Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial.
BACKGROUND
Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited.


OBJECTIVE
To determine efficacy and tolerability of a long-acting intramuscular formulation of naltrexone for treatment of alcohol-dependent patients.


METHODS
A 6-month, randomized, double-blind, placebo-controlled trial conducted between February 2002 and September 2003 at 24 US public hospitals, private and Veterans Administration clinics, and tertiary care medical centers. Of the 899 individuals screened, 627 who were diagnosed as being actively drinking alcohol-dependent adults were randomized to receive treatment and 624 received at least 1 injection.


METHODS
An intramuscular injection of 380 mg of long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210) or a matching volume of placebo (n = 209) each administered monthly and combined with 12 sessions of low-intensity psychosocial intervention.


METHODS
The event rate of heavy drinking days in the intent-to-treat population.


RESULTS
Compared with placebo, 380 mg of long-acting naltrexone resulted in a 25% decrease in the event rate of heavy drinking days (P = .02) [corrected] and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex and pretreatment abstinence each showed significant interaction with the medication group on treatment outcome, with men and those with lead-in abstinence both exhibiting greater treatment effects. Discontinuation due to adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and 6.7% in the placebo group. Overall, rate and time to treatment discontinuation were similar among treatment groups.


CONCLUSIONS
Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol-dependent patients during 6 months of therapy. These data indicate that long-acting naltrexone can be of benefit in the treatment of alcohol dependence.
Garbutt
James C
JC
Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill 27599-7160, USA. jc_garbutt@med.unc.edu
Kranzler
Henry R
HR
O'Malley
Stephanie S
SS
Gastfriend
David R
DR
Pettinati
Helen M
HM
Silverman
Bernard L
BL
Loewy
John W
JW
Ehrich
Elliot W
EW
D000328:Adult; D000437:Alcoholism / Q000188:drug therapy* / Q000534:rehabilitation; D004311:Double-Blind Method; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011614:Psychotherapy, Brief
D004337:Drug Carriers; D009292:Narcotic Antagonists; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D009271:Naltrexone