For patients with incurable diseases such as Crohn’s disease, new treatments to help maintain symptom remission can provide hope for living a more comfortable life. One proposed treatment under investigation for Crohn’s disease is low dose naltrexone (LDN). Its use in treating Crohn’s disease remains controversial due to the small number of studies that have been conducted and their inconclusive results.
Low dose naltrexone, named as such because it is given in 4.5 mg doses, is an off-label use of naltrexone, an opioid receptor antagonist. According to Crohn’s Forum, chronic administration of opioids inhibits the normal immune response and enhances pro-inflammatory cytokine production. Naltrexone can reverse these immunosuppressive effects by blocking opioid receptors.
Since Crohn’s disease is a type of inflammatory bowel disease, researchers have been interested in administering LDN to combat inflammation in patients. An open-label pilot prospective trial published in The American Journal of Gastroenterology, entitled, “Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease,” by a research group led by Jill Smith, MD, and Ian Zagon, PhD, at Pennsylvania State University first investigated the safety and efficacy of LDN in patients with active Crohn’s disease.
Seventeen patients were studied for twelve weeks while using 4.5 mg naltrexone daily. Inflammatory bowel disease questionnaires (IBDQs), short-form (SF-36) quality of life surveys, and Crohn’s disease activity index (CDAI) scores were assessed before the study, every four weeks during the study, and four weeks past the study.
As a result of LDN treatment, CDAI scores decreased significantly and remained lower than baseline at four weeks beyond the study. Nearly all (89%) of the patients responded to treatment, and 67% achieved remission. No adverse events occurred, and the most common side effect was sleep disturbance.
In addition to this study, two randomized controlled trials of LDN were reviewed by an article published in The Cochrane Library entitled, “Low Dose Naltrexone for Induction of Remission in Crohn’s Disease.” One study evaluated 34 adult patients (18 on 4.5 mg/day LDN and 16 on placebo) to identify safety and efficacy of LDN over 12 weeks, and the other study evaluated 12 pediatric patients for eight weeks to determine the safety and tolerability of LDN.
The studies yielded mixed results. On one hand, a significant difference in clinical response rate was observed for adult LDN patients compared to placebo patients, but on the other, there was no significant difference in remission (neither clinical nor endoscopic). For the pediatric patients, 25% of LDN treated patients achieved clinical remission, while none of the placebo treated patients achieved clinical remission. Looking at both adult and pediatric patients, no serious adverse events were reported.
Evidently, there is insufficient information to determine the efficacy of LDN in patients with active Crohn’s disease. GRADE analyses of the two studies suggested low quality of evidence due to small amounts of data.
To mitigate these inadequacies, a clinical trial has been registered by Santa Barbara Cottage Hospital under the official title, “Low Dose Naltrexone in Symptomatic Inflammatory Bowel Disease,” but is not recruiting. The primary goal of the phase 4 study is to compare LDN against placebo in patients with inflammatory bowel disease, Crohn’s disease, or ulcerative colitis. Efficacy of treatment will be determined by the IBDQ.
It is vital to continue to investigate LDN in patients with Crohn’s disease to establish the safety and efficacy of this off-label medication. Results so far suggest a potential of LDN, but validation is necessary.
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