Small Study Suggests Antidepressant Fluvoxamine Could Treat COVID-19

An antidepressant already on the market could pave the way toward more affordable and accessible treatment for people with a symptomatic COVID-19 infection. A new clinical trial using the psychiatric drug fluvoxamine (brand name Luvox) showed promise in a Washington University trial in reducing serious outcomes for people with the virus. Researchers compared the course of illness for those who took the drug compared to a placebo group.

According to the study, there was no “clinical deterioration” out of 80 participants in the trial who took fluvoxamine compared to six out of 72 in the placebo group. Scientists said the difference of 8.3% between the two groups is clinically significant. For the purposes of the study, clinical deterioration was defined as “(1) shortness of breath or hospitalization for shortness of breath or pneumonia and (2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.”

Although this trial focused on the outcomes of patients who took fluvoxamine, lead researcher Eric Lenze, M.D., said it could open the door to looking at how other mental health drugs could impact the course of COVID-19. “We think it would be very interesting if other drugs are effective as well — other antidepressants,” said Dr. Lenze. And there may be good reasons to explore this possibility.

Previous studies have looked at the effects of antidepressants on the immune system and their anti-inflammatory properties. Researchers explained that selective serotonin reuptake inhibitors (SSRIs) used to treat depression can increase and change the activity of immune cells. In one study, scientists found that serotonin was passed easily between immune cells. A finding, they said, could restore healthy immune function for people with depression.

But in the case of fluvoxamine, something sets it apart from other antidepressants — giving it the leading role in this research. Lenze explained scientists in this trial picked fluvoxamine because of its ability to bind easily with the sigma-1 receptor, increasing the potential for regulating inflammation. “Among anti-depressants it’s by far the most potently binding to and activating this receptor.” The sigma-1 receptor is a chaperone protein that has been shown to have the strongest tie to the immune system.

An earlier study in October 2020 explored the connection between the sigma-1 receptor protein and COVID-19, identifying that drugs that interact with the receptor were effective at reducing the chances someone would end up on a ventilator.  The October study also identified interactions between COVID-19 and the protein PGES-2, which is targeted by the anti-inflammatory drug indomethacin.

Dr. Francis Collins with the National Institute of Health explained that “these findings provide a remarkable demonstration of how basic molecular and structural biological findings can be combined with clinical data to yield valuable new clues for treating COVID-19 and other viral illnesses, perhaps by repurposing existing drugs.”

Looking more closely at sigma-1 receptor, its ability to diminish the effects of the virus may have to do with the way COVID-19 attacks the body’s cells. To get technical, researcher José Miguel Vela explained how coronaviruses replicate in a membranous compartment of the endoplasmic reticulum — prompting stress and facilitating the host cell’s vulnerability to the virus’ needs. That’s where the protein comes in.

“Sig-1R regulates key mechanisms of the adaptive host cell stress response and takes part in early steps of viral replication,” Vela wrote, adding:

Targeting Sig-1R is not expected to reduce dramatically established viral replication, but it might interfere with early steps of virus-induced host cell reprogramming, aid to slow down the course of infection, prevent the aggravation of the disease and/or allow a time window to mature a protective immune response.

Lenze’s fluvoxamine trial seems to provide early evidence that proves this theory. So what’s next? Researchers from Washington University are already recruiting more patients for a second, larger clinical trial testing the abilities of fluvoxamine to keep COVID-19 patients from getting very sick.

An added benefit of this drug is that it’s already widely available and could be an affordable option for patients early in the course of the disease if results are confirmed. “Doctors could immediately prescribe it what’s called off-label for the early treatment of COVID,” said Lenze.

But for researchers, finding participants for trials has been a hurdle to discovering adequate therapies for COVID-19 patients. “The reason we don’t have more treatments is that we haven’t had many successful clinical trials,” Lenze said.

“If we confirm this finding in a larger study it would suggest that maybe particularly for people at high risk for developing serious COVID they could take [fluvoxamine] to prevent that from happening — stay out of the hospital, stay off a ventilator.”

If you’re interested in participating in the next trial, you can visit the trial’s recruitment website here and check if you’re eligible. Lenze and his team are particularly looking for people who have current and recent COVID-19 symptoms. The trial is contact-free, can be done from your home — you will be asked to take fluvoxamine or a placebo while reporting your symptoms.