Psychiatric Drugs Could Be the Key to Treating Covid-19

7 min readDec 19, 2020

Photo illustration sources: Larry Washburn; Andriy Onufriyenko; Getty Images

Atthe beginning of the pandemic, doctors in France prepared for an influx of psychiatric patients with Covid-19, creating special units in hospitals to care for people with mental health problems who contracted the novel coronavirus. People with psychiatric disorders were presumed to be at an increased risk for infection because of potential difficulties complying with protective measures, limited access to health care, close living conditions for those residing in psychiatric wards, and high rates of comorbidities like diabetes and cardiovascular disease. But to the doctors’ surprise, the units remained largely empty, even during the most severe stage of the pandemic.

This observation led the doctors to ask whether psychiatric drugs could be offering some protection against the coronavirus. Sure enough, they found that 10 of the 18 most commonly prescribed psychiatric drugs — antidepressant, antipsychotic, and anti-anxiety medications — have known antiviral properties, including against the coronaviruses SARS and MERS.

Four different types of therapies — the antiviral drug remdesivir, convalescent plasma from recovered patients, monoclonal antibodies, and the steroid dexamethasone — are currently authorized by the U.S. Food and Drug Administration (FDA) to treat severe Covid-19. But three of these therapies are expensive and must be administered intravenously, while the fourth, dexamethasone, can actually backfire and suppress the immune system if given prematurely.

What is still desperately needed, physicians say, is a safe, cheap oral medication that could be prescribed to people with mild Covid-19 to ease their symptoms, help fight the infection early on, and prevent their decline into more severe disease. Ideally, this would be a drug that’s already approved for another purpose, which would speed up the authorization process and get the medication to patients as soon as possible. Some experts are now saying that psychiatric drugs could fit the bill.

“We don’t have anything that can be rolled out on a large scale for outpatients to prevent people from getting into hospital,” says Ilan Schwartz, MD, PhD, an infectious disease physician at the University of Alberta. “Having a therapy that’s already widely available, ideally it’s off-patent so it’s cheap, and for which there’s already a lot of safety data — something with those attributes that could be used against Covid-19 would really be fantastic.”

What is still desperately needed… is a safe, cheap oral medication that could be prescribed to people with mild Covid-19 to ease their symptoms, help fight the infection early on, and prevent their decline into more severe disease.

The antidepressant fluvoxamine may be exactly that. A recent study published in the Journal of the American Medical Association found that people who were given fluvoxamine within seven days of developing Covid-19 symptoms were less likely to have a drop in their oxygen levels and be hospitalized than people who received a placebo.

“For the fluvoxamine group, we had 80 individuals and none of them had clinical deterioration. But for the placebo group, which was 72 people, six of them deteriorated,” says Angela Reiersen, MD, an associate professor of psychiatry at Washington University who led the study. “That was a statistically significant difference, so it suggests that the fluvoxamine may be preventing the clinical deterioration in terms of a drop in the respiratory function.”

At first glance, it makes little sense that an antidepressant targeting chemicals in the brain would have any impact on a viral infection. Fluvoxamine is classified as a selective serotonin reuptake inhibitor (SSRI), which means it increases levels of serotonin in the brain and body. However, it turns out the drug also activates a protein called the sigma-1 receptor (sigmaR1) that is involved in many fundamental cellular processes — ones that the coronavirus hijacks in order to replicate and spread throughout the body.

There is now mounting evidence that manipulating sigmaR1 could have both antiviral and anti-inflammatory effects against Covid-19. “We didn’t [test fluvoxamine] because of it being an SSRI or an antidepressant,” Reiersen says. “The reason we looked at fluvoxamine was because of its sigma-1 receptor activity.”

Back in April, an international group of scientists screened for all of the places where SARS-CoV-2 proteins and human cellular proteins interacted. Then, in a follow-up study published in October, they tested whether getting rid of each of those human proteins affected the virus’s ability to infect and replicate in the cell. From the two studies, sigmaR1 emerged as a key location where the virus binds to and manipulates human cells and one that is crucial for the virus’s survival.

