The Cochrane review of low dose naltrexone (LDN) in Crohn's disease concluded that currently there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of LDN. It covered 2 small randomized trials with 46 participants in total: one in adults (4.5 mg/day) and one in children (0.1 mg/kg, maximum 4.5 mg/day). LDN is an off-label use.
What the Cochrane review looked at
| Question | What the source says |
|---|---|
| Adult study | The review describes 12 weeks of LDN (4.5 mg/day) versus placebo in adult patients (N = 34). |
| Pediatric study | The review describes 8 weeks of LDN (0.1 mg/kg, maximum 4.5 mg/day) versus placebo in pediatric patients (N = 12). |
| Adult result | The review reports clinical remission at 12 weeks in 30% (5/18) of LDN treated patients versus 18% (3/16) of placebo patients, a difference that was not statistically significant (RR 1.48, 95% CI 0.42 to 5.24). |
| Side effects | The review says pooled data from both studies show no statistically significant differences in withdrawals due to adverse events or specific adverse events including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue. No serious adverse events were reported in either study. |
The sources used here do not say how the review's counts (34 adults, 12 children) relate to the numbers enrolled in the trial abstracts below (40 adults, 14 children).
The individual trials
- 2007 open-label pilot (American Journal of Gastroenterology): 17 patients with active Crohn's disease took 4.5 mg naltrexone/day for 12 weeks. The abstract reports that 89% of patients exhibited a response to therapy and 67% achieved a remission (P < 0.001). It also reports no laboratory abnormalities and sleep disturbances as the most common side effect, occurring in 7 patients. An open-label study cannot show cause and effect.
- 2011 randomized trial (Digestive Diseases and Sciences): 40 adults with active Crohn's disease were randomized to daily oral 4.5-mg naltrexone or placebo in a 12-week, double-blind, placebo-controlled trial. The abstract reports that 88% of those treated with naltrexone had at least a 70-point decline in CDAI scores compared to 40% of placebo-treated patients (p = 0.009). That outcome is worded differently from the review's clinical remission figure above.
- 2013 pediatric pilot (Journal of Clinical Gastroenterology): 14 children (mean age 12.3 years, range 8 to 17 y) were randomized to placebo or naltrexone (0.1 mg/kg) orally for 8 weeks, followed by open-labeled treatment with 8 additional weeks of naltrexone. The open-labeled weeks cannot show cause and effect. The abstract reports that oral naltrexone was well tolerated without any serious adverse events in children with moderate to severe Crohn's disease.
Disclosures in the sources
- The 2011 randomized trial's conflict-of-interest statement discloses that two of its authors have intellectual property rights and have a patent for the use of naltrexone in inflammatory bowel disease (IBD).
- The 2013 pediatric pilot's conflict-of-interest statement discloses that one author has intellectual property rights and is a co-inventor on a US patent for the use of naltrexone in IBD.
- The Cochrane review's conflict of interest statement discloses that one person named in it has received fees for consultancy from AbbVie, Ferring, Janssen, Takeda, Lupin, Shire and Allergan and speakers' fees from AbbVie, Takeda, Shire and Allergan, and that all of these financial activities are outside the submitted work.
These are disclosures, not findings about the results. This guide has no disclosure statement for the 2007 open-label pilot.
What this does not tell you
These are descriptions from abstracts. The Cochrane review found insufficient evidence for firm conclusions about efficacy and safety, and the studies were small. The 2007 pilot was open-label, so it cannot show cause and effect. A finding of no statistically significant difference in small studies does not show that side effects are absent.
Adults took 4.5 mg daily and children took 0.1 mg/kg, so the doses differ, and a result in one age group does not apply to the other. A result in Crohn's disease does not apply to other conditions. A licensed provider decides whether LDN is appropriate for a person.