title: Acamprosate in Korean alcohol-dependent patients: a multi-centre, randomized, double-blind, placebo-controlled study. Naltrexone vs. Nefazodone for Treatment of Alcohol Dependence: A Placebo-Controlled Trial Acamprosate and relapse prevention in the treatment of alcohol dependence: a placebo-controlled study. Effect of the threat of a disulfiram-ethanol reaction on cue reactivity in alcoholics. Acamprosate treatment in a long-term community-based alcohol rehabilitation programme. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. Effects of disulfiram on the sleep of chronic alcoholics. 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. Acute intravenous administration of morphine perturbs sleep architecture in healthy pain-free young adults: a preliminary study. Targeted Naltrexone for Early Problem Drinkers Efficacy of As-Needed Nalmefene in Alcohol-Dependent Patients with at Least a High Drinking Risk Level: Results from a Subgroup Analysis of Two Randomized Controlled 6-Month Studies A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Naltrexone as an adjunctive treatment for older patients with alcohol dependence. A placebo-controlled randomized clinical trial of naltrexone in the context of different levels of psychosocial intervention. Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study. Comparison of acamprosate and placebo in long-term treatment of alcohol dependence Lack of Efficacy of Naltrexone in the Prevention of Alcohol Relapse: Results From a German Multicenter Study Sleep disturbance and risk for alcohol-related problems. Morphine effects on human REM state, waking state and NREM sleep Naltrexone for alcohol-dependent patients Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependent patients. A 90-day placebo-controlled dose-finding study. Pharmacodynamic Effects of Acamprosate on Markers of Cerebral Function in Alcohol-Dependent Subjects Administered as Pretreatment and during Alcohol Abstinence Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study. Sleep Laboratory Study on Single and Repeated Dose Effects of Paroxetine, Alprazolam and Their Combination in Healthy Young Volunteers A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence. Comparing topiramate with naltrexone in the treatment of alcohol dependence. Sleep disturbance in alcoholism: proposal of a simple measurement, and results from a 24-week randomized controlled study of alcohol-dependent patients assessing acamprosate efficacy. [Acamprosate--a stabilizing factor in long-term withdrawal of alcoholic patients]. Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: results of a placebo-controlled trial. Extending the Treatment Options in Alcohol Dependence: A Randomized Controlled Study of As-Needed Nalmefene Targeted Use of Naltrexone Without Prior Detoxification in the Treatment of Alcohol Dependence: A Factorial Double-Blind, Placebo-Controlled Trial A pilot evaluation of the safety and tolerability of repeat dose administration of long-acting injectable naltrexone (Vivitrex) in patients with alcohol dependence. A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence. Prescribed sedative and other psychotropic medication use among clients attending alcohol and other drug treatment Long-term effects of pharmacotherapy on relapse prevention in alcohol dependence. Effects of naltrexone on adolescent alcohol cue reactivity and sensitivity: an initial randomized trial
abstract: 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 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 STUDY OBJECTIVES Pain is a leading cause of sleep disturbances in medical illness . Providing effective analgesia is considered an important intervention to reduce these sleep disturbances . Opioids remain the treatment of choice to relieve postoperative pain in hospitalized patients . However , their effects on sleep in pain patients or normal subjects remain unclear , as previous studies have been conducted mainly with former opioid addicts . The purpose of this investigation was to evaluate and describe the effects of acute clinical doses of morphine on sleep in healthy pain-free subjects . DESIGN Subjects were r and omly assigned to untreated ( baseline ) , morphine ( intravenous injections of 0.1 [ DOSAGE ERROR CORRECTED ] mg/kg ) , and placebo ( intravenous injections of 0.9 % NaCI ) conditions . SETTING Sleep laboratory . PARTICIPANTS Seven healthy pain-free , nonaddicts ( 5 women , 2 men ; mean age = 25 + /- 1.6 years ) . MEASUREMENTS AND RESULTS St and ard polysomnographic sleep and respiratory variables were measured during 3 experimental conditions . The treatment effect was analyzed with a Latin square cross-over design followed , when appropriate , by Tukey contrasts . Morphine altered sleep architecture by reducing slow-wave sleep ( non-rapid eye movement stages 3 - 4 ) and rapid eye movement sleep , and by increasing non-rapid eye movement stage 2 sleep . Results did not reveal any statistical differences for other sleep and respiratory variables . CONCLUSIONS Similar to earlier findings in animals , nondependent opiate addicts , and postoperative patients , morphine was found to reduce duration of slow-wave sleep . Unlike previous reports , however , its acute administration produced a moderate reduction in rapid eye movement sleep and did not increase correlates of arousal ( ie , awakenings , electroencephalogram arousals , wake after sleep onset ) . Future studies should correlate these findings in patients with pain and evaluate whether optimal pain relief with opioid therapy can improve sleep disturbances in pain patients Most published studies of the efficacy of naltrexone for alcohol treatment have focused on daily medication for relapse prevention among abstinent alcoholics . The present study compared the effects of naltrexone with those of placebo in a sample of early problem drinkers who received study medication either daily or targeted to situations identified by the patients as being high risk for heavy drinking . Patients ( n = 153 ; 58 % male ) were r and omly assigned to receive naltrexone ( 50 mg ) or placebo on a daily or targeted basis , yielding comparable numbers of patients in each of four treatment groups . Patients were trained to use structured nightly diaries in which they recorded their alcohol consumption and medication intake . Analysis was conducted with hierarchical linear modeling . Irrespective of whether they received naltrexone or placebo , patients in