- Design
- Randomised, placebo-controlled, adaptive trial
- Population
- 399 adults in Brazil with fatigue 90 days to 24 months after confirmed SARS-CoV-2 infection
- Primary outcome
- Change in Fatigue Severity Scale score
- Effect
- Mean difference −0.43 at day 60 and −0.58 at day 90 vs placebo; posterior probability of superiority 99%
This placebo-controlled adaptive trial, run at outpatient sites in Brazil, enrolled 399 adults with fatigue between 90 days and 24 months after confirmed SARS-CoV-2 infection. Participants took fluvoxamine 100 mg twice daily, extended-release metformin, or placebo for 60 days, with follow-up to day 90.
Fatigue Severity Scale scores started around 5.6 to 5.9 on a 7-point scale. Against placebo, fluvoxamine lowered the score by 0.43 points at day 60 and 0.58 at day 90, each with a 99% posterior probability of superiority, and quality of life also improved. Adverse events were less common on fluvoxamine (24%) than on placebo (35.5%). The metformin arm had its dose cut for side effects and was then stopped for futility, so its result is inconclusive.
For patients with persistent fatigue after COVID-19, options have been limited to pacing and rehabilitation. This is a modest but consistent effect from a randomised trial, with good tolerability. It is reasonable to discuss fluvoxamine as a time-limited trial, keeping in mind that durability beyond 90 days is unknown and that fluvoxamine strongly inhibits CYP1A2.
- Consider discussing a 60-day trial of fluvoxamine with adults who have persistent fatigue after COVID-19.
- Check for interacting drugs first: fluvoxamine raises levels of clozapine, theophylline, tizanidine and others metabolised by CYP1A2.
- Set a review at about 8 to 12 weeks using a fatigue score to judge benefit.
- Keep pacing and graded activity advice in place alongside any drug.
Why it matters
Long COVID fatigue has had very few drug options with randomised evidence behind them.
Don't overread it
One trial, one country and a 90-day horizon; this is not yet a guideline recommendation.
The statistics, in plain English
A posterior probability of superiority of 99% is a Bayesian statement: given the data, there is a 99% chance fluvoxamine is better than placebo. It says nothing about how much better; the difference of about half a point on a 7-point scale is modest, and whether it feels meaningful to patients varies.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for internal medicine, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free