OBJECTIVE: Impulse control disorders (ICDs) in Parkinson disease (PD) are common 
and can be difficult to manage. The objective of this study was to determine the 
efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment 
of ICDs in PD.
METHODS: Patients with PD (n = 50) and an ICD were enrolled in an 8-week, 
randomized (1:1), double-blind, placebo-controlled study of naltrexone 50-100 
mg/d (flexible dosing). The primary outcome measure was response based on the 
Clinical Global Impression-Change score, and the secondary outcome measure was 
change in symptom severity using the Questionnaire for Impulsive-Compulsive 
Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score.
RESULTS: Forty-five patients (90%) completed the study. The Clinical Global 
Impression-Change response rate difference favoring naltrexone in completers was 
19.8% (95% confidence interval [CI] -8.7% to 44.2%). While this difference was 
not significant (odds ratio=1.6, 95% CI 0.5-5.2, Wald χ2 [df]=0.5 [1], p=0.5), 
naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD 
score over time compared with placebo (regression coefficient for interaction 
term in linear mixed-effects model=-7.37, F[df]=4.3 [1, 49], p=0.04). The 
estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points 
(95% CI 9.9-19.9) for naltrexone and 7.5 points (95% CI 2.5-12.6) for placebo.
CONCLUSIONS: Naltrexone treatment was not efficacious for the treatment of ICDs 
in PD using a global assessment of response, but findings using a PD-specific 
ICD rating scale support further evaluation of opioid antagonists for the 
treatment of ICD symptoms in PD.
CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in 
patients with PD and an ICD, naltrexone does not significantly increase the 
probability of achieving response. However, the study lacked the precision to 
exclude an important difference in response rates.