the targeted condition showed a reduced likelihood of any drinking . There was a reduced likelihood of heavy drinking , both for patients who received naltrexone and for patients who were in the targeted groups ( either naltrexone or placebo ) , although these effects diminished as the number of tablets available to the targeted groups was reduced over the 8-week treatment period . Although the effect was a modest one , daily naltrexone reduced the risk of heavy drinking in this patient group . Furthermore , use of a targeted approach to medication treatment appears to be a useful strategy for reducing both drinking and heavy drinking . Efforts to replicate these findings are warranted , since they suggest that schedules of medication administration other than daily should be evaluated for treatment of problem drinking Aims : The aim of the study was to investigate the efficacy and safety of as-needed use of nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment , i.e. the pooled subgroup of patients with at least a high drinking risk level ( men : > 60 g/day ; women : > 40 g/day ) at both screening and r and omization from the two r and omized controlled 6-month studies ESENSE 1 ( NCT00811720 ) and ESENSE 2 ( NCT00812461 ) . Methods : Nalmefene 18 mg and placebo were taken on an as-needed basis . All the patients also received a motivational and adherence-enhancing intervention ( BRENDA ) . The co- primary outcomes were number of heavy drinking days ( HDDs ) and mean total alcohol consumption ( g/day ) in Month 6 measured using the Timeline Follow-back method . Additionally , data on clinical improvement , liver function and safety were collected throughout the study . Results : The pooled population consisted of 667 patients : placebo n = 332 ; nalmefene  n = 335 . There was a superior effect of nalmefene compared with placebo in reducing the number of HDDs [ treatment difference : −3.2 days ( 95 % CI : −4.8 ; −1.6 ) ; P < 0.0001 ] and total alcohol consumption [ treatment difference : −14.3 g/day ( −20.8 ; −7.8 ) ; P < 0.0001 ] at Month 6 . Improvements in clinical status and liver parameters were greater in the nalmefene group compared with the placebo group . Adverse events and adverse events leading to dropout were more common with nalmefene than placebo . Conclusion : As-needed nalmefene was efficacious in reducing alcohol consumption in patients with at least a high drinking risk level at both screening and r and omization , and the effect in this subgroup was larger than in the total population The opioid antagonist , naltrexone , is reported , in single centre studies , to improve the clinical outcome of individuals with alcohol dependence participating in outpatient psychosocial programmes . This is the first multicentre controlled study to evaluate the efficacy and safety of naltrexone as adjunctive treatment for alcohol dependence or abuse . Patients who met criteria for alcohol dependence ( n = 169 ) or alcohol abuse ( n = 6 ) were r and omly assigned to receive double-blind oral naltrexone 50 mg daily ( n = 90 ) or placebo ( n = 85 ) for 12 weeks as an adjunct to psychosocial treatment . The primary efficacy variable was time to first episode of heavy drinking ; secondary efficacy assessment s included time to first drink , alcohol consumption , craving , and changes in the serum biological markers gamma-glutamyl transferase ( GGT ) , and aspartate and alanine aminotransferases . Compliance was assessed by tablet counts and , in the naltrexone-treated group , by measurement of urinary concentrations of 6-ss-naltrexol . Forty-nine ( 58 % ) patients r and omized to placebo and 53 ( 59 % ) r and omized to naltrexone  did not complete the study . In intention-to-treat analyses , there was no difference between groups on measures of drinking . The median reduction from baseline of serum GGT ( P : < 0.05 ) and the reductions in alcohol craving ( Obsessive and Compulsive Drinking Scale : OCDS ) were greater in the naltrexone group ( P : < 0.05 ) , from approximately half-way through the study . Of 70 patients ( 35 placebo ; 35 naltrexone ) who met an a priori definition of compliance ( 80 % tablet consumption , attendance at all follow-up appointments ) , those allocated to naltrexone reported consuming half the amount of alcohol ( P : < 0.05 ) , had greater median reduction in serum GGT activity ( P : < 0.05 ) , and greater reduction in alcohol craving ( OCDS total score : P : < 0.05 ; Obsessive subscale score : P : < 0.05 ) , compared to patients in the placebo group . Use of naltrexone raised no safety concerns . Naltrexone is effective in treating alcohol dependence/abuse in conjunction with psychosocial therapy , in patients who comply with treatment The authors examined the efficacy of naltrexone as an adjunctive treatment for alcohol dependence in older adults . Forty-four veterans over 50 years of age were enrolled in a 12-week , double-blind , placebo-controlled efficacy study of naltrexone ( the equivalent of 50 mg per day ) . There were no differences in the frequency of any self-reported adverse effects or in liver enzyme values between the placebo- and naltrexone-treated groups . There were no differences between the treatment groups in the number of subjects remaining abstinent or in the number of subjects who relapsed . However , all placebo-treated subjects relapsed after sampling alcohol , whereas only three of six naltrexone-treated subjects met relapse criteria after alcohol exposure ( P = 0.024 ) . The authors conclude that naltrexone was well tolerated and efficacious in preventing relapse in subjects who drank BACKGROUND Naltrexone is approved for the treatment of alcohol dependence when used in conjunction with a psychosocial intervention . This study was undertaken to examine the impact of 3 types of psychosocial treatment combined with either naltrexone or placebo treatment on alcohol dependency over 24 weeks of treatment : ( 1 ) Cognitive-Behavioral Therapy ( CBT ) + medication clinic , ( 2 ) BRENDA ( an intervention promoting pharmacotherapy ) + medication clinic , and ( 3 ) a medication clinic model with limited therapeutic content . METHODS Two hundred and forty alcohol-dependent subjects were enrolled in a 24-week double-blind placebo-controlled study of naltrexone ( 100 mg/d ) . Subjects were also r and omly assigned to 1 of 3 psychosocial interventions . All patients were assessed for alcohol use , medication adherence , and adverse events at regularly