Hegde 2025: low-dose naltrexone for chronic pain, a meta-analysis

What they tested

A meta-analysis pools the results of many trials. The authors searched PubMed, Embase, Scopus, Cochrane and trial registries and included seven randomized trials of low-dose naltrexone for chronic pain syndromes.

They compared changes in pain scores using a standardized effect size (Cohen's d), looked separately by condition and by comparator (placebo or an active drug), and compared side-effect rates. They also rated risk of bias and the certainty of the evidence.

What they found

Overall, low-dose naltrexone showed no significant difference in pain response compared with control groups (d = -0.11; 95% CI -0.96 to 0.74; P = 0.31).

In fibromyalgia, it improved pain compared with placebo (d = -0.34; 95% CI -0.62 to -0.06). Against active comparator drugs it showed no difference (d = 0.67; P = 0.35).

Side effects were more common with low-dose naltrexone than with placebo (IRR 1.4; 95% CI 1.12 to 1.75), meaning about 1.4 times the rate, and comparable to active comparators (IRR 0.55; P = 0.65).

The authors concluded that low-dose naltrexone is better than placebo for fibromyalgia pain and similar to active controls in chronic pain.

Limits

• Only seven trials were included, spread across different pain conditions.
• The abstract doesn't give the doses, trial sizes or certainty ratings, so it's hard to judge how much weight each result deserves.

What it means if you're considering naltrexone

The overall picture is mixed: no clear benefit for chronic pain as a whole, a small benefit over placebo in fibromyalgia, and more side effects than placebo. Low-dose naltrexone is an off-label use for pain and is separate from naltrexone for alcohol, which this review doesn't address.