Naltrexone alone and with sertraline for the treatment of alcohol dependence in Alaska natives and non-natives residing in rural settings: a randomized controlled trial.
BACKGROUND
Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. An exploratory aim examined whether the Asn40Asp polymorphism of the mu-opioid receptor gene (OPRM1) predicted response to naltrexone, as had been reported in Caucasians.


METHODS
Randomized, controlled trial enrolling 101 Alaskans with alcohol dependence, including 68 American Indians/Alaska Natives. Participants received 16 weeks of either (1) placebo (placebo naltrexone + placebo sertraline), (2) naltrexone monotherapy (50 mg naltrexone + sertraline placebo) and (3) naltrexone + sertraline (100 mg) plus nine sessions of medical management and supportive advice. Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence.


RESULTS
Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day (p = 0.093). On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent (p = 0.024) and drinking-related consequences (p = 0.02). Combined sertraline and naltrexone did not differ from naltrexone alone. The pattern of findings was generally similar for the American Indian/Alaska Native subsample. Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele. There was a small number of Asp40 carriers, precluding statistical testing of the effect of this allele on response.


CONCLUSIONS
Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism.
O'Malley
Stephanie S
SS
Yale University School of Medicine, Connecticut Mental Health Center, S202, 34 Park Street, New Haven, CT 06519, USA. stephanie.omalley@yale.edu
Robin
Robert W
RW
Levenson
Aryeh L
AL
GreyWolf
Iva
I
Chance
Lawrence E
LE
Hodgkinson
Colin A
CA
Romano
Denise
D
Robinson
Jane
J
Meandzija
Boris
B
Stillner
Verner
V
Wu
Ran
R
Goldman
David
D
D000328:Adult; D000413:Alaska; D000437:Alcoholism / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007198:Indians, North American; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D017450:Receptors, Opioid, mu / Q000235:genetics; D012424:Rural Population; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D020280:Sertraline / Q000008:administration & dosage / Q000627:therapeutic use*
D009271:Naltrexone; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C485764:OPRM1 protein, human