scheduled research visits . RESULTS There was a modest main treatment effect for the psychosocial condition favoring those subjects r and omized to CBT . Intent-to-treat analyses suggested that there was no overall efficacy of naltrexone and no medication by psychosocial intervention interaction . There was a relatively low level of medication adherence ( 50 % adhered ) across conditions , and this was associated with poor outcome . CONCLUSIONS Results from this 24-week treatment study demonstrate the importance of the psychosocial component in the treatment of alcohol dependence . Moreover , results demonstrate a substantial association between medication adherence and treatment outcomes . The findings suggest that further research is needed to determine the appropriate use of pharmacotherapy in maximizing treatment response BACKGROUND Clinical studies with opioid antagonists for treatment of  problem drinking  have mainly been conducted in specialized alcohol treatment centers , included structured psychosocial treatment , and have focused on maintaining abstinence after a period of abstinence from alcohol . METHODS This multisite , r and omized double-blind study investigated targeted nalmefene in reducing heavy drinking . Specialized alcohol treatment centers and private general practice s enrolled 403 subjects ( 328 men , 75 women ) . Subjects were instructed to take nalmefene 10 to 40 mg ( n=242 ) or placebo ( n=161 ) when they believed drinking to be imminent . After 28 weeks , 57 subjects from the nalmefene group continued into a 24-week r and omized withdrawal extension . Concomitant psychosocial intervention was minimal and no treatment goals were imposed . Alcohol consumption was recorded using the time-line follow-back method . Biochemical indicators of alcohol use were also measured . RESULTS The mean monthly number of heavy drinking days ( HDDs ) during the 12-week period before inclusion was 15.5 ( SD 6.9 ) in the nalmefene group and 16.2 ( SD 6.9 ) in the placebo group . During treatment , the mean numbers of HDDs were 8.6 to 9.3 in the nalmefene group and 10.6 to 12.0 in the placebo group ( p=0.0065 ) . The levels of serum alanine aminotransferase and gamma-glutamyl transferase decreased in the nalmefene group compared with the placebo group ( p=0.0088 and 0.0023 ) . During the r and omized withdrawal period , subjects r and omized to placebo apparently returned to heavier drinking . Subjects receiving  nalmefene  reported more nausea , insomnia , fatigue , dizziness , and malaise than subjects on placebo . CONCLUSIONS Nalmefene appears to be effective and safe in reducing heavy drinking , even when accompanied by minimal psychosocial support BACKGROUND About 50 % of alcoholic patients relapse within 3 months of treatment . Previous studies have suggested that acamprosate may help to prevent such relapse . The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence . METHODS In this multicentre , double-blind , placebo-controlled study , we recruited 455 patients , aged 18 - 65 years , with chronic or episodic alcohol dependence . Patients were r and omly allocated treatment with acamprosate ( 1998 mg daily for bodyweight > 60 kg ; 1332 mg daily for < or = kg ) or placebo for 360 days . Patients were assessed on the day treatment started and on days 30 , 90 , 180 , 270 , and 360 by interview , self-report , question naire , and laboratory screening . Patients were classified as abstinent , relapsing , or non-attending . Time to first treatment failure ( relapse or non-attendance ) was the primary outcome measure . FINDINGS Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication . The acamprosate ( n = 224 ) and placebo ( n = 224 ) groups were well matched in terms of baseline demographic and alcohol-related variables . 94 acamprosate-treated  and 85 placebo-treated patients completed the treatment phase : of those withdrawn , 104 ( 52 in each group ) relapsed , 69 ( 33 vs 36 , respectively ) were lost to follow-up , 63 ( 31 vs 32 ) refused to continue treatment , 16 ( 15 vs 11 ) had concurrent illness , three ( two vs one ) died , ten ( six vs four ) had adverse side-effects , one ( acamprosate treated ) received the wrong medication , and three ( placebo treated ) were non-compliant . The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period ( p < 0.001 , Mantel-Cox ) . At the end of treatment , 41 ( 18.3 % ) acamprosate-treated and 16 ( 7.1 % ) placebo-treated patients had been continuously abstinent ( p = 0.007 ) . Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group ( 138.8 [ SD 137.5 ] vs 103.8 [ 119.0 ] days ; p = 0.012 ) . 148 patients ( 79 acamprosate , 69 placebo ) completed 27 months follow-up : 27 ( 11.9 % ) acamprosate-treated and 11 ( 4.9 % ) placebo-treated patients remained continuously abstinent , and the mean cumulative abstinence duration was 230.8 days ( 259.1 ) and 183.0 days ( 235.2 ) , respectively . Apart from occasional diarrhoea , there was no difference in side-effects between groups . INTERPRETATION Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients In a placebo-controlled , double-blind German multicenter study ( seven sites ) the efficacy of naltrexone as an adjunctive treatment in alcoholism to maintain abstinence was assessed for 12 weeks . A total of 171 detoxified patients ( 97.7 % met the DSM-III-R criteria for alcohol dependence ) were included . Patients had been abstinent for a mean of 19.5 ± 9.4 days at study entry . Eighty-four and 87 patients were r and omized to receive naltrexone  ( 50 mg/day ) and placebo , respectively . Each site was instructed to provide its usual psychosocial alcohol treatment program . The primary effectiveness measure was the time to first heavy drinking as derived from self-reports of drinking ( timeline-follow-back method ) . Secondary effectiveness measures included time to first drink , amount of alcohol consumption , intensity of craving , severity of alcoholism problems , and liver enzymes . Thirty-three ( 38 % ) placebo patients and 28 ( 33 % ) naltrexone patients discontinued the study . At endpoint , 62 % of the patients in each group did not have an episode of heavy drinking . Also , there were no significant differences between the study groups concerning secondary effectiveness measures as well as compliance and adverse clinical events — with the exception of the γ-GT , which was significantly greater reduced in the naltrexone group throughout the study . Based upon an intention-to-treat