Naltrexone for Crohn Disease

Zara M. Risoldi Cochrane, PharmD

Disclosures

January 05, 2016

Question

Is the use of low-dose naltrexone effective in the treatment of Crohn disease?

Zara M. Risoldi Cochrane, PharmD
Associate Professor of Pharmacy Practice, Creighton University School of Pharmacy and Health Professions; Associate Director, Center for Drug Information and Evidence-Based Practice, Omaha, Nebraska

Crohn disease is a chronic inflammatory disease of the gastrointestinal tract that causes abdominal cramps and pain, persistent diarrhea, rectal bleeding, constipation, and weight loss.[1] Although the exact etiology of Crohn disease is unknown, treatment typically includes agents used to reduce the inflammatory response, such as 5-aminosalicylates, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha biologic agents.[1,2]

Naltrexone is an opioid receptor antagonist approved for the treatment of alcohol and opioid dependence disorders. But because of emerging evidence that suggests opioid peptides can regulate immune responses and inflammation, clinicians are considering whether off-label use of low-dose naltrexone can be valuable in the management of Crohn disease.[3]

The safety and effectiveness of naltrexone in adults with active Crohn disease have been evaluated in two small clinical studies.[3,4] In each, patients who received 4.5 mg of naltrexone daily for 12 weeks had significant improvements in their symptom scores. Between 80% and 90% of patients were considered responders to naltrexone therapy, defined as having a 70-point decrease on the Crohn Disease Activity Index (CDAI).[3,4] A pilot study in children with moderate to severe Crohn disease showed similar positive results, although CDAI response rates were a bit lower (around 67%).[5]

Adverse reactions seen across the clinical trials include fatigue and sleep disturbances (eg, insomnia), and patients should be advised to take this medication in the morning. Gastrointestinal symptoms also occurred but were probably due to the Crohn disease itself and not the naltrexone treatment.

Although these results seem promising, there are several important caveats to consider. Together, the studies represent the experience of fewer than 70 patients, and whether the same therapeutic benefits will be seen in a larger population or in different presentations of Crohn disease is unclear. Larger trials are also needed to better characterize the safety profile of naltrexone in Crohn disease.

Patients who were studied in the available trials maintained treatment with other Crohn disease medications, such as aminosalicylates, corticosteroids, and immunomodulators. The use of low-dose naltrexone as monotherapy has not been studied, and no information is available about using naltrexone in combination with anti-tumor necrosis factor alpha agents.

Finally, oral tablets of naltrexone are available commercially only in a 50-mg strength. To replicate the 4.5-mg dose used in trials, low-dose naltrexone would need to be specially compounded.

Naltrexone is not included in current treatment guidelines for Crohn disease from the American Gastroenterological Association or the American College of Gastroenterology.[2,6] Although low-dose naltrexone may offer benefit as adjunctive therapy in patients with active Crohn disease, this treatment remains investigational owing to limited supporting evidence.

The author wishes to acknowledge Natalie Fukuhara, PharmD candidate 2016, for her contribution to the literature search.

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