human
***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: AIMS A multi-centre , r and omized , double-blind , placebo-controlled trial was conducted to evaluate the efficacy and the safety of acamprosate over 8 weeks in Korean alcohol-dependent patients . METHODS One hundred and forty-two alcohol-dependent patients in 12 centres were r and omized to 8 weeks treatment with either acamprosate ( n = 72 ) or a placebo ( n = 70 ) in combination with out-patient psychosocial intervention .  They were predominantly male ( 95.8 % ) , with a mean age of 44.3 + /- 8.3 years ; 76.1 % were married ; 59.9 % were employed ; 58.5 % had received previous alcoholism treatment ( previous mean number of admissions in alcoholism in-patient programmes 4.6 + /- 6.9 ) . At visits to the clinic ( weekly for 4 weeks , then biweekly for 4 weeks ) , a record was made of alcohol use ( Time-Line Follow-Back ) , alcohol craving using a Korean version of the Obsessive Compulsive Drinking Scale and a visual analogue scale , and adverse events . Serum aspartate aminotransferase , alanine aminotransferase , gamma-glutamyltransferase ( GGT ) , blood urea nitrogen and creatinine levels were measured on weeks 0 , 2 , 4 and 8 . RESULTS In the acamprosate group ( A ) , 71.4 % had had alcohol within the 2 days prior to starting medication , against 65.2 % of patients in the placebo group ( P ) ; ( P > 0.05 ) . One hundred and one subjects ( 71.1 % ) completed 8-weeks of treatment ( A , 73.6 % ; P , 68.6 % ; P > 0.05 ) . During the 8-week treatment period , 37 , ( A ) ( n = 72 ) and 32 % ( P ) ( n = 70 ) achieved continuous abstinence ( P > 0.05 ) , and 40 , ( A ) and 39 % ( P ) remained without relapse ( P > 0.05 ) ( defined as a day when a man consumed five or more drinks or a woman four or more drinks ) . The percentage of days abstinent during the 8-week treatment period was 81.2 , ( A ) and 78.5 % ( P ) ( P > 0.05 ) , and the percentage of days without heavy drinking 86.1 ( A ) and 84.9 % ( P ) ( P > 0.05 ) . The mean amount drunk per drinking occasion was 7.2 , ( A ) and 8.6 st and ard drinks ( P ) ( P > 0.05 ) . No statistically significant differences in changes in the serum GGT level or craving scores from baseline to the end-point of treatment were found between the two groups . Recency of drinking prior to commencing study drug predicted percentage of days abstinent in the first 2 weeks on treatment ; however , when ANOVAs were conducted using treatment outcomes as a dependent variable , medication condition as an independent variable and the period of abstinence prior to treatment as a covariate , a significant effect of medication condition was still not seen . CONCLUSIONS Acamprosate was ineffective in reducing drinking  in this Korean sample . The result differs from that of most European acamprosate trials . This might be explained by our sample 's relatively severe alcohol dependence , and low social support , or the fact that many patients were still drinking near to their first medication . The variability of the psychosocial support , ethnicity ( which might also affect acamprosate pharmacokinetics ) and the Korean drinking style , which differs from that of Europeans , might have contributed to our negative result 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 The objective of this study was to compare acamprosate with placebo in the treatment of alcohol-dependent patients during a 6-month post-detoxification treatment and a 3-month medication-free follow-up . Patients ( n = 330 ) were detoxified and r and omized to treatment with acamprosate ( 1998 mg/day ) or placebo within an out-patient programme including medical counselling , psychotherapy and self-help groups . The main outcome criterion was drinking behaviour as assessed by : abstinence/relapse ratio , cumulative abstinence duration ( CAD ) and the period of continued abstinence . Anxiety , depression and craving were also monitored . Intention to treat ( ITT ) statistical principles were followed . Twenty-five per cent of patients dropped out over the first 6 months . At the end of the treatment period , the abstinence rate was 57.9 % for acamprosate and 45.2 % for placebo ( P = 0.03 ) . The CAD was 110+/-77 days for acamprosate and 89+/-77 days for placebo ( P = 0.016 ) . Patients on acamprosate had a higher continuous abstinence rate and experienced less severe relapses . No differential effect was noted for anxiety , depression or craving . Treatment remained positive , but not significant , 3 months after termination of study medication . No significant difference in adverse events was noted between treatment groups . Acamprosate treatment over 180 days was consistently more effective than placebo