- Design
- Randomised, placebo-controlled, adaptive (Bayesian) trial
- Population
- 399 adults with fatigue 90 days to 24 months after confirmed COVID-19, Brazil
- 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%)
An adaptive, placebo-controlled trial at outpatient sites in Brazil randomised 399 adults with fatigue between three months and two years after confirmed SARS-CoV-2 infection to fluvoxamine 100 mg twice daily, extended-release metformin, or placebo for 60 days.
On the 1-to-7 Fatigue Severity Scale, fluvoxamine improved scores against placebo 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 frequent with fluvoxamine than placebo. The metformin arm was cut in dose because of side effects and then stopped for futility.
The effect is modest, the follow-up short, and the trial looked only at fatigue. It is one of few positive randomised results in long COVID, but it needs replication before it becomes routine treatment.
- Long COVID fatigue now has one small positive trial of fluvoxamine; discuss it as an option under evaluation.
- Check for interactions before considering fluvoxamine — it strongly inhibits CYP1A2, raising levels of drugs such as theophylline and clozapine.
- Do not prescribe metformin for long COVID fatigue on this evidence.
- Keep screening for depression, sleep disorders and anaemia, which also cause fatigue.
Why it matters
Clinicians seeing persistent post-COVID fatigue have had almost nothing with randomised support to offer.
Don't overread it
One trial with 90-day follow-up and a modest effect on one symptom is not established treatment.
The statistics, in plain English
A posterior probability of 99% is a Bayesian statement that, given the data and the model, fluvoxamine is very likely better than placebo. It says nothing about how much better; here the gain was about half a point on a seven-point scale.
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