population , this study confirms the safety but not the efficacy of naltrexone in prevention of alcohol relapse . Nevertheless , the question arises whether self-reports of drinking are more reliable than γ-GT as a measure of recent alcohol consumption OBJECTIVE Using prospect i ve data , the authors assessed the risk of alcohol-related problems among individuals with self-reported sleep disturbances because of worry . METHOD As part of the Epidemiologic Catchment Area program , a probability sample of Baltimore residents selected by census tracts and households completed a baseline interview in 1981 . Between 1993 and 1996 , the original Baltimore cohort was traced . Of the 2,633 survivors , a total of 73 % were reinterviewed . After excluding individuals with alcohol-related problems or a current or prior history of alcohol abuse and /or dependence at the time of the 1981 interview , the authors identified a cohort of 1,537 individuals who were at risk for problem drinking at the time of the follow-up interview , a median of 12.6 years after the baseline interview .  Logistic regression was used to assess the association between sleep disturbance because of worry and the risk for incident reports of alcohol problems . RESULTS Survey respondents with sleep disturbances because of worry  at the time of the baseline interview had a twofold higher risk for developing an alcohol-related problem , relative to those without these sleep disturbances ( odds ratio=2.32 , 95 % confidence interval [CI]=1.31 - 4.09 ) , with adjustment for selected demographic and clinical variables . Sleep disturbance because of worry predicted the development of alcohol problems among respondents with lifetime anxiety disorders and lifetime dysphoria ( odds ratio=3.82 , 95 % CI=1.56 - 9.38 , and odds ratio=2.71 , 95 % CI=1.25 - 5.91 , respectively ) , but not among those without a history of anxiety disorders or dysphoria . CONCLUSIONS Sleep disturbances because of worry may increase risk for alcohol-related problems . Risk is highest for those with sleep disturbance and co-occurring anxiety disorders or dysphoria Summary After 4 adaptation nights , IM doses of morphine sulfate ( 7.5 , 15 , 30 mg/70 kg ) and placebo were studied in 8 male postaddicts , using a cross-over design with r and omized block analysis to demonstrate significant drug effect . Morphine decreased the number and duration of REM periods , delayed the onset of the first REM period , and possibly increased the time between REM period onsets . Thus , morphine significantly decreased REM state ( REMS ) , but did not alter the pattern of maximum REMS in late night . Morphine significantly increased waking state ( WS ) but did not alter the pattern of maximum WS in early night . Morphine significantly increased tension , and shifted maximum tension from early night to middle night . Morphine altered EEG sleep patterns ; although NREM definitions were thus less certain , morphine appeared to increase NREM light sleep ( stages 1 and 2 ) and decrease NREM deep sleep ( stages 3 and 4 ) . After an initial decrease in REMS by 30 mg/70 kg of morphine , an increase in REMS was noted in the third night of the 2 pilot study subjects . The arousal response to morphine seen in post-addicts needs further study in other population s and during the course of chronic morphine use Background Clinical trials have shown that naltrexone 50mg/day reduces alcohol consumption and relapse rates in alcohol dependents . Aim To investigate the efficacy of 50mg/day dose of naltrexone in the maintenance of alcohol-dependent subjects over a 36-week treatment period . Methods Subjects were r and omised into two equal groups , consisting of 116 male alcohol-dependent patients who met the DSM-IV criteria for alcohol dependence and were seeking treatment . The participants received naltrexone or placebo at a dose of 50mg/day and were treated in an outpatient clinic , offering a weekly 0.5-hour individual counselling session . Days retained in treatment were measured . Results Forty-one participants ( 35.3 % ) completed the 36-week study . Completion rates by group were 44.8 % for the 50 mg naltrexone group and 25.9 % for the placebo group ( x2=4.56 , DF=1 , 2-sided significance = 0.033 ) . Conclusion The results support the efficacy and safety of naltrexone for outpatient treatment of alcohol-dependent individuals in Iran BACKGROUND Acamprosate is a newly registered drug that appears to reduce  alcohol-drinking  in both animal models and clinical conditions . METHOD In order to assess the efficacy and safety of the drug in the treatment of detoxified alcoholics , we performed a 90-day double-blind trial comparing two dosages of acamprosate ( 1332 mg/day and 1998 mg/day ) . RESULTS For all efficacy parameters , acamprosate appeared to be significantly superior to placebo , with a trend towards a better effect at the higher dosage . Furthermore , acamprosate appeared to be extremely safe . CONCLUSION This study confirms that acamprosate could be an interesting adjuvant for maintaining abstinence in detoxified alcoholics Animal studies suggested that acamprosate modulates neuronal hyperexcitability of acute alcohol withdrawal , acting through the glutamatergic neurotransmission . In the present study , we further investigated whether treatment with acamprosate could attenuate the post-alcohol withdrawal hyperexcitability or hyperarousal in humans using brain magnetoencephalography mapping of spontaneous fields . A double-blind , r and omised , placebo-controlled study with a parallel group design comparing 2,000 mg/day of acamprosate versus placebo was conducted in alcohol-dependent subjects meeting DSM-IV criteria for alcohol dependence . Treatments were initiated 8 days before alcohol withdrawal and prolonged during the 15 following ( abstinence ) days . The study demonstrated that during alcohol withdrawal , acamprosate decreased the arousal level as reflected by alpha slow-wave index ( ASI ) measurement . This effect was mostly evidence d in left parietotemporal regions and , to a lesser extent , in the contiguous anterior , posterior and right-sided regions . In the placebo group , on the contrary , ASI measures increased between day 2 ( acute withdrawal ) and day 14 ( prolonged withdrawal ) . The present results suggest a sustained effect of acamprosate on the hyperexcitability state due to alcohol withdrawal in alcohol-dependent patients and that acamprosate may have a protective effect