to maintain abstinence and to diminish relapse severity RATIONALE Little is known about the effect of disulfiram on subjective and autonomic nervous system cue reactivity in the laboratory . The dissuasive psychological effect manifested as a threat would seem to prevail over the pharmacological effect . OBJECTIVES The primary objective was to determine whether there was a difference in cue reactivity responses during a threat condition compared to a neutral condition during alcohol cue exposure . METHODS In a crossover r and omized study , participants received threat and neutral messages during two cue exposure sessions . The threat condition consisted of leading the patients to believe they had ingested 500 mg of disulfiram and the neutral condition of informing them that they had ingested a placebo , while in both condition they received the same placebo . RESULTS Physiological cue reactivity was demonstrated by a decrease in diastolic blood pressure during the threat compared to the neutral condition ( p=0.04 ) . Heart rate and subjective cue reactivity measures remained unchanged . There was a negative affect ( assessed by the Positive and Negative Affect Scale ) by condition by exposure interaction . CONCLUSIONS The threat of a disulfiram-ethanol reaction appears to affect cue reactivity physiologically rather than subjectively . While the data does not show changes in subjective ratings , it is possible that there are alternative beneficial effects arising from other cognitive processes that are not captivated by self-reported craving scales , reflected by decreases in negative affect and blood pressure . From this perspective , disulfiram might be recast to be more acceptable to patients AIMS To evaluate the efficacy of acamprosate in maintaining abstinence in weaned alcohol-dependent patients . DESIGN A multicentre , double-blind , r and omized control trial . Patients were individually r and omly allocated to active or placebo conditions . Abstinence was assessed during a 6-month treatment period and after a 6-month follow-up period . SETTING A community-based , outpatient alcohol rehabilitation programme . PARTICIPANTS Two hundred and forty-six alcohol-dependent patients between the ages of 18 and 65 years were recruited immediately following acute , inpatient withdrawal treatment . MEASUREMENTS The primary outcome measure was self-reported abstinence from alcohol since the previous sessions at 3 , 6 , 9 and 12 months following the start of treatment , with treatment taking place for a period of 6 months . FINDINGS A significantly higher proportion of patients in the acamprosate group were abstinent after 3 months and 6 months of treatment . The percentage of patients with continuous abstinence at the end of the treatment period was almost double for the acamprosate group than for the placebo group ( 40.7 % vs. 20.8 % , respectively ) . Acamprosate significantly increased the retention of patients in the treatment programme . Six months after drug treatment ceased , the criterion of abstinence since the previous visit was reached by significantly more patients from the acamprosate group ( 43.4 % ) than from the placebo group ( 29.8 % ) , but this difference was not statistically significant at the 3-month point after cessation of study medication . CONCLUSIONS Acamprosate may be a useful pharmacological compound for the long-term treatment of alcohol-dependence when applied in a community-based rehabilitation programme 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 Thirty male alcoholic in patients received in a r and om double-blind design placebo ( P ) or disulfiram 250 mg . ( D ) at bedtime in order to evaluate the effects of the latter on EEG-EOG sleep patterns .  Subjects ( S 's ) had no major medical illness and required no medication for 3 weeks prior to the study . There were 13 disulfiram S 's and 17 placebo S 's . The total REM time decreased significantly ( p less than 0.05 ) in the D group . Total number of REM episodes decreased and latency to stage 1 REM increased in the disulfiram group . These results are characteristic of sleep patterns induced by the administration of catecholaminergics and opposite to those induced by catecholamine inhibiting agents 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 
    Output:
    
agent
The only study available on disulfiram showed reduced REM sleep .
Acamprosate showed no/little effect on self-reported sleep but improved sleep continuity and architecture measured by polysomnography .
The two opioidergic drugs naltrexone and nalmefene had mainly detrimental effect on sleep , giving increased insomnia and /or somnolence compared with placebo , although not always significant .
