SSRI antidepressants may be effective early treatments for COVID-19

Researchers at Washington University School of Medicine in St. Louis published the results of a clinical trial evaluating an antidepressant, fluvoxamine, for early treatment for COVID-19. The study was published in JAMA, The Journal of the American Medical Association, and was funded by the COVID-19 Early Treatment Fund (CETF).

Fluvoxamine, which is a generic, but sometimes sold under the brand name Luvox, is a member of the class of drugs known as selective serotonin reuptake inhibitors (SSRIs). Other drugs in this class include Prozac (fluoxetine), Zoloft (sertraline), and Paxil (paroxetine). Fluvoxamine is used to treat social anxiety disorder or obsessive-compulsive disorder.

The study investigated whether taking fluvoxamine within seven days of the first symptoms of COVID-19 can reduce the risk of respiratory deterioration. The study showed that the drug was effective: none of the 80 patients receiving the drug met the criteria for respiratory deterioration compared to the 8.3% rate in the 72 patients in the placebo cohort.

“The results of the fluvoxamine study are encouraging and warrant further evaluation in a larger study,” said Carolyn Machamer, professor of cell biology at Johns Hopkins School of Medicine and a member of the CETF Scientific Advisory Committee. “Treatment that can prevent lung problems in people with mild symptoms of COVID-19 is desperately needed.”

They chose to investigate fluvoxamine because it has strong anti-inflammatory activity. The research team, led by Eric Lenze, director of the Healthy Mind Lab at Washington University School of Medicine in St. Louis, thought the anti-inflammatory properties could prevent cytokine storms, the massive overactive immune response seen in severe cases of COVID. -19.

“This placebo-controlled study indicates that fluvoxamine can prevent severe breathing problems in people with mild COVID-19 disease, and is the first in this patient population to be published in a peer-reviewed journal,” Lenze said. “There are promising results and we look forward to conducting a much larger study in the coming weeks to further evaluate the efficacy of fluvoxamine.”

All 152 study participants were 18 or older and had been diagnosed with mild COVID-19. They all lived in Missouri or Illinois. They were randomized 1: 1 to receive fluvoxamine or placebo. There was no face-to-face contact between the participants and the doctors – all the test material, including the drug, was delivered to the patients’ homes.

Of the 80 participants who received fluvoxamine, none met the clinical deterioration endpoint, which was defined as oxygen saturation of 92% or less along with difficulty breathing or hospitalization for pneumonia. Of the 72 people who received the placebo, six experienced respiratory deterioration.

“We now have evidence that an inexpensive, safe and readily available pill can reduce deterioration and hospitalization from COVID-19,” said Steve Kirsch, founder of CETF. “This study validates what we have already learned from more scientific studies, the greater the activation of sigma-1, the greater the protection.”

Coronavirus replication occurs in a modified membranous compartment derived from the endoplasmic reticulum (ER). The sigma-1 receptor is bound to the ER membrane and acts as an upstream modulator of ER stress. Therefore, the researchers suspected that sigma-1-activating drugs could be used to treat COVID-19.

The study authors note that it is limited by the small sample size and short follow-up duration. To actually determine whether fluvoxamine is effective will require larger randomized trials with “more definitive outcome measures”.

The study confirms a large multi-center observation study conducted in France that showed that SSRI drugs significantly reduced the risk of COVID-19 patients requiring a ventilator or dying from COVID-19. The French study suggested that SSRIs with the highest sigma-1 receptor activation had the greatest benefits.