Moderators of naltrexone's effects on drinking, urge, and alcohol effects in non-treatment-seeking heavy drinkers in the natural environment.
BACKGROUND
Naltrexone (NTX) has proven to be effective with alcoholics in treatment, with most controlled clinical trials showing beneficial effects on heavy drinking rates. However, little is known about the behavioral mechanisms underlying the effects of NTX on drinking, or about patient characteristics that may moderate NTX's effects on drinking. In this study, ecological momentary assessment (EMA) techniques were used to investigate some of the putative mechanisms of naltrexone's effects on drinking in heavy drinkers who were not seeking treatment for alcohol problems. Polymorphisms in the D4 dopamine receptor (DRD4) gene and the mu-opiate receptor (OPRM1) gene, family history of alcohol problems, age of onset of alcoholism and gender were explored as potential moderators of NTX's effects.


METHODS
After a 1-week placebo lead-in period, heavy drinkers (n = 180), 63% of whom were alcohol-dependent, were randomized to 3 weeks of daily naltrexone (50 mg) or placebo. Throughout the study, participants used EMA on palm-pilot computers to enter, in real time, drink data, urge levels, and subjective effects of alcohol consumption.


RESULTS
Naltrexone reduced percentage drinking days in all participants and reduced percent heavy drinking days in DRD4-L individuals; NTX decreased urge levels in participants with younger age of alcoholism onset; NTX increased time between drinks in participants who had more relatives with alcohol problems; and NTX reduced the stimulating effects of alcohol in women. OPRM1 status did not moderate any of NTX's effects.


CONCLUSIONS
These results confirm earlier findings of NTX's effects on drinking and related subjective effects, and extend them by describing individual difference variables that moderate these effects in the natural environment, using data collected in real time.
Tidey
Jennifer W
JW
Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island 02912, USA. jennifer_tidey@brown.edu
Monti
Peter M
PM
Rohsenow
Damaris J
DJ
Gwaltney
Chad J
CJ
Miranda
Robert
R
McGeary
John E
JE
MacKillop
James
J
Swift
Robert M
RM
Abrams
David B
DB
Shiffman
Saul
S
Paty
Jean A
JA
D000328:Adult; D017668:Age of Onset; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D000437:Alcoholism / Q000235:genetics; D004777:Environment; D005260:Female; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010349:Patient Compliance; D020641:Polymorphism, Single Nucleotide; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D015203:Reproducibility of Results; D012737:Sex Factors; D013997:Time Factors
C493599:DRD4 protein, human; D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D050638:Receptors, Dopamine D4; D009271:Naltrexone