- Design
- Randomised, placebo-controlled, adaptive Bayesian trial
- Population
- 399 outpatients in Brazil with fatigue 3 to 24 months after confirmed SARS-CoV-2 infection
- Primary outcome
- Change in Fatigue Severity Scale score
- Effect
- Fluvoxamine vs placebo −0.43 at day 60 and −0.58 at day 90; posterior probability of superiority 99%
This Brazilian outpatient trial randomised adults with persistent fatigue after COVID-19 to fluvoxamine 100 mg twice daily, extended-release metformin, or placebo for 60 days, following them to day 90.
Fluvoxamine improved fatigue and quality-of-life scores compared with placebo, with a high probability that the effect was real. The size was modest. Metformin was stopped for futility after side effects forced a dose reduction.
For the general physician, fluvoxamine is an inexpensive and familiar drug, but its interaction profile is the practical barrier, particularly in multimorbid patients on several medicines.
- Fatigue Severity Scale scores fell about 0.4 to 0.6 points more than placebo.
- Adverse events were less frequent with fluvoxamine than with placebo or metformin.
- Fluvoxamine strongly inhibits CYP1A2 and CYP2C19; check clozapine, theophylline, warfarin and clopidogrel.
- Metformin results were inconclusive after a dose cut for side effects.
- Rule out anaemia, thyroid disease, depression and sleep disorders before attributing fatigue to long COVID.
Why it matters
Long COVID fatigue has had no drug with randomised support; this is a first signal, not yet an established treatment.
Don't overread it
The effect was about half a point on a seven-point scale, and benefit beyond 90 days is unknown.
The statistics, in plain English
The trial reports a Bayesian probability: 99% that fluvoxamine is better than placebo. That says the effect is likely real, not that it is large; half a point on the fatigue scale may or may not feel meaningful to a patient.
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