when administered 8 days before alcohol withdrawal This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence . One hundred eighteen patients were r and omly assigned to either placebo or acamprosate , and both groups were stratified for concomitant voluntary use of disulfiram . Treatment lasted for 360 days , with an additional 360-day follow-up period . The primary efficacy parameters evaluated were : relapse rate and cumulative abstinence duration ( CAD ) . Results were analyzed according to Intention-To-Treat principles using chi2 , t , and multiple regression analyses where appropriate . After 30 days on study medication , 40 of 55 ( 73 % ) acamprosate-treated patients were abstinent , compared with 26 of 55 ( 43 % ) placebo-treated patients ( p = 0.019 ) . The treatment advantage remained throughout the study medication period and was statistically significant until day 270 ( p = 0.028 ) . Twenty-seven percent of patients on acamprosate and 53 % of patients on placebo had a first drink within the first 30 days of the study . The mean CAD was 137 days ( 40 % abstinent days ) for the patients treated with acamprosate and 75 days ( 21 % abstinent days ) for the placebo group ( p = 0.013 ) . No adverse interaction between acamprosate and disulfiram occurred , and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication . Acamprosate was well tolerated . Diarrhea was the only significant treatment-induced effect . It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism . Concomitant administration of disulfiram improved the effectiveness of acamprosate Aims : To evaluate the potential interaction of 20 mg paroxetine and 1 mg alprazolam ( early morning once-daily administration ) on polysomnographic ( PSG ) sleep and subjective sleep and awakening quality , both after a single intake and after reaching a steady-state concentration . Methods : Twenty-two ( 11 for the PSG ) healthy young volunteers of both sexes with no history of sleep disturbances ( Pittsburgh Sleep Quality Index < 5 ) participated in a double-blind , double-dummy , placebo-controlled , repeated-dose , 4-period , cross-over study . All volunteers received all 4 treatment sequences : paroxetine – alprazolam placebo ( PAP ) ; paroxetine placebo – alprazolam ( PPA ) ; paroxetine – alprazolam ( PA ) , and paroxetine placebo – alprazolam placebo ( PLA ) , in a r and omized order . Each treatment was administered over 15 consecutive days , with a treatment-free interval of 7 days prior to the subsequent study period . In each experimental period , one PSG sleep study was performed on the 1st night ( single-dose effects ) and another study was performed on the 15th night ( repeated-dose effects ) . Additionally , two other PSG studies were assessed : an adaptation recording , and a control night recording . All-night PSG recordings were obtained following st and ard procedures . Each 30-second period was scored according to the criteria of Rechtschaffen and Kales by means of an automatic sleep analysis system : Somnolyzer 24x7TM . A self-rating scale for sleep and awakening quality and early morning behavior was completed no later than 15 min after awakening over the 15 days of each experimental intervention . General lineal models ( treatment/time ) were applied separately to each variable . Results : ( 1 ) No significant effects were observed in any sleep variables when control nights were compared with the 1st night with PLA . ( 2 ) Sleep continuity : After PAP a clear awakening effect was seen both in the first and second evaluations , mainly in wake time , movement time , number of awakenings and stage-1 duration . After PPA an evident hypnotic effect was observed on night 1 . This effect was mainly observed in maintenance variables and slightly in sleep initiation variables ; it had decreased by night 15 . After PA an intermediate behavior in the variables related to sleep continuity was seen , highlighting the absence of the tolerance phenomenon observed when PPA was administered alone . ( 3 ) Sleep architecture : The most important effects in REM sleep were observed after PAP ; an increase in REM latency and decreases in REM sleep .  PAP also induced decreases in the number of non-REM and REM periods and increases in the average duration of non-REM periods and sleep cycles . PA presented a similar pattern to PAP , and PPA similar to PLA . In relation to non-REM sleep , PA showed more stage-2 and less slow-wave sleep ( SWS ) . ( 4 ) Subjective perception : No significant differences were observed between treatments while they were being taken , but impairments in subjective sleep quality , awaking quality , latency and efficiency were seen , mainly after PA but also after PPA discontinuations . Conclusion : The combination of PAP and PPA presented an intermediate pattern in relation to sleep continuity , with less awaking effect than PAP alone and less hypnotic effect than PPA alone , and without developing tolerance . The PAP and PPA combination also showed a similar effect to PAP on REM sleep and was the treatment with the longest stage 2 and shortest SWS . No subjective sleep and awakening effects were seen during drug intake but subjective withdrawal reports were seen after abrupt interruption . The high agreement rate for the epoch-by-epoch comparison between automatic and human scoring confirms the validity of the Somnolyzer 24x7 and thus facilitates sleep studies in neuropsychopharmacological research BACKGROUND Nalmefene is a newer opioid antagonist that is structurally similar to naltrexone but with a number of potential pharmacological advantages for the treatment of alcohol dependence , including no dose-dependent association with toxic effects to the liver , greater oral bioavailability , longer duration of antagonist action , and more competitive binding with opioid receptor subtypes that are thought to reinforce drinking . METHODS A double-blind , placebo-controlled trial was conducted to evaluate the safety and efficacy of 2 doses of oral nalmefene for alcohol dependence . The 105 outpatient volunteers were abstinent for a mean of 2 weeks prior to r and om assignment to the placebo or 20- or 80-mg/d dose nalmefene groups for 12 weeks . Cognitive behavioral therapy was provided weekly during treatment . Self-reported drinking or abstinence was confirmed by determinations of breath alcohol concentration and by collateral informant reports . RESULTS Outcomes did not differ between the 20- and 80-mg dose