A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence.
The opiate antagonist nalmefene has been shown in 2 single-site studies to reduce alcohol consumption and relapse drinking in alcohol-dependent individuals. This safety and preliminary multisite efficacy study evaluated 3 doses of nalmefene (5, 20, or 40 mg) in a double-blind comparison to placebo over a 12-week treatment period in 270 recently abstinent outpatient alcohol-dependent individuals. Participants concomitantly received 4 sessions of a motivational enhancement therapy (with a medication compliance component) delivered from trained counselors. Although more subjects in the active medication groups terminated the study early secondary to adverse events, the rates did not differ significantly from that of placebo. The 20-mg/d group experienced more insomnia, dizziness, and confusion, while the 5-mg group also had more dizziness and the 40-mg group had more nausea than the placebo group. Most of these symptoms were mild and improved over time. Although all subjects had a reduction in heavy drinking days, craving, gamma-glutamyl transferase, and carbohydrate-deficient transferrin concentrations over the course of the study, there was no difference between the active medication and placebo groups on these measures. The time to first heavy drinking day was also not significantly different between the placebo and the active treatment groups. This relatively small multisite trial showed that nalmefene was reasonably well tolerated in recently abstinent alcoholics. However, possibly because of variation among the sites or the comparatively small sample size, there was no evidence of superior efficacy outcomes with nalmefene treatment.
Anton
Raymond F
RF
Medical University of South Carolina, Charleston, SC 29425, USA. antonr@musc.edu
Pettinati
Helen
H
Zweben
Allen
A
Kranzler
Henry R
HR
Johnson
Bankole
B
Bohn
Michael J
MJ
McCaul
Mary E
ME
Anthenelli
Robert
R
Salloum
Ihsan
I
Galloway
Gantt
G
Garbutt
James
J
Swift
Robert
R
Gastfriend
David
D
Kallio
Antero
A
Karhuvaara
Sakari
S
D000328:Adult; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D009271:Naltrexone; C038981:nalmefene