SSRI Antidepressants May Be Effective Early Treatments for COVID-19

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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 disorders.

The trial evaluated whether taking fluvoxamine within seven days of first symptoms of COVID-19 can decrease the risk of respiratory deteriorating. The study showed the drug was effective—none of the 80 patients receiving the drug hit the respiratory deteriorating criteria compared to the 8.3% rate in the 72 patients in the placebo cohort.

“The results of the fluvoxamine trial are encouraging and warrant a further evaluation in a larger study,” said Carolyn Machamer, professor of cell biology at the Johns Hopkins School of Medicine and a member of CETF’s scientific advisory board. “A 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 might prevent cytokine storms, the massive overactive immune response seen in severe cases of COVID-19.

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

All of the 152 trial participants were 18 years or older and had been diagnosed with mild COVID-19. They all lived in either Missouri or Illinois. They were randomized 1:1 to receive either fluvoxamine or placebo. There was no face-to-face contact between participants and clinicians—all trial materials, including the drug, were delivered to the patients’ homes.

Of the 80 participants who received fluvoxamine, none hit the endpoint of clinical deterioration, which was defined as oxygen saturation of 92% or lower 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 trial validates what we have already learned from multiple scientific studies, the greater the sigma-1 activation, 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. As such, researchers have suspected that drugs that activate sigma-1 might be used to treat COVID-19.

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

The study does confirm a large, multi-center observation study conducted in France that demonstrated that SSRI drugs significant decreased the risk of COVID-19 patients requiring a ventilator or dying from COVID-19. The French study suggested the SSRIs with the highest sigma-1 receptor activation had the most benefit.

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