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Low-Dose Naltrexone's Tolerability and Effects in Fatigued Patients with Parkinson's Disease: An Open-Label Study

Low-Dose Naltrexone's Tolerability and Effects in Fatigued Patients with Parkinson's Disease: An Open-Label Study
Publication Type
Research Type
Reported as
Clinical Trial
July 01, 2010
Thomas Guttuso Jr., Naomi Salins, David Lichter
The State University of New York at Buffalo

INTRODUCTION: One third of idiopathic Parkinson's disease (IPD) patients report fatigue as their most disabling symptom, and 58% consider fatigue to be one of their three most disabling symptoms. The use of Low-Dose Naltrexone (LDN), 4.5 mg qhs, has been anecdotally reported to improve fatigue in IPD.

METHODS: We are examining the tolerability and effectiveness of LDN in patients with parkinsonism in an ongoing open-label trial. Fatigue and motor symptoms in the “On” state are being assessed at baseline and every 4 months over 1 year using the Parkinson Fatigue Scale (PFS-16) and the Unified Parkinson's Disease Rating Scale (UPDRS), respectively. Global Satisfaction of Treatment is also being assessed. We report here on the changes in fatigue and motor scores among the 4 IPD subjects who were fatigued at baseline, defined as a score of e 53 on the PFS-16. We also compare the fatigue changes with those from previous trials in fatigued IPD and multiple sclerosis (MS) patients.

RESULTS: Eight subjects have been enrolled since January 2009. The 4 IPD subjects who were fatigued at baseline have experienced a mean 22% reduction in PFS-16 scores (range 13–30%) and a 15% increase in total UPDRS “On” scores after 8 months of LDN therapy. Mean Global Satisfaction of Treatment at 8 months was 8.75 on the 10-point scale. No side effects have been associated with LDN therapy among the 8 subjects. Based on previous randomized controlled trials (RCTs), the only effective therapy for fatigue in IPD has been methylphenidate, which showed a 16% decrease in fatigue from baseline. The three therapies demonstrating effectiveness in treating fatigue in MS patients in RCTs have been amantadine, modafinil, and aspirin, which decreased fatigue by 24%, 20%, and 18% from baseline, respectively. Modafinil was shown to be ineffective in treating fatigue in IPD.

CONCLUSIONS: In this small, open-label trial, LDN therapy was well tolerated and was associated with equivalent reductions in fatigue compared with historical benchmarks. These observed reductions in fatigue are unlikely to have been a function of any perceived improvements to motor symptoms, because UPDRS scores slightly worsened over the 8-month trial, as expected in this progressive disease.