nalmefene groups . Significantly fewer patients treated with nalmefene than patients given placebo  relapsed to heavy drinking through 12 weeks of treatment ( P<.02 ) , with a significant treatment effect at the first weekly study visit ( P<.02 ) . The odds ratio of relapsing to heavy drinking was 2.4 times greater with placebo compared with nalmefene ( 95 % confidence interval , 1.05 - 5.59 ) . Patients treated with nalmefene also had fewer subsequent relapses ( P<.03 ) than patients given placebo . CONCLUSIONS Treatment with nalmefene was effective in preventing relapse to heavy drinking relative to placebo in alcohol-dependent out patients and was accompanied by acceptable side effects AIM To compare the efficacy of topiramate with naltrexone in the treatment of alcohol dependence . DESIGN The investigation was a double-blind , placebo-controlled , 12-week study carried out at the University of São Paulo , Brazil . SAMPLE A total of 155 patients , 18 - 60 years of age , with an International Classification of Diseases ( ICD-10 ) diagnosis of alcohol dependence . METHODS After a 1-week detoxification period , patients were assigned r and omly to receive topiramate ( induction to 300 mg/day ) , naltrexone ( 50 mg/day ) or placebo . MEASUREMENTS Time to first relapse ( consumption of > 60 g ethyl alcohol ) , cumulative abstinence duration and weeks of heavy drinking . FINDINGS In intention-to-treat analyses , topiramate was statistically superior to placebo on a number of measures including time to first relapse ( 7.8 versus 5.0 weeks ) , cumulative abstinence duration ( 8.2 versus 5.6 weeks ) , weeks of heavy drinking ( 3.4 versus 5.9 ) and percentage of subjects abstinent at 4 weeks ( 67.3 versus 42.6 ) and 8 weeks ( 61.5 versus 31.5 ) , but not 12 weeks ( 46.2 versus 27.8 ) . RESULTS remained significant after controlling for Alcoholics Anonymous attendance , which was higher in topiramate than in other groups . There were no significant differences between naltrexone versus placebo or naltrexone versus topiramate groups , but naltrexone showed trends toward inferior outcomes when compared to topiramate . CONCLUSIONS The results of this study support the efficacy of topiramate in the relapse prevention of alcoholism . Suggestive evidence was also obtained for superiority of topiramate versus naltrexone , but this needs to be verified in future research with larger sample sizes AIMS Sleep disturbance symptom ( SDS ) is commonly reported in alcoholic patients . Polysomnography studies suggested that acamprosate decreased SDS . We assessed this hypothesis by using data of a r and omized controlled trial . As a secondary objective , we suggested and tested the validity of a simple measurement of SDS based on the Hamilton depression and anxiety inventory subset . METHODS We re-analysed a multi-center study evaluating the efficacy of acamprosate compared with placebos on alcohol-dependent patients in concentrating on SDS change in time . The Sleep sum score index ( SAEI ) was built from check-lists on adverse effects reported at each visit and constituted our main endpoint . We also tested the validity of the short sleep index ( SSI ) defined by the four sleep items of the Hamilton depression and anxiety scales . Statistical analyses were conducted on an intention to treat basis . RESULTS A total of 592 patients were included , and 292 completed the 6-month trial . Compared with SAEI considered as our reference , the observed specificity and sensitivity of SSI were 91.6 and 87.6 % . From 40.2 % of patients experiencing SDS at baseline , this proportion decreased until 26.1 % at M6 in the placebo group and 19.5 % in the acamprosate group ( relative risk placebo/acamprosate = 1.49 , 95 % confidence interval 1.10 , 1.98 , P = 0.04 ) . CONCLUSION Treating alcoholic patients to enhance abstinence has a beneficial effect in reducing SDS , and the duration of abstinence during the treatment constitutes the main positive factor . An additional effect of acamprosate is conjectured from its effect on the glutamatergic tone . The SSI constitutes a simple , reasonably sensitive and specific instrument tool to measure SDS In a one-year double-blind-treatment study with acamprosat ( six months with and six months without substance ) the efficiency of this new medicament could be proved . The number of relapses in the treatment group was significantly lower during the first 30 days with a trend to further 150 days . The substance caused very few side effects OBJECTIVE The opiate antagonist drug naltrexone has been shown in a few studies with limited sample sizes to be effective when combined with psychosocial therapies for the treatment of alcohol dependence . The goal of this study was to obtain additional information regarding its efficacy in pertinent alcoholic population s and with a well-defined therapy . METHOD In this study , 131 recently abstinent alcohol-dependent out patients were treated with 12 weekly sessions of manual-guided cognitive behavioral therapy and either 50 mg/day of naltrexone ( N = 68 ) or placebo ( N = 63 ) ( with riboflavin added as a marker of compliance ) in a double-blind , r and omized clinical trial . Alcohol consumption , craving , adverse events , and urinary riboflavin levels were assessed weekly . Levels of blood markers of alcohol abuse were also ascertained during the trial . RESULTS The study completion , therapy participation , and medication compliance rates in the trial were high , with no differences between treatment groups . Naltrexone-treated subjects drank less , took longer to relapse , and had more time between relapses . They also exhibited more resistance to and control over alcohol-related thoughts and urges , as measured by a subscale of the Obsessive Compulsive Drinking Scale . Over the study period , 62 % of the naltrexone group did not relapse into heavy drinking , in comparison with 40 % of the placebo group . CONCLUSIONS Motivated individuals with moderate alcohol dependence can be treated with greater effectiveness when naltrexone is used in conjunction with weekly outpatient cognitive behavioral therapy . Naltrexone increases control over alcohol urges and improves cognitive resistance to thoughts about drinking . Thus , the therapeutic effects of cognitive behavioral therapy and naltrexone may be synergistic BACKGROUND There is a large treatment gap in alcohol dependence , and current treatments are only moderately effective in preventing relapse . New