- Design
- Randomised, placebo-controlled, adaptive Bayesian trial
- Population
- 399 adults in Brazil with fatigue 3 to 24 months after COVID-19
- Primary outcome
- Change in Fatigue Severity Scale score
- Effect
- Fluvoxamine vs placebo −0.43 at day 60, −0.58 at day 90; posterior probability of superiority 99%
An adaptive, placebo-controlled trial at outpatient sites in Brazil randomised 399 adults with fatigue 3 to 24 months after confirmed SARS-CoV-2 infection to fluvoxamine 100 mg twice daily, extended-release metformin, or placebo for 60 days.
On the Fatigue Severity Scale (baseline about 5.6 to 5.9 on a 1 to 7 scale), fluvoxamine lowered scores by 0.43 points versus placebo at day 60 and 0.58 at day 90, with a 99% Bayesian probability of superiority. Quality of life also improved. Adverse events were less frequent with fluvoxamine than placebo. The metformin arm had its dose cut for side effects and was stopped for futility, leaving its result inconclusive.
Long COVID fatigue has almost no tested drug options, so a randomised signal matters. But the effect is modest, the follow-up is short, and the trial looked only at fatigue.
Fluvoxamine strongly inhibits CYP1A2 and CYP2C19, so interactions, notably with clozapine, theophylline, tizanidine and some anticoagulants, need checking before any use.
- Fluvoxamine is a reasonable option to discuss for persistent long COVID fatigue, with modest expected benefit
- Check for interactions before prescribing: fluvoxamine strongly inhibits CYP1A2 and CYP2C19
- Do not use metformin for long COVID fatigue on this evidence
- Keep pacing and graded return to activity as the foundation of fatigue management
Why it matters
It is one of very few randomised trials to show any drug easing long COVID fatigue.
Don't overread it
Benefit beyond 90 days and effects on other long COVID symptoms were not tested.
The statistics, in plain English
A 0.58-point drop on a 7-point fatigue scale is modest; it is not clear how many patients would notice it. A 99% posterior probability of superiority means the benefit is very likely real, not that it is large.
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