- Design
- Adaptive randomised placebo-controlled trial
- Population
- 399 adults in Brazil with fatigue 3–24 months after confirmed 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 lasting from 90 days to two years after confirmed SARS-CoV-2 infection. Participants took fluvoxamine 100 mg twice daily, extended-release metformin, or placebo for 60 days.
On the Fatigue Severity Scale, which runs from 1 to 7 and started near 5.7, fluvoxamine lowered scores by 0.43 points more than placebo at day 60 and 0.58 at day 90, with a 99% posterior probability of superiority. Quality of life also improved. Adverse events were less common with fluvoxamine (24.0%) than placebo (35.5%). The metformin arm was cut in dose because of side effects and stopped for futility, so its result is inconclusive.
The effect is real but small, the follow-up is only 90 days, and fatigue was the only symptom studied. Fluvoxamine is a strong CYP1A2 inhibitor, so interactions need checking before anyone considers it.
- Consider fluvoxamine only as a discussion point for persistent long COVID fatigue, not a standard treatment
- Check for CYP1A2 interactions, including theophylline, clozapine, tizanidine and warfarin, before any SSRI of this kind
- Keep pacing advice and screening for depression, anaemia and thyroid disease as the first steps
- Tell patients the benefit seen was small and only measured to 90 days
Why it matters
Long COVID fatigue has almost no tested drug options, and this is one randomised signal among very few.
Don't overread it
A half-point change on a seven-point scale over 90 days is not evidence of lasting recovery.
The statistics, in plain English
This trial used Bayesian statistics, so it reports the probability that fluvoxamine is better than placebo (99%) rather than a p-value. That tells you the direction is very likely right; the size of the difference, about half a point, tells you how much it matters.
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