treatment modalities , allowing for reduction of alcohol consumption as a treatment goal are needed . This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence . METHODS Six hundred and four patients ( placebo = 298 ; nalmefene = 306),≥18 years of age , with a diagnosis of alcohol dependence,≥6 heavy drinking days , and average alcohol consumption≥World Health Organization medium drinking risk level in the 4 weeks preceding screening , were r and omized ( 1:1 ) to 24 weeks of as-needed placebo or nalmefene  18 mg . RESULTS Patients taking placebo ( n = 289 ) and patients taking nalmefene ( n = 290 ) were included in the efficacy analyses . At Month 6 , there was a significant effect of nalmefene compared with placebo in reducing the number of heavy drinking days ( -2.3 days [ 95 % confidence interval:-3.8 to-.8 ] ; p = .0021 ) and total alcohol consumption ( -11.0 g/day [ 95 % confidence interval:-16.8 to-5.1 ] ; p = .0003 ) . Improvements in Clinical Global Impression and liver enzymes were larger in the nalmefene group compared with placebo at Week 24 . Adverse events ( most mild or moderate ) and dropouts due to adverse events were more common with nalmefene than placebo . The number of patients with serious adverse events was similar in the two groups . CONCLUSIONS Nalmefene provides clinical benefit , constitutes a potential new pharmacological treatment paradigm in terms of the treatment goal and dosing regimen , and provides a method to address the unmet medical need in patients with alcohol dependence that need to reduce their alcohol consumption Several studies have shown the opioid antagonist naltrexone to be effective when combined with psychosocial therapies for the treatment of patients who are dependent on alcohol with fixed medication and time ( 12 weeks ) . In this study , 121 nonabstinent out patients with alcohol dependence ( DSM-IV ) were treated with sessions of cognitive coping skills ( N = 67 ) or supportive therapy ( N = 54 ) and either naltrexone 50 mg/day ( N = 63 ) or placebo ( N = 58 ) daily for the first 12 weeks and thereafter for 20 weeks only when craving alcohol ( i.e. , targeted medication ) in a prospect i ve one-center , dual , double-blind , r and omized clinical trial . The dropout rate for all subjects was 16.5 % during the first 12-week period and approximately twice that level by the end of the study . There were no significant group differences in study completion and therapy participation rates . After the continuous medication ( 12 weeks ) , the coping/naltrexone group had the best outcome , and coping/placebo had the worst . This difference remained during the targeted medication period ( the following 20 weeks ) . Naltrexone was not better than placebo in the supportive groups , but it had a significant effect in the coping groups : 27 % of the coping/naltrexone patients had no relapses to heavy drinking throughout the 32 weeks , compared with only 3 % of the coping/placebo patients . The authors ’ data confirm the original finding of the efficacy of naltrexone in conjunction with coping skills therapy . In addition , their data show that detoxification is not required and that targeted medication taken only when craving occurs is effective in maintaining the reduction in heavy drinking BACKGROUND : Oral naltrexone is currently used as part of a treatment regimen for alcohol-dependent patients , but its clinical utility is hampered by poor patient adherence . A long-acting injectable naltrexone formulation ( Vivitrex ) was design ed to facilitate patient adherence by providing an extended duration of therapeutic naltrexone over 1 month , thereby eliminating the need for daily dosing . METHODS : A multicenter , r and omized , double-blind , placebo-controlled pilot study was conducted to evaluate the safety and tolerability of intramuscular repeat dose administration of this extended-release naltrexone formulation in DSM-IV alcohol-dependent patients . Thirty patients were r and omized to treatment with injectable naltrexone ( 400 mg ; n = 25 ) or a matching placebo injection ( n = 5 ) and were dosed once every 28 days over 4 months . Psychosocial treatment was offered to patients in both treatment groups . Outcome measures related to drinking activity and trough plasma concentrations of naltrexone and its primary metabolite , 6-beta-naltrexol , were evaluated . RESULTS : Injectable naltrexone was generally safe and well tolerated . Reported adverse events were mild to moderate and resolved without intervention ; only two patients discontinued due to adverse events . The most common adverse events ( nausea and headache ) occurred at a similar rate for patients in both treatment groups . Pharmacokinetic analysis confirmed that therapeutic levels of naltrexone were delivered throughout the four 1-month treatment cycles . CONCLUSIONS : The results of this pilot study provide the basis and methods for a larger , more definitive trial to determine the utility of this long-acting injectable naltrexone formulation in the treatment of alcohol-dependent patients A dozen studies have been published showing that opiate antagonists suppress alcohol drinking in animals , and two independent placebo-controlled , double-blind clinical trials of naltrexone found this agent was associated with decreased alcohol craving and consumption in alcohol-dependent patients .  Nalmefene is a newer opiate antagonist that has a number of potential advantages over naltrexone in the treatment of alcoholism , including no dose-dependent association with liver toxicity and more effective binding to central opiate receptors . Consequently , a double-blind pilot study was conducted to gather preliminary data on the safety and efficacy of nalmefene for reducing alcohol consumption in alcohol-dependent subjects . Twenty-one alcohol-dependent subjects meeting admission criteria were r and omly assigned to 12 weeks of double-blind treatment with 40 mg nalmefene , 10 mg nalmefene , or placebo , result ing in 7 patients /treatment group . Nalmefene was well tolerated , with no serious adverse drug reactions . The 40 mg group had a significantly lower rate of relapse ( p < or = 0.05 ) , and a greater increase in the number of abstinent days/week ( p < or = 0.09 ) , than the other treatment groups . A significant decrease in the number of drinks/drinking day was noted for both nalmefene groups ( p < or = 0.04 ) , but not for placebo . These results were supported by parallel decreases in ALT . These