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Effects of acamprosate and some polyamine site ligands of NMDA receptor on short-term memory in rats.

The aim of this study was to evaluate the effect of multiple acamprosate (500.0 mg/kg, p.o.) administration on short-term memory, using the social recognition test in rats. Ifenprodil (1.0 mg/kg, i.p.), arcaine (5.0 mg/kg, i.p.) and spermidine (20.0 mg/kg, i.p.) were chosen as polyamine ligands and their action or interaction with acamprosate was also studied. The doses used did not show any sedative activity, which was assessed by measuring locomotor activity and the hypnotic effect of ethanol. The findings suggest that acute acamprosate treatment did not impair short-term memory. Multiple acamprosate and a single spermidine or arcaine administration led to better performance in the memory test, whereas no significant difference was observed in ifenprodil-treated rats. Co-administration of a single arcaine or spermidine dose with multiple acamprosate produced worse results. This means that the effect of repeated acamprosate administration can be changed by the co-administration of other polyamine ligands, so that care should be taken in interpreting.

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The anti-craving drug acamprosate reduces c-fos expression in rats undergoing ethanol withdrawal.

Acamprosate (Ca salt of N-acetylhomotaurine) is a novel anti-craving substance which a double-blind placebo-controlled study has proven to be therapeutically useful in the prevention of relapses in weaned alcoholics. In the present study the expression of the immediate-early gene c-fos in rat hippocampal and cerebellar neurons was used to monitor the modulatory effect of acamprosate on neuronal excitability during ethanol withdrawal. Several hybridization techniques were employed to investigate the effect of acamprosate on c-fos expression. Acamprosate (200 mg/kg; intraperitoneally) reduced the elevated c-fos mRNA levels in the hippocampus and the cerebellum following 24 h of ethanol withdrawal, or the application of the convulsant pentylenetetrazole. The effect of ethanol withdrawal on c-fos expression was more pronounced in the cerebellum than in the hippocampus. In the hippocampus (CA1) and the cerebellum acamprosate alone induced a significant increase in c-fos expression in drug-naive animals. Only in the hippocampus did co-administration of pentylenetetrazole during ethanol withdrawal induce a further increase in c-fos expression. The present findings support the notion that acamprosate elicits its preventive effect on relapse by reducing the hyperexcitability of central neurons during withdrawal, following long-term ethanol consumption.

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Acamprosate does not induce a conditioned place preference and reveals no state-dependent effects in this paradigm.

To evaluate the putative rewarding properties of the anticraving substance acamprosate, male rats learned to associate injections of vehicle and acamprosate (200 mg/kg ip) with two visually contrasting compartments in a place conditioning paradigm. The degree of preference for the acamprosate-associated compartment was determined, in both a postconditioning test with undrugged animals and a consecutive test with drugged animals, to rule out the possibility that a putatively rewarding effect of acamprosate may have been masked by state-dependent effects. The animals did not show any preference for the substance-paired compartment, neither in the undrugged nor in the drugged state. In conclusion, acamprosate has no rewarding properties as shown in place preference. Therefore, it may prevent a relapse in detoxified alcoholics in a way other than by simply substituting the rewarding effects of ethanol. This adds to the therapeutic value of acamprosate in the treatment of drug craving.

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Effects of naltrexone alone and in combination with acamprosate on the alcohol deprivation effect in rats.

Previous research in our laboratory has shown that responding for ethanol increases after a period of imposed deprivation during which no ethanol is available (the alcohol deprivation effect). This selective increase in responding for ethanol was blocked by chronic administration of acamprosate. In the present study the effects of naltrexone and the combination of naltrexone+acamprosate on oral ethanol self-administration were examined following an imposed period of abstinence. Male Wistar rats were trained to respond for ethanol (10% w/v) or water in a two-lever free-choice condition. After training, separate groups of rats received chronic injections (2 x /day) of saline, naltrexone, or naltrexone+acamprosate during a 5-day period of abstinence. Ethanol self-administration was tested in all groups of rats on the last day of abstinence, 30 min after the last drug injection. Responding for ethanol increased significantly following the deprivation period in animals treated with saline. Chronic administration of naltrexone and the combination naltrexone+acamprosate blocked the increased ethanol consumption following the imposed abstinence period on post-deprivation Day 1. On post-deprivation Day 2, the combination of acamprosate with naltrexone blocked the rebound increase in ethanol consumption observed in animals treated with a low dose of naltrexone. These results support the hypothesis that naltrexone and acamprosate are effective in modulating aspects of alcohol-seeking behavior, and under certain situations may be more effective in combination.

