Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study.
BACKGROUND
Clinical studies with opioid antagonists for treatment of problem drinking have mainly been conducted in specialized alcohol treatment centers, included structured psychosocial treatment, and have focused on maintaining abstinence after a period of abstinence from alcohol.


METHODS
This multisite, randomized double-blind study investigated targeted nalmefene in reducing heavy drinking. Specialized alcohol treatment centers and private general practices enrolled 403 subjects (328 men, 75 women). Subjects were instructed to take nalmefene 10 to 40 mg (n=242) or placebo (n=161) when they believed drinking to be imminent. After 28 weeks, 57 subjects from the nalmefene group continued into a 24-week randomized withdrawal extension. Concomitant psychosocial intervention was minimal and no treatment goals were imposed. Alcohol consumption was recorded using the time-line follow-back method. Biochemical indicators of alcohol use were also measured.


RESULTS
The mean monthly number of heavy drinking days (HDDs) during the 12-week period before inclusion was 15.5 (SD 6.9) in the nalmefene group and 16.2 (SD 6.9) in the placebo group. During treatment, the mean numbers of HDDs were 8.6 to 9.3 in the nalmefene group and 10.6 to 12.0 in the placebo group (p=0.0065). The levels of serum alanine aminotransferase and gamma-glutamyl transferase decreased in the nalmefene group compared with the placebo group (p=0.0088 and 0.0023). During the randomized withdrawal period, subjects randomized to placebo apparently returned to heavier drinking. Subjects receiving nalmefene reported more nausea, insomnia, fatigue, dizziness, and malaise than subjects on placebo.


CONCLUSIONS
Nalmefene appears to be effective and safe in reducing heavy drinking, even when accompanied by minimal psychosocial support.
Karhuvaara
Sakari
S
Biotie Therapies Corp, Turku, Finland. sakari.karhuvaara@pp.inet.fi
Simojoki
Kaarlo
K
Virta
Antti
A
Rosberg
Markus
M
Löyttyniemi
Eliisa
E
Nurminen
Tommi
T
Kallio
Antero
A
Mäkelä
Rauno
R
D000428:Alcohol Drinking / Q000188:drug therapy / Q000517:prevention & control* / Q000523:psychology; D000437:Alcoholism / Q000188:drug therapy / Q000523:psychology / Q000534:rehabilitation*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005387:Finland; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced; D010349:Patient Compliance; D010919:Placebos; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D016320:Substance Abuse Treatment Centers / Q000706:statistics & numerical data; D013695:Temperance / Q000523:psychology; D016896:Treatment Outcome
D009292:Narcotic Antagonists; D010919:Placebos; D009271:Naltrexone; C038981:nalmefene