infection, the optimal treatment strategy would be one that kills the bacteria or virus while also protecting our tissues and organs,” said Professor Janelle Ayres, holder of the Salk Institute Legacy Chair and a 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.”
These effects also appear to be totally unrelated to circulating serotonin; mice with or without circulating serotonin displayed the same positive reaction to an infection after SSRI treatment.
Sources: Salk Institute, Science Advances