Rodríguez-Freire 2026 (INNOVA): a year of low-dose naltrexone for fibromyalgia

What they tested

The INNOVA trial randomly assigned 98 women with fibromyalgia to low-dose naltrexone 4.5 mg a day (48 women) or placebo (50 women), added to their existing treatment. Neither the women nor the researchers knew who got which.

The main outcome was the change in pain intensity on a 0–10 scale from the start to 3 months. Function, anxiety and depression, thinking problems, disability, worry and the women's own sense of change were measured at 3, 6 and 12 months.

What they found

At 3 months, pain dropped by 0.33 points with low-dose naltrexone and 0.64 points with placebo. The adjusted difference between groups was 0.49 points (p = 0.236), which was not statistically significant.

Secondary outcomes showed minor and inconsistent changes, and the share of people who responded was low and similar in both groups.

In exploratory analyses, women who believed they were getting low-dose naltrexone seemed to improve somewhat, though the effects were inconsistent.

Side effects, mostly mild and short-lived, were reported by 33 women (68.8%) on low-dose naltrexone and 36 (72%) on placebo. No treatment-related serious events occurred.

Limits

• Only women were included, all at a single centre.
• Low-dose naltrexone was tested as an add-on to other treatments, not on its own.
• With 98 women, it could miss a small effect.

What it means if you're considering naltrexone

This trial, the first to follow low-dose naltrexone in fibromyalgia for a year, adds to evidence questioning its value for this condition. Low-dose naltrexone also isn't a treatment for drinking; the site's guides note it has no evidence for alcohol use disorder.