pilot data provide preliminary support for the hypotheses that nalmefene can be safely given to alcoholics , and that nalmefene may have a role in reducing alcohol consumption and preventing relapse , particularly at the 40 mg level . A full-scale study is underway to confirm these preliminary findings INTRODUCTION AND AIMS Prescribed psychotropic medications contribute to overdose mortality among people with alcohol and other drug ( AOD ) disorders . We report on prescribed psychotropic medication use among AOD treatment service attendees , focusing on sedative drugs . DESIGN AND METHODS Prospect i ve multi-site naturalistic outcome study in residential and outpatient AOD treatment facilities in Victoria and Western Australia . A convenience sample of 480 people ( 57 % male ; mean age 36.1 ) entering treatment were surveyed , of whom 313 ( 65 % ) were followed up by telephone interview after a median of 377 days . Participants ' prescribed psychotropic medication use was ascertained by self-report at baseline and follow-up . RESULTS At baseline , 41 % of participants reported prescribed sedative medication ( benzodiazepine , zopiclone or zolpidem ) use within the past month , including prescriptions to treat withdrawal symptoms . At follow-up , the cohort reported a reduced rate of past month prescribed sedative use ( 23 % ; P < 0.001 ) and this rate did not significantly differ between those who continued to use their primary drug of concern and those who were abstinent at follow-up ( P = 0.08 ) . Among those with opioids as their primary drug of concern , one-third were still being prescribed a sedative  at follow-up ( P > 0.99 for change from baseline ) . At baseline , 40 % of participants were prescribed an  antidepressant  and 13 % an  antipsychotic medication  , which remained similar at follow-up ( 45 % and 13 % , respectively ) . DISCUSSION AND CONCLUSIONS The high level of prescribed sedative drug use reported by people receiving AOD treatment is a serious public health concern given the increasing incidence of drug overdose deaths in Australia BACKGROUND There is growing evidence that pharmacological treatment with two of the best vali date d anticraving drugs , acamprosate and naltrexone , is efficacious in promoting abstinence in recently detoxified alcohol-dependent subjects . OBJECTIVE The stability of effects after termination of treatment remains to be answered , especially when combining both the drugs . METHOD After detoxification , 160 alcohol-dependent subjects participated in a r and omized , double-blind , placebo-controlled trial . Patients received naltrexone or acamprosate or a combination of naltrexone and acamprosate or placebo for 12 weeks . Patients were assessed weekly by interview , self-report , question naires and laboratory screening . Additionally , follow-up evaluation based on telephone interview of participants , general practitioners and relatives was conducted 12 weeks after terminating the medication . RESULTS At week 12 , the proportion of subjects relapsing to heavy drinking was significantly lower in the group with combined medication compared with both placebo and acamprosate ( P < 0.05 ) . No difference was detectable between acamprosate and naltrexone , both of which were superior to placebo ( P < 0.05 ) . Relapse rates were 28 % ( combined medication ) , 35 % ( naltrexone ) , 50 % ( acamprosate ) and 75 % ( placebo ) . After follow-up ( week 24 ) , combined medication led to relapse rates significantly lower than placebo , but not lower than acamprosate . Again , both naltrexone and acamprosate were superior to placebo . Relapse rates were 80 % ( placebo ) , 54 % ( acamprosate ) , 53 % ( naltrexone ) and 34 % ( combined medication ) . CONCLUSIONS The results of this study highlight the stability of effects of pharmacotherapy on relapse prevention in alcohol dependence Adolescent alcohol use is associated with myriad adverse consequences and contributes to the leading causes of mortality among youth . Despite the magnitude of this public health problem , evidence d‐based treatment initiatives for alcohol use disorders in youth remain inadequate . Identifying promising pharmacological approaches may improve treatment options . Naltrexone is an opiate receptor antagonist that is efficacious for reducing drinking in adults by attenuating craving and the rewarding effects of alcohol . Implication s of these findings for adolescents are unclear ; however , given that r and omized trials of naltrexone with youth are non‐existent . We conducted a r and omized , double‐blinded , placebo‐controlled cross‐over study , comparing naltrexone ( 50 mg/daily ) and placebo in 22 adolescent problem drinkers aged 15–19 years ( M = 18.36 , st and ard deviation = 0.95 ; 12 women ) . The primary outcome measures were alcohol use , subjective responses to alcohol consumption , and alcohol – cue‐elicited craving assessed in the natural environment using ecological momentary assessment methods , and craving and physiological reactivity assessed using st and ard alcohol cue reactivity procedures . Results showed that naltrexone reduced the likelihood of drinking and heavy drinking ( P 's ≤ 0.03 ) , blunted craving in the laboratory and in the natural environment ( P 's ≤ 0.04 ) , and altered subjective responses to alcohol consumption ( P 's ≤ 0.01 ) . Naltrexone was generally well tolerated by participants . This study provides the first experimentally controlled evidence that naltrexone  reduces drinking and craving , and alters subjective responses to alcohol in a sample of adolescent problem drinkers , and suggests larger clinical trials with long‐term follow‐ups are warranted
target: 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 .
background: Background : Sleep disorders are commonly associated with acute and chronic use of alcohol and with abstinence .
  To date , there are four approved drugs to treat alcohol use disorder ( AUD ) : disulfiram , acamprosate , naltrexone , and nalmefene .
  These AUD therapies reduce the craving and risk of relapse into heavy drinking , but little is known about their effect on sleep .
  As recent evidence s indicate a crucial role of sleep disorders in AUD , cl aim ing that sleep problems may trigger alcohol abuse and relapses , it is fundamental to clarify the impact of those drugs on the sleep quality of AUD patients .
  This systematic review aims to answer the question : how does the pharmacotherapy for AUD affect sleep ?