High dose naltrexone for dyskinesias induced by levodopa

Area of Science:

• Neurology
• Pharmacology

Background:

• Levodopa-induced dyskinesias (LIDs) are a common motor complication in Parkinson's disease (PD).
• Naltrexone, an opioid antagonist, has been investigated for potential therapeutic effects in PD and related movement disorders.

Purpose of the Study:

• To evaluate the efficacy and tolerability of high-dose oral naltrexone in reducing LIDs in patients with Parkinson's disease.
• To assess the impact of naltrexone on motor function and 'off' time in PD patients.

Main Methods:

• A randomized, placebo-controlled, double-blind, crossover trial involving ten Parkinson's disease patients with LIDs.
• Participants received high-dose naltrexone (5 mg/kg/day) or placebo for 2.5 weeks, followed by a 1-week washout period.
• Assessments included the Unified Parkinson's Disease Rating Scale (UPDRS), Unified Dyskinesia Rating Scale (UDRS), levodopa challenge, and patient diaries.

Main Results:

• A statistically significant, yet small, reduction in LIDs was observed via patient diaries with naltrexone compared to placebo (p<0.05).
• No significant differences in LIDs were detected using objective measures or other subjective assessments.
• Naltrexone was well-tolerated, with no significant adverse effects on UPDRS motor scores or 'off' time.

Conclusions:

• Short-term therapy with high-dose oral naltrexone (250-350 mg/day) demonstrates minimal to no significant effect on reducing levodopa-induced dyskinesias in Parkinson's disease.
• Further research may be needed to explore alternative dosing strategies or patient populations for naltrexone in PD management.