The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking.
BACKGROUND
In almost 2 decades of naltrexone research for treating alcoholism, there have been 29 published randomized placebo-controlled trials of opioid antagonists, primarily naltrexone, for the treatment of alcohol dependence. The present review builds on prior systematic reviews while maximizing the number of included studies to date, for the purpose of resolving inconsistencies in naltrexone's reported efficacy across trials. Clinical trial results in this article are evaluated by the type of outcome measure used to determine naltrexone's treatment advantage, that is, measures related to reducing heavy drinking versus those related to increasing abstinence.


METHODS
We conducted a Medline search to identify double-blind studies from 1990 to the present (2006) that evaluated the use of anopiate antagonist for the treatment of alcohol dependence. There were 29 studies identified, representing 5997 alcohol-dependent patients, which met our study inclusion criteria for this review. Studies were evaluated in this review on 4 prespecified drinking outcomes-2 related to "any drinking" and 2 related to "heavy or excessive drinking."


RESULTS
In the treatment of alcohol dependence, we found that 19 (70%) of 27 clinical trials that measured reductions in "heavy or excessive drinking" demonstrated an advantage for prescribing naltrexone over placebo, whereas only 9 (36%) of 25 clinical trials that measured abstinence or "any drinking" found an advantage for medication over placebo.


CONCLUSIONS
The majority of double-blind clinical trials in the literature favored prescribing naltrexone for alcohol dependence to reduce heavy drinking. This finding is consistent with our understanding of naltrexone's mechanism of action of decreasing excessive drinking by reducing the reward associated with drinking alcohol. Thus, we conclude that outcome measures related to heavy or excessive drinking are most relevant to defining naltrexone's therapeutic effects. Factors influencing naltrexone response (treatment adherence and distinct patient subgroups) are also discussed.
Pettinati
Helen M
HM
Center for the Study of Addictions, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6178, USA. Pettinati_H@mail.trc.upenn.edu
O'Brien
Charles P
CP
Rabinowitz
Amanda R
AR
Wortman
Shoshana P
SP
Oslin
David W
DW
Kampman
Kyle M
KM
Dackis
Charles A
CA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D049673:History, 20th Century; D006801:Humans; D008875:Middle Aged; D009271:Naltrexone / Q000266:history / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000266:history / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012107:Research Design; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D009292:Narcotic Antagonists; D009271:Naltrexone