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A drug’s established use does not capture all the biological systems it affects.

Fluvoxamine modestly reduced persistent fatigue in adults with long COVID.

Prucalopride improved several cognitive measures after depression had remitted.

Some of the most disabling symptoms of an illness can also be among the hardest to measure and treat.

A person may no longer meet the criteria for major depression yet still struggle to concentrate, remember information, or think quickly. Someone with long COVID may appear physically recovered while experiencing exhaustion so severe that ordinary work, exercise, or household tasks become overwhelming.

These symptoms are sometimes minimized because they are subjective, invisible, or difficult to capture with standard medical tests. Two recent clinical studies, however, suggest that medications originally developed for very different purposes may help address persistent fatigue and cognitive dysfunction.

One trial found that fluvoxamine, an antidepressant, modestly reduced fatigue in adults with long COVID. Another found that prucalopride, a medication approved for chronic constipation, improved performance on several cognitive tests in people whose depression was in remission.

Neither medication is a proven cure for these conditions. But together, the studies illustrate two important ideas: Recovery is not always complete when the most obvious symptoms improve, and existing medications may have useful effects beyond the conditions named on their labels.

An Antidepressant for Long COVID Fatigue

The REVIVE-TOGETHER trial included 399 adults in Brazil who had experienced persistent fatigue for at least 90 days after a confirmed COVID-19 infection. Participants received fluvoxamine, metformin, or a placebo for 60 days.

Fluvoxamine performed better than placebo in reducing fatigue, with benefits still evident at the 90-day follow-up. Participants also reported improvement on several quality-of-life measures. Metformin, despite previous evidence that it may reduce the risk of developing long COVID when taken during acute infection,........

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