A widely available antidepressant drug may provide meaningful relief for people experiencing persistent fatigue from long-term COVID-19 infections, according to a global clinical trial co-led by McMaster University.
Researchers have found that fluvoxamine (sold under the brand name Luvox), an inexpensive drug already commonly used to treat depression and other symptoms, reduces fatigue and improves quality of life in adults with long-term COVID-19 infections. This randomized, placebo-controlled trial Annual report of internal medicine.
Possible treatment for long-term coronavirus fatigue
Fatigue is one of the most frequent and disabling symptoms reported by people with long-term COVID-19 infection. For some people, fatigue is severe enough to interfere with work, family responsibilities, and daily life. Despite the scale of the problem, there are still few treatments supported by strong clinical evidence.
“This is an important step forward for patients who have been craving evidence-based options,” says Edward Mills, senior author and professor in the School of Health Research Methods, Evidence and Impact at McMaster University and co-principal investigator on the trial. “Fluvoxamine has consistently shown meaningful benefits and is already widely used and well understood, so it has clear potential for clinical use.”
Researchers from Canada, Brazil and the United States jointly led the study. Clinical sites were located throughout the Brazilian states of Belo Horizonte and Minas Gerais.
The REVIVE-TOGETHER trial brought together researchers from McMaster University, the University of British Columbia, Stanford University, the University of Pittsburgh, Duke University, Georgetown University, and several institutions in Brazil.
Fluvoxamine and metformin testing
The study included 399 Brazilian adults who had persistent fatigue for at least 90 days after a confirmed SARS-CoV-2 infection. Participants were randomly divided into one of three groups and received fluvoxamine (sold under the brand name Luvox), metformin (a common diabetes drug), or a placebo for 60 days.
“We wanted to test whether two existing, widely available and affordable drugs were effective. We had biological reasons to think that both could be effective against long-term COVID-19 fatigue, but neither had been rigorously tested for this purpose in proper clinical trials,” Mills says.
Fluvoxamine performed better than placebo in reducing fatigue. Statistical analysis showed that the drug was more effective than a placebo 99% of the time. Participants who received fluvoxamine also reported improved overall quality of life across several measures.
The same results were not obtained with metformin. An early study found that taking metformin during the early stages of a coronavirus infection may reduce the risk of developing a long-term infection with the coronavirus. However, in this trial, the drug did not produce meaningful improvement in people who were already experiencing long-term coronavirus fatigue.
Adaptive clinical trial design
The researchers used a Bayesian adaptive trial design, which allowed them to terminate individual treatment groups early when the evidence was clear enough. This approach can draw reliable conclusions more quickly than traditional testing while maintaining scientific rigor.
“This trial had a sophisticated adaptive design that allowed us to reach our conclusions more efficiently than traditional trials and stop them earlier when the evidence was clear enough. This was a design innovation as important as the results themselves,” said lead author Gilmar Reis, a researcher at Card Research, a Brazilian clinical research center based in Belo Horizonte. Reis is also an adjunct associate professor at McMaster University.
Further research is still needed
The long-lasting coronavirus continues to pose a major global health challenge, with an estimated 65 million people affected worldwide. As proven treatments remain lacking, most medical recommendations focus on supportive strategies such as activity pacing and individual symptom management.
Researchers warn that fluvoxamine is not a complete solution to the long-lasting coronavirus. This condition can involve a variety of symptoms and biological processes, and this drug appears to be particularly promising for fatigue management.
Additional research will be needed to determine which patients are most likely to benefit, understand why the drug is effective, and explore whether it can be used in conjunction with other treatments in development.
“This trial gives clinicians the first strong evidence of a drug to alleviate long-term COVID-19 fatigue,” said Jamie Forrest, corresponding author and postdoctoral fellow at the University of British Columbia. “Patients want something they can try today, and this discovery brings us closer to that reality.”
This study was funded by the Ratna Foundation.