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Clinical characterization of use of acamprosate and naltrexone: data from an addiction center in India.

There are several queries on the effectiveness of acamprosate in pharmacoprophylaxis of alcohol dependence despite studies conducted over the last decade regarding its efficacy. In this retrospective chart review, 62 patients with ICD-10-diagnosed alcohol dependence who received treatment from an addiction center in India were studied to compare those on acamprosate or naltrexone versus those on no prophylactic drugs with regard to their demographic and clinical background and short-term outcome after treatment. Compared to those on naltrexone or no drugs, significantly more patients on acamprosate came from higher socioeconomic strata and had fewer family/marital complications and less comorbid use of opioids and other drugs; however, they also had more liver function impairment and alcoholic liver disease and a higher average duration of relapse in the past (p < 0.05 or less in each case). The group on no drugs had significantly less family/social support (p = 0.006) and poorer motivation rating (p < 0.001) than the other two groups on drugs. Intent-to-treat analysis showed that there was a non-significant trend of a higher proportion of acamprosate patients remaining abstinent (77%) than those on naltrexone (36%) or no drug (50%). At follow-up, acamprosate patients had significantly better functioning in several areas. However, because many of the baseline patient characteristics might themselves have influenced the outcome, no conclusion should be drawn from this data regarding the efficacy of the drug. Logistic regression analysis showed that both family/social support and acamprosate appeared to contribute modestly toward explaining the variance in short-term outcome.

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Acamprosate and relapse prevention in the treatment of alcohol dependence: a placebo-controlled study.

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 randomized 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.

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Acamprosate in Korean alcohol-dependent patients: a multi-centre, randomized, double-blind, placebo-controlled study.

AIMS: A multi-centre, randomized, 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 randomized 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 standard 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.

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Acamprosate and diazepam differentially modulate alcohol-induced behavioural and cortical alterations in rats following chronic inhalation of ethanol vapour.

The effects of Acamprosate (the calcium salt of an acetylated form of homotaurine) and the benzodiazepine-receptor agonist Diazepam, were investigated on the alcohol-induced behavioural preference towards alcohol following chronic alcoholization by inhalation. We also examined the effects of Acamprosate and Diazepam on the blood alcohol level (BAL) and on the cortical microvascular network. Acamprosate (50, 100, 200 and 400 mg/kg daily per os during the alcoholization period) did not significantly reduce either BAL or alcohol-induced cortical hypervascularization. Increasing dosages of Acamprosate (i.e. 50, 100, and 200 mg/kg/day), however, progressively reduced preference for alcohol as expressed in a free choice beverage procedure, whereas 400 mg/kg/day of Acamprosate immediately stopped this behaviour. Acamprosate (50 mg/kg/day) also reduced the spontaneous activity of rats during the withdrawal syndrome. By contrast, Diazepam (5 mg/kg) induced inversion in the animals' choice (i.e. increased water consumption versus decreased alcohol intake) during the same experimental procedure, and potentiated the alcohol-induced hypermotility of the animals during the withdrawal syndrome without altering cortical hypervascularization. Taken together, our data provide evidence that both substances exert dose-dependent effects on preference towards alcohol, but display opposite profiles on spontaneous motor activity during the withdrawal phase without any modification of brain microvascularization or blood alcohol levels.

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Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects.

We examined kinetic and dynamic factors to determine the pharmacological and behavioral safety and tolerability of low versus high doses of an opiate antagonist, naltrexone (50 mg/day vs. 100 mg/day), and acamprosate (2 g/day vs. 3 g/day), a functional N-methyl-D-aspartate receptor antagonist, both independently and combined, among non-treatment-seeking, alcohol-dependent individuals. This double-blind, double-dummy, placebo-