The meta- analysis confirmed significantly increased somnolence and insomnia in the naltrexone group , compared with the placebo .
Overall , the currently available evidence s show more sleep problems with the opioidergic drugs ( especially naltrexone ) , while acamprosate seems to be well tolerated or even beneficial .
Acamprosate might be a more suitable choice when patients with AUD report sleep problems .
***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: AIMS A multi-centre , r and omized , double-blind , placebo-controlled trial was conducted to evaluate the efficacy and the safety of acamprosate over 8 weeks in Korean alcohol-dependent patients . METHODS One hundred and forty-two alcohol-dependent patients in 12 centres were r and omized to 8 weeks treatment with either acamprosate ( n = 72 ) or a placebo ( n = 70 ) in combination with out-patient psychosocial intervention .  They were predominantly male ( 95.8 % ) , with a mean age of 44.3 + /- 8.3 years ; 76.1 % were married ; 59.9 % were employed ; 58.5 % had received previous alcoholism treatment ( previous mean number of admissions in alcoholism in-patient programmes 4.6 + /- 6.9 ) . At visits to the clinic ( weekly for 4 weeks , then biweekly for 4 weeks ) , a record was made of alcohol use ( Time-Line Follow-Back ) , alcohol craving using a Korean version of the Obsessive Compulsive Drinking Scale and a visual analogue scale , and adverse events . Serum aspartate aminotransferase , alanine aminotransferase , gamma-glutamyltransferase ( GGT ) , blood urea nitrogen and creatinine levels were measured on weeks 0 , 2 , 4 and 8 . RESULTS In the acamprosate group ( A ) , 71.4 % had had alcohol within the 2 days prior to starting medication , against 65.2 % of patients in the placebo group ( P ) ; ( P > 0.05 ) . One hundred and one subjects ( 71.1 % ) completed 8-weeks of treatment ( A , 73.6 % ; P , 68.6 % ; P > 0.05 ) . During the 8-week treatment period , 37 , ( A ) ( n = 72 ) and 32 % ( P ) ( n = 70 ) achieved continuous abstinence ( P > 0.05 ) , and 40 , ( A ) and 39 % ( P ) remained without relapse ( P > 0.05 ) ( defined as a day when a man consumed five or more drinks or a woman four or more drinks ) . The percentage of days abstinent during the 8-week treatment period was 81.2 , ( A ) and 78.5 % ( P ) ( P > 0.05 ) , and the percentage of days without heavy drinking 86.1 ( A ) and 84.9 % ( P ) ( P > 0.05 ) . The mean amount drunk per drinking occasion was 7.2 , ( A ) and 8.6 st and ard drinks ( P ) ( P > 0.05 ) . No statistically significant differences in changes in the serum GGT level or craving scores from baseline to the end-point of treatment were found between the two groups . Recency of drinking prior to commencing study drug predicted percentage of days abstinent in the first 2 weeks on treatment ; however , when ANOVAs were conducted using treatment outcomes as a dependent variable , medication condition as an independent variable and the period of abstinence prior to treatment as a covariate , a significant effect of medication condition was still not seen . CONCLUSIONS Acamprosate was ineffective in reducing drinking  in this Korean sample . The result differs from that of most European acamprosate trials . This might be explained by our sample 's relatively severe alcohol dependence , and low social support , or the fact that many patients were still drinking near to their first medication . The variability of the psychosocial support , ethnicity ( which might also affect acamprosate pharmacokinetics ) and the Korean drinking style , which differs from that of Europeans , might have contributed to our negative result 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 The objective of this study was to compare acamprosate with placebo in the treatment of alcohol-dependent patients during a 6-month post-detoxification treatment and a 3-month medication-free follow-up . Patients ( n = 330 ) were detoxified and r and omized to treatment with acamprosate ( 1998 mg/day ) or placebo within an out-patient programme including medical counselling , psychotherapy and self-help groups . The main outcome criterion was drinking behaviour as assessed by : abstinence/relapse ratio , cumulative abstinence duration ( CAD ) and the period of continued abstinence . Anxiety , depression and craving were also monitored . Intention to treat ( ITT ) statistical principles were followed . Twenty-five per cent of patients dropped out over the first 6 months . At the end of the treatment period , the abstinence rate was 57.9 % for acamprosate and 45.2 % for placebo ( P = 0.03 ) . The CAD was 110+/-77 days for acamprosate and 89+/-77 days for placebo ( P = 0.016 ) . Patients on acamprosate had a