OBJECTIVE: Pathological gambling is a disabling disorder experienced by 
approximately 1%-2% of adults and for which there are few empirically validated 
treatments. The authors examined the efficacy and tolerability of the opioid 
antagonist nalmefene in the treatment of adults with pathological gambling.
METHOD: A 16-week, randomized, dose-ranging, double-blind, placebo-controlled 
trial was conducted at 15 outpatient treatment centers across the United States 
between March 2002 and April 2003. Two hundred seven persons with DSM-IV 
pathological gambling were randomly assigned to receive nalmefene (25 mg/day, 50 
mg/day, or 100 mg/day) or placebo. Scores on the primary outcome measure 
(Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling) were 
analyzed by using a linear mixed-effects model.
RESULTS: Estimated regression coefficients showed that the 25 mg/day and 50 
mg/day nalmefene groups had significantly different scores on the Yale-Brown 
Obsessive Compulsive Scale Modified for Pathological Gambling, compared to the 
placebo group. A total of 59.2% of the subjects who received 25 mg/day of 
nalmefene were rated as "much improved" or "very much improved" at the last 
evaluation, compared to 34.0% of those who received placebo. Adverse experiences 
included nausea, dizziness, and insomnia.
CONCLUSIONS: Subjects who received nalmefene had a statistically significant 
reduction in severity of pathological gambling. Low-dose nalmefene (25 mg/day) 
appeared efficacious and was associated with few adverse events. Higher doses 
(50 mg/day and 100 mg/day) resulted in intolerable side effects.