SigmaR1 is a complicated human protein involved in many fundamental cellular processes, such as energy regulation and the production and transport of other proteins. Scientists aren’t exactly sure why the virus is targeting it. It’s not where the virus enters the cells — that’s the now infamous ACE2 receptor. But once inside, it appears that the virus somehow uses sigmaR1 to turn the cell into a virus-producing factory.

“[SigmaR1 has] been linked to a lot of different pathways, and the question is, which one of those pathways is the one connected to viral infection? More work is needed to flesh that out,” says Nevan Krogan, PhD, a professor in the department of cellular and molecular pharmacology at the University of California San Francisco who led the research. “A viral protein will spend more of its time trying to hijack proteins that are involved in many different pathways and processes so they get a bigger bang for the buck. In that regard, I think it is probably a smart move for the virus to attack this receptor. But the exact details of why the manipulation is beneficial, we don’t know.”

“We didn’t [test fluvoxamine] because of it being an SSRI or an antidepressant. The reason we looked at fluvoxamine was because of its sigma-1 receptor activity.”

Krogan’s team next looked for existing drugs that act on sigmaR1 and tested whether those medications interfere with the coronavirus’s ability to infect human cells in a dish. They identified several psychiatric drugs, including the same antidepressant used in the clinical trial, fluvoxamine, as well as some antipsychotic medications, that had antiviral properties against SARS-CoV-2, presumably because of their effect on sigmaR1.

In a final step, the researchers retrospectively analyzed data from people who were hospitalized for Covid-19 and had also been given an antipsychotic. The people who had taken an antipsychotic that acted on sigmaR1 (a class of drugs called “typical” antipsychotics) were significantly less likely to be ventilated than people who received an “atypical” antipsychotic that did not affect the protein.

“We’re not saying people [with Covid-19] should be on antipsychotics. This was, in my mind, more of a proof of principle,” Krogan says. “But, in my opinion, sigmaR1 is important for infection without a doubt — we’ve genetically shown that — and known sigmaR1 modulators have antiviral effects.”

Afew prior studies have looked at the role of sigmaR1 in viral infections. For instance, research from 2013 showed that the protein is important for infection with the hepatitis C virus, and decreasing levels of the protein interfered with the virus’s ability to infect cells.

“At this point in the pandemic, I think we need to be very skeptical about embracing therapies without much more robust data.”

Reiersen, the Washington University psychiatrist, was tipped off to the protein’s role in another aspect of infections — inflammation. A 2019 study showed that mice lacking sigmaR1 were more likely to die from hyper-inflammation, while mice given fluvoxamine to activate the protein were more likely to survive. When news emerged in March that people with Covid-19 were dying because of the hyper-inflammatory cytokine storms, Reiersen launched a clinical trial to see if the drug might be helpful. “I thought maybe we could use fluvoxamine to try to prevent the clinical deterioration that might be related to the inflammation,” she says.

Schwartz, the infectious disease physician, says that the initial clinical trial data for fluvoxamine are promising and that he expects a larger phase 3 study will follow. “I’m quite encouraged by the fact that there are some quite serious scientists that have looked at the data quite carefully and decided that there is merit going forward,” he says. But, he adds, “at this point in the pandemic, I think we need to be very skeptical about embracing therapies without much more robust data.”

WRITTEN BY

Dana G Smith

Senior writer for Elemental @ Medium • PhD in 🧠 • dsmith@medium.com @smithdanag

1K

7

Sign up for Inside Your Head 🧠

By Elemental

A weekly newsletter exploring why your brain makes you think, feel, and act the way you do, by Elemental senior writer Dana Smith. Take a look

Get this newsletter

By signing up, you will create a Medium account if you don’t already have one. Review our Privacy Policy for more information about our privacy practices.