Ann Intern Med

Common antidepressant reduces fatigue in long COVID patients

March 31, 2026

Clinical takeaway: Consider fluvoxamine as an evidence-based option for long COVID fatigue, particularly in patients with persistent symptoms ≥3 months; metformin doesn't appear effective for treatment.

In a randomized, placebo-controlled trial of 399 adults with long COVID, fluvoxamine (100 mg twice daily) significantly reduced fatigue scores at 60 days with sustained benefit at 90 days, compared with placebo and metformin arms. Fluvoxamine also improved quality of life across multiple time points, while metformin showed no meaningful benefit for fatigue. Adverse events were less frequent with fluvoxamine (20%) vs. placebo (~30%), and serious adverse events were rare.

Current care for long COVID remains largely supportive, making this one of the first randomized trials showing a medication benefit for fatigue.

“This is an important step forward," said Edward Mills, senior author and professor in McMaster University’s Department of Health Research Methods, Evidence, and Impact. "Fluvoxamine showed consistent and meaningful benefits.”

Source:

Reis G, et al. (2026, March 31). Ann Intern Med. The effect of fluvoxamine and metformin for fatigue in patients with long COVID: An adaptive randomized trial. https://pubmed.ncbi.nlm.nih.gov/41911553/