Retrospective Chart Review of MS Patients Receiving Low Dose Naltrexone to Assess Safety, Tolerability, and Effect on Fatigue

Background: A significant but unknown number of patients in the United States with multiple sclerosis have been using Low-Dose Naltrexone prepared by Compounding Pharmacies.  The exact number of individuals using the LDN has never been established but there are numerous Internet websites that have established a subculture of patients with multiple sclerosis who have claimed its benefits. 

LDN’s transient blockade of the opioid receptors upregulates the production of both endogenous opioids and the classical and non-classical opioid receptors. The non-classical opioid receptor enhances the body’s ability to regulate cell proliferation, specifically T-cells and B-cells causing autoimmune damage to the CNS. In a recently published preclinical experiment, met-enkephalin, also known as Opioid Growth Factor (OGF), was shown to be the peptide upregulated by the LDN’s transient blockade of the receptor. OGF demonstrated a significant biological and clinical effect on murine experimental autoimmune encephalitis (EAE) models. This EAE model is the industry standard for evaluating preclinical effectiveness of potential MS therapies. If proven effective in delaying the progression of MS in the clinical setting, LDN would change the paradigm of MS treatment in terms of mode of delivery, cost, and safety.

Objectives: This study investigated the safety, tolerability, and benefits to fatigue of LDN on patients with MS. It will focus on the number of patients who stopped taking LDN and the reasons for why they stopped the drug. This paper also studies the frequency and variety of side effects that were reported to be specific to their LDN use.

Methods: A retrospective review was performed on 435 patient charts seen in an out-patient Multiple Sclerosis (MS) clinic between 1/1/2005 and 5/31/2012.  There were 215 MS patients having exposure to Low Dose Naltrexone (LDN) and they served as the study group.  Patients were offered LDN as an adjunctive therapy to patients who reported significant fatigue as an MS symptom (no other medical cause), or who were not interested in any of the injectable MS treatments, or reported severe needle-phobia.  Several patients were diagnosed as having a Clinically Isolated Syndrome, by the 2001 McDonald criteria in place at that time, and, who declined an injectable therapy, were offered LDN. Patients were offered the LDN as a medication with the understanding they could stop medication if they felt little benefit or had side effects. 

Results: Results of the study supported LDN use as a safe, well-tolerated, and inexpensive therapy when either used alone or added to existing modes of MS treatment.   

Conclusions: This retrospective chart review may offer support towards a future prospective double-blind placebo study, or potential studies as combination LDN + disease modifying therapy (DMT) vs DMT.