Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study

Abstract

In recent years, low dose naltrexone (LDN) has been used as an off-label therapy for several chronic diseases. Results from small laboratory and clinical studies indicate some beneficial effects of LDN in autoimmune diseases, but clinical research on LDN in rheumatic disease is limited. Using a pharmacoepidemiological approach, we wanted to test the hypothesis that starting LDN leads to reduced dispensing of medicines used in the treatment of rheumatic disease. We performed a controlled before-after study based on the Norwegian Prescription Database (NorPD) to compare prescriptions to patients one year before and one year after starting LDN in 2013. The identified patients (n = 360) were stratified into three groups based on LDN exposure. Outcomes were differences in dispensing of medicines used in rheumatic disease. In persistent LDN users, there was a 13% relative reduction in cumulative defined daily doses (DDD) of all medicines examined corresponding to -73.3 DDD per patient (95% CI -120,2 to -26.4, p = 0.003), and 23% reduction of analgesics (-21.6 DDD (95% CI -35.5 to -7.6, p<0.009)). There was no significant DDD change in patients with lower LDN exposure. Persistent LDN users had significantly reduced DDDs of NSAID and opioids, and a lower proportion of users of DMARDs (-6.7 percentage points, 95% CI -12.3 to-1.0, p = 0.028), TNF-α antagonists and opioids. There was a decrease in the number of NSAID users among patients with the least LDN exposure. Important limitations are that prescription data are proxies for clinical effects and that a control group unexposed to LDN is lacking. The results support the hypothesis that persistent use of LDN reduces the need for medication used in the treatment of rheumatic and seropositive arthritis. Randomised clinical trials on LDN in rheumatic disease are warranted.

Partial Response of Alopecia Areata to Helicobacter Pylori Eradication and Treatment with Low-Dose Naltrexone

“…There is no scientific evidence regarding the use of naltrexone in the treatment of alopecia areata. The mechanism of action of naltrexone prompted us to postulate that it could be equally beneficial in our patient since it has been shown to be helpful in other autoimmune diseases [3,5].…”

“…There is scientific evidence of the usefulness of naltrexone in low doses (an opioid antagonist) in autoimmune diseases such as inflammatory bowel disease [3] or chronic genetic skin diseases such as familial benign pemphigus (Hailey-Hailey disease) [4]. Earlier studies have also shown some effectiveness in the treatment of rheumatoid and seropositive arthritis (showing a reduction in medication use in patients taking low-dose naltrexone) [5].…”

“…Unlike the FDA-approved dose of naltrexone of 50 mg/day that antagonizes opioid receptors, low dose of naltrexone (less than 10 mg/day, usually 0.1 mg/kg/day) has been shown to have antiinflammatory properties possibly through its action on Toll-like receptors (by selective blockade of opioid receptors on inflammatory cells peripherally through antagonism on Toll-like receptor 4) [6,7] and also by inducing an elevation of endogenous opioids such as endorphins and enkephalins [3]. Naltrexone interacts with the opioid growth factor receptor (OGFr) on immune cells directly as an antagonist or modulates the amount of OGFr agonists like met-enkephalin, thus helping in the minimization of the exaggerated autoimmune response [5]. As it is a nonselective opioid receptor antagonist, it also interacts with other opioid receptors such as mu, kappa, and delta.…”

Changes in the consumption of antiepileptics and psychotropic medicines after starting low dose naltrexone: A nation-wide register-based controlled before-after study

“…A sudden and large increase in LDN consumption in Norway during 2013 10 has enabled nationwide quasi-experimental register studies on change in medicine use associated to initiation of LDN use. Previously we have demonstrated an association between starting LDN and changes in medication for inflammatory bowel disease 11 and rheumatoid and seropositive arthritis 12 , but not in multiple sclerosis 13 . We have shown almost halving of the opioid consumption among persistent LDN users 14 .…”

Low-dose naltrexone as a treatment for chronic fatigue syndrome

“…Small-scale clinical trials of LDN in multiple sclerosis, HIV, fibromyalgia, Gulf War Illness and Crohn’s disease have shown proof-of-concept efficacy and/or low toxicity 21–28. Recent before-and-after cohort studies of patients with Crohn’s disease and rheumatoid arthritis in Norway showed reductions in prescriptions for disease-modifying medications after starting LDN 29 30. We know of no clinical trials of naltrexone in patients with chronic fatigue syndrome or myalgic encephalomyelitis, although some patients report benefits 31.…”