The Effect of Low-Dose Naltrexone on Medication in Inflammatory Bowel Disease: A Quasi Experimental Before-and-After Prescription Database Study

Abstract

Background and aims: Low-dose naltrexone [LDN] is a controversial off-label treatment used by many Crohn's disease [CD] and ulcerative colitis [UC] patients. A small number of preliminary studies indicate that LDN might be beneficial in CD, but evidence is too scarce to demonstrate efficacy. We sought to examine whether initiation of LDN therapy by patients with inflammatory bowel disease [IBD] was followed by changes in dispensing of relevant medication.

Methods: We performed a quasi-experimental before-and-after study following a sudden increase in LDN use in the Norwegian population in 2013. IBD patients were identified from among all the patients who had at least one LDN prescription recorded in the Norwegian Prescription Database [NorPD] in 2013. Drug dispensing 2 years before and after the first LDN prescription was compared.

Results: We identified 582 IBD patients who had received LDN. Of the 256 patients who became persistent LDN users, there were reductions in the number of users for [i] all examined drugs [-12%], [ii] intestinal anti-inflammatory agents [-17%], [iii] other immunosuppressants [-29%], [iv] intestinal corticosteroids [-32%] and [v] aminosalicylates [-17%]. In subgroups of identified CD and UC patients, there were significant reductions in the number of users of intestinal corticosteroids [CD: -44%, UC: -53%] and systemic corticosteroids [UC: -24%]. No significant differences in cumulative defined daily doses were observed.

Conclusions: Our findings imply that the initiation of LDN in IBD is followed by reduced dispensing of several drugs considered essential in the treatment of CD and UC.

Figure 1.

Flowchart showing the inclusion of study subjects. Outcomes were analyzed separately in identified inflammatory bowel disease [IBD], Crohn’s disease and ulcerative colitis patients.

Figure 2.

Cumulative average defined daily doses [DDDs] of all drugs being studied by time before and after the first low-dose naltrexone [LDN] prescription. Solid lines show cumulative consumption for the 730 days preceding the first LDN dose, and dashed lines after.

Figure 3.

Cumulative average defined daily doses [DDDs] of systemic immunosuppressants throughout the entire 4-year observation period. The first LDN prescription was dispensed at time = 0. The sum of systemic corticosteroids, tumor necrosis factor α, mercaptopurine, methotrexate, azathioprine, cyclosporine and tacrolimus is displayed.

Figure 4.

Cumulative average defined daily doses [DDDs] of intestinal anti-inflammatory agents throughout the entire 4-year observation period. The first LDN prescription was dispensed at time = 0. The sum of aminosalicylates and intestinal corticosteroids is displayed.