higher continuous abstinence rate and experienced less severe relapses . No differential effect was noted for anxiety , depression or craving . Treatment remained positive , but not significant , 3 months after termination of study medication . No significant difference in adverse events was noted between treatment groups . Acamprosate treatment over 180 days was consistently more effective than placebo to maintain abstinence and to diminish relapse severity RATIONALE Little is known about the effect of disulfiram on subjective and autonomic nervous system cue reactivity in the laboratory . The dissuasive psychological effect manifested as a threat would seem to prevail over the pharmacological effect . OBJECTIVES The primary objective was to determine whether there was a difference in cue reactivity responses during a threat condition compared to a neutral condition during alcohol cue exposure . METHODS In a crossover r and omized study , participants received threat and neutral messages during two cue exposure sessions . The threat condition consisted of leading the patients to believe they had ingested 500 mg of disulfiram and the neutral condition of informing them that they had ingested a placebo , while in both condition they received the same placebo . RESULTS Physiological cue reactivity was demonstrated by a decrease in diastolic blood pressure during the threat compared to the neutral condition ( p=0.04 ) . Heart rate and subjective cue reactivity measures remained unchanged . There was a negative affect ( assessed by the Positive and Negative Affect Scale ) by condition by exposure interaction . CONCLUSIONS The threat of a disulfiram-ethanol reaction appears to affect cue reactivity physiologically rather than subjectively . While the data does not show changes in subjective ratings , it is possible that there are alternative beneficial effects arising from other cognitive processes that are not captivated by self-reported craving scales , reflected by decreases in negative affect and blood pressure . From this perspective , disulfiram might be recast to be more acceptable to patients AIMS To evaluate the efficacy of acamprosate in maintaining abstinence in weaned alcohol-dependent patients . DESIGN A multicentre , double-blind , r and omized control trial . Patients were individually r and omly allocated to active or placebo conditions . Abstinence was assessed during a 6-month treatment period and after a 6-month follow-up period . SETTING A community-based , outpatient alcohol rehabilitation programme . PARTICIPANTS Two hundred and forty-six alcohol-dependent patients between the ages of 18 and 65 years were recruited immediately following acute , inpatient withdrawal treatment . MEASUREMENTS The primary outcome measure was self-reported abstinence from alcohol since the previous sessions at 3 , 6 , 9 and 12 months following the start of treatment , with treatment taking place for a period of 6 months . FINDINGS A significantly higher proportion of patients in the acamprosate group were abstinent after 3 months and 6 months of treatment . The percentage of patients with continuous abstinence at the end of the treatment period was almost double for the acamprosate group than for the placebo group ( 40.7 % vs. 20.8 % , respectively ) . Acamprosate significantly increased the retention of patients in the treatment programme . Six months after drug treatment ceased , the criterion of abstinence since the previous visit was reached by significantly more patients from the acamprosate group ( 43.4 % ) than from the placebo group ( 29.8 % ) , but this difference was not statistically significant at the 3-month point after cessation of study medication . CONCLUSIONS Acamprosate may be a useful pharmacological compound for the long-term treatment of alcohol-dependence when applied in a community-based rehabilitation programme 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 Thirty male alcoholic in patients received in a r and om double-blind design placebo ( P ) or disulfiram 250 mg . ( D ) at bedtime in order to evaluate the effects of the latter on EEG-EOG sleep patterns .  Subjects ( S 's ) had no major medical illness and required no medication for 3 weeks prior to the study . There were 13 disulfiram S 's and 17 placebo S 's . The total REM time decreased significantly ( p less than 0.05 ) in the D group . Total number of REM episodes decreased and latency to stage 1 REM increased in the disulfiram group . These results are characteristic of sleep patterns induced by the administration of catecholaminergics and opposite to those induced by catecholamine inhibiting agents 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 
    Output:
    