***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This study compared the effects of nefazodone , a serotonergic antidepressant , with the opioid antagonist naltrexone , and an inactive placebo in 183 alcohol-dependent subjects receiving weekly relapse prevention psychotherapy . Following a single-blind , placebo lead-in period , subjects were r and omly assigned to receive study medication , which they took under double-blind conditions for 11 weeks . Naltrexone treatment was associated with significantly more adverse neuropsychiatric and gastrointestinal effects , poorer compliance , and a greater rate of treatment attrition . There were no reliable between-group differences in drinking behavior . These results indicate that nefazodone is not efficacious for treatment of alcohol dependence . Furthermore , the clinical utility of naltrexone seems to be limited by its adverse effects , a finding that has important implication s for efforts to develop medications to treat alcohol dependence AIMS To determine the clinical ly ascertained variables that are related to satisfactory response to naltrexone ( NTX ) treatment of alcohol dependence after detoxification . METHODS The use of intake and outcome variables were measured in a r and omized 3-month open-controlled trial comparing the effects of naltrexone plus psychotherapy treatment versus psychotherapy treatment alone on the maintenance of abstinence in the final 28 days ( n = 336 , all male ) . RESULTS Predictors of a positive response to NTX treatment were family history of alcoholism ( P = 0.010 ) , early age at onset of drinking problems  ( P = 0.014 ) and comorbid use of other drugs of abuse ( P < 0.001 ) . Among the subjects not treated with NTX , the greater the number of predictor variables , the lower the final 28 days abstinence rates ( P = 0.00003 ) , but this was not the case in patients treated with NTX ( P = 0.844 ) . CONCLUSIONS Patients with these features , suggesting biological vulnerability overall have poorer outcomes , but this can be reduced with NTX treatment . The type of alcoholism should be considered before deciding on the pharmacological strategy 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 r and omized 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 CONTEXT Alcohol dependence treatment may include medications , behavioral therapies , or both . It is unknown how combining these treatments may impact their effectiveness , especially in the context of primary care and other nonspecialty setting s. OBJECTIVES To evaluate the efficacy of medication , behavioral therapies , and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age , 44 years ) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnoses of primary alcohol dependence . INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d ) or acamprosate ( 3 g/d ) , both , and /or both placebos , with or without a combined behavioral intervention ( CBI ) . A ninth group received CBI only ( no pills ) . Patients were also evaluated for up to 1 year after treatment . MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day . RESULTS All groups showed substantial reduction in drinking . During treatment , patients receiving naltrexone plus medical management ( n = 302 ) , CBI plus medical management and placebos ( n = 305 ) , or both naltrexone and CBI plus medical management ( n = 309 ) had higher percent days abstinent ( 80.6 , 79.2 , and 77.1 , respectively ) than the 75.1 in those receiving placebos and medical management only ( n = 305 ) , a significant naltrexone x behavioral intervention interaction ( P = .009 ) . Naltrexone also reduced risk of a heavy drinking day ( hazard ratio , 0.72 ; 97.5 % CI , 0.53 - 0.98 ; P = .02 ) over time , most evident in those receiving medical management but not CBI . Acamprosate showed no significant effect on drinking vs placebo , either by itself or with any combination of naltrexone , CBI , or both . During treatment , those receiving CBI without pills or medical management ( n = 157 ) had lower percent days abstinent ( 66.6 ) than those receiving placebo plus medical management alone ( n = 153 ) or placebo plus medical management and CBI ( n = 156 ) ( 73.8 and 79.8 , respectively ; P<.001 ) . One year after treatment , these between-group effects were similar but no longer significant . CONCLUSIONS Patients receiving medical management with naltrexone , CBI , or both fared better on drinking outcomes , whereas acamprosate showed no evidence of efficacy , with or without CBI . No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management . Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment . Naltrexone with medical management could be delivered in health care setting s , thus serving alcohol-dependent patients who might otherwise not receive treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00006206 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 setting s. 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 R and omized , 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 sub sample .  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 Given the evidence from retrospective studies indicating that alcohol-dependent patients with homozygous or heterozygous A118 G variant of the & mgr;-opioid receptor , OPRM1 , gene have significantly better outcomes when treated with naltrexone ; this study examined this prospect ively in 100 alcohol-dependent participants prescribed naltrexone for 12 weeks and offered six sessions of cognitive-behavioral therapy or intervention . Comparisons were made among OPRM1 genotypic groups on several outcome measures . Naltrexone treatment produced significant decreases in self-reported and objective indicators of alcohol use and craving from baseline ( P<0.0001 and 0.017 , respectively ) , particularly during the first 2 months of treatment , with 68 % completing the study . However , there was no evidence of a significant association between OPRM1 A118 G genotype and treatment success on any of the outcome measures . Therefore , while naltrexone was an effective treatment for alcohol dependence , the OPRM1 A118 G genotype was not a predictor of success Naltrexone has repeatedly been shown to reduce drinking in alcohol-dependent patients . Previous clinical research suggests that naltrexone may be more effective at reducing drinking among patients with high levels of alcohol craving at the beginning of treatment . In addition , laboratory studies suggest that naltrexone may be more efficacious among patients with a high familial loading of alcohol problems . We explored both of these possibilities in the context of the first 12-week phase of a double blind , placebo-controlled naltrexone trial . A total of 121 patients were r and omized to receive 100 mg/day naltrexone and 62 patients were r and omized to receive placebo .  Both naltrexone and placebo were given in conjunction with a psychosocial intervention design ed to be integrated with the use of pharmacotherapy . This intervention was administered by nurse practitioners . Overall , patients r and omized to naltrexone reported drinking five or more drinks on fewer days than did placebo controls ( p = .04 ) . Interactions were observed between medication group assignment and both craving level prior to r and omization ( p = .02 ) and family loading of alcohol problems ( p = .05 ) . In both cases , the interaction was in the predicted direction . These data suggest that patients with high levels of alcohol craving  or a strong family history of alcoholism are more likely to benefit from naltrexone treatment Acamprosate and naltrexone are effective medications in the treatment of alcoholism . However , effect sizes are modest . Pharmacogenomics may improve patient‐treatment‐matching and effect sizes . It is hypothesized that naltrexone exerts its effect through genetic characteristics associated with the dopaminergic/opioidergic positive reinforcement system , whereas acamprosate works through the glutamatergic/GABAergic negative reinforcement system . Alcohol‐dependent subjects were r and omly assigned to either acamprosate or naltrexone . Subjects participated in a cue‐exposure experiment at the day before and at the last day of medication . Reductions in cue‐induced craving and physiological cue reactivity were measured . Differential effects of naltrexone and acamprosate on these outcomes were tested for different polymorphisms of the opioid , dopamine , glutamate and GABA‐receptors . Significant matching effects were found for polymorphisms at the DRD2 , GABRA6 and GABRB2 gene . In addition , a trend was found for the OPRM1 polymorphism . This provides evidence for the matching potential of genotypes . It is expected that more effective treatments can be offered when genetic information is used in patient‐treatment‐matching CONTEXT Clinical trials have suggested a modest effect of naltrexone as a pharmacotherapy for alcoholism , and a recent study has suggested that the effects may be moderated by variations in the mu-opioid receptor gene ( OPRM1 ) . However , the mechanism by which naltrexone may be differentially effective as a function of the OPRM1 genotype is unclear . OBJECTIVES ( 1 ) To replicate and exp and on the association between the A118 G single nucleotide polymorphism(SNP ) of the OPRM1 gene and alcohol sensitivity , ( 2 ) to examine the effects of naltrexone on alcohol sensitivity , and ( 3 ) to test the A118 G SNP of the OPRM1 gene as a moderator 
    Output:
    
Our results support the fact that the G allele of A118 G polymorphism of OPRM1 moderates the effect of naltrexone  in patients with alcohol dependence .
This genetic marker may therefore identify a subgroup of individuals more likely to respond to this treatment