An antidepressant called fluvoxamine reduces fatigue in people with long COVID, at least in the short term, according to a new study that tested the drug against a placebo.

In a randomized clinical trial of 399 people, all participants had significant fatigue, measured by a score of at least four points on aseven-point scale called the Fatigue Severity Scale, a validated measure in which people rate their level of tiredness or exhaustion. Seven points on the scale indicates the worst fatigue. 

After 30 days on medication, people randomly assigned to take fluvoxamine were nearly 50% more likely than those assigned to take a placebo to rate their fatigue as three or less. After 60 days, fluvoxamine lowered participants’ self-reported fatigue ratings by nearly half a point, according to the study, published today in Annals of Internal Medicine. Those taking fluvoxamine also reported better quality of life and fewer adverse events than those taking a placebo.

The new study also tested metformin, a diabetes drug that can help prevent long COVID. Researchers found that metformin didn’t alleviate fatigue more than a placebo. 

But the results suggest that fluvoxamine is worth trying in people with long COVID, study co-author Jamie Forrest, PhD, MPH, scientific director of the University of British Columbia’s Health Equity & Resilience Observatory in Vancouver, Canada, told CIDRAP News.

Forrest said his goal is to “get people back to feeling normal.” In that regard, “I think fluvoxamine’s done great.”

Although people with long COVID can experience a wide variety of symptoms, fatigue is the most common. Many people with long COVID feel so exhausted that they can no longer work or take care of their family. Other problems experienced by people with long COVID include joint and muscle pain, heart palpitations, memory problems (commonly called brain fog), sleep disturbances, headaches, digestive problems, and new autoimmune diseases.

Forrest said he wants to study potential treatments for pain and other long-COVID symptoms.

“We now have one drug that’s effective,” Forrest said. “It’s time to find the next drug, and the next drug after that.”

Repurposing an old drug

Long-COVID researchers have focused on fluvoxamine because it also reduces inflammation and lowers the risk of hospitalization in people with acute COVID-19 infections, Forrest said.

Available as a generic or under the brand name Luvox, fluvoxamine is typically prescribed for obsessive-compulsive disorder. Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI), which works by changing the activity of serotonin, a chemical that affects mood and other functions. 

It’s time to find the next drug, and the next drug after that.

The clinical trial was conducted in 22 outpatient medical facilities in Brazil from October 2023 to February 2025. Participants included adults with a single episode of COVID-19 and new or worsening fatigue lasting at least 90 days and no more than one year. Study participants, who weren’t told which medication they were receiving, took two pills a day for 60 days. The study excluded people already taking the study drugs and those with substance use disorder or uncontrolled psychiatric conditions. 

Because the study was conducted in Brazil, it’s possible that people living in other places might not have the same results, the authors wrote in the study.

Length of benefit not yet known

In the clinical trial, fluvoxamine’s benefits declined over time.

After 60 days on medication, those taking fluvoxamine were 36% more likely to rate their fatigue as less than three on the seven-point scale. At 90 days—30 days after participants stopped taking medication—those assigned to fluvoxamine were only 19% more likely to rate their fatigue as less than three.

Jenn Brenon, who has lived with severe long-COVID symptoms since 2020, said she wonders if fluvoxamine provides only short-term relief. 

“It is encouraging, but it’s too early to tell if it’s a long-term or short-term cure or symptom relief,” said Brenon, 42, who lives in Brooklyn, New York.

Forrest said it’s possible that the relative benefits of fluvoxamine declined as some people taking a placebo recovered on their own. 

Some patients recover, many improve partially, but durable full remission is far from guaranteed, especially once long COVID is established, said Alba Azola, MD, an assistant professor in physical medicine and rehabilitation at Johns Hopkins University School of Medicine who oversees long COVID clinics and was not involved in the new research.

A large study called Researching COVID to Enhance Recovery (RECOVER), run by the National Institutes of Health (NIH), found that fewer than 20% of people with long COVIDappeared to recover.

One condition, many symptoms

For Brenon, long COVID caused far more problems than just fatigue.

Brenon also has suffered from spikes in her blood pressure, migraine headaches, gastrointestinal problems, scarring in her lungs, and a phlegmy cough, similar to bronchitis. The cough afflicted her daily for about a year and a half. Even today, the cough returns during hot, humid weather or when she takes a hot shower. 

Brenon said she can take only cool showers today. She cranks up the air conditioning when the temperatures begin to climb.

“I can’t breathe when it’s hot and humid,” the former preschool teacher said. “I have two masters degrees, for teaching and administration, but I can’t do either one.”

Although results of magnetic resonance imaging scans were normal for the first few years of her illness, recent brain scans suggest that Brenon has been having seizures, although she doesn’t recall experiencing any.

For Brenon, long COVID “gets worse every year,” she said. “If I fix one thing, another thing goes wrong.”

Without an effective cure for long COVID, doctors typically treat symptoms as they appear. For example, Brenon said she takes anti-seizure medication, as well an antidepressant called Wellbutrin and monthly infusions of intravenous immunoglobulin, a therapeutic treatment made from donated blood plasma containing concentrated antibodies, which can boost immune function or reduce inflammation. The infusions, given over five days, “give me two or three good weeks” at a stretch, Brenon said.

Limited enthusiasm for fluvoxamine

Azola said she hasn’t seen much benefit from fluvoxamine in her patients.

“I don’t want to be pessimistic, but that particular intervention is not something that is getting me excited,” Azola said. “Overall, the findings suggest a potential modest benefit.”

People need to be careful how they interpret the study’s results, Azola said. Researchers also need to do “further work” to clarify how improvements in fatigue on a seven-point scale mean for patients in their everyday lives.

Overall, the findings suggest a potential modest benefit.

Researchers have studied SSRIs in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition also marked by exhaustion and other symptoms, since the 1990s without much success, Azola said. Many researchers consider long COVID to be a form of ME/CFS. Testing SSRIs against long COVID feels like trying to “reinvent the wheel,” Azola said.

“One of the things that has held back long-COVID research is not learning about what’s been done and building from that knowledge learned decades ago,” she said.