Parker 2018 (Cochrane): low-dose naltrexone for Crohn's disease

What they tested

A systematic review gathers every trial on a question and pools the results. Cochrane reviewers searched for randomized trials of low-dose naltrexone (LDN) in active Crohn's disease, an inflammatory disease of the digestive tract, and found two with 46 participants in total.

One trial gave 34 adults LDN 4.5 mg a day or a placebo for 12 weeks. The other gave 12 children LDN (0.1 mg/kg, up to 4.5 mg a day) or placebo for eight weeks, mainly to check safety and tolerability.

What they found

In the adult trial, 30% (5/18) on LDN reached clinical remission at 12 weeks compared with 18% (3/16) on placebo (RR 1.48, 95% CI 0.42 to 5.24), not a statistically significant difference. In the children's trial, 25% on LDN reached remission against none on placebo, but it was unclear whether that figure came from the randomized part or an open-label extension.

Some secondary measures favoured LDN in adults. 83% (15/18) had a 70-point fall in their disease activity score at week 12, against 38% (6/16) on placebo (RR 2.22). 72% (13/18) had an endoscopic response, meaning improvement seen on a scope, against 25% (4/16) (RR 2.89).

Other results were uncertain. A 100-point response was seen in 61% (11/18) on LDN and 31% (5/16) on placebo (RR 1.96, 95% CI 0.87 to 4.42), and endoscopic remission in 22% (4/18) against 0% (0/16), neither a significant difference.

Pooled across both trials, there were no significant differences in dropouts due to side effects or in specific side effects such as sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue. Neither trial reported serious adverse events.

Limits

• Only two small trials, with 46 people in total, were found.
• The reviewers rated the overall quality of the evidence as low because the data were so sparse.
• The children's trial was mainly about safety, and it was unclear which part of it the remission result came from.

What it means if you're considering naltrexone

Low-dose naltrexone has drawn interest as a possible Crohn's treatment, but this review shows how thin the trial evidence is: one small adult trial with mixed results and one tiny children's trial. The side-effect data were reassuring, but they too came from very few people, and the reviewers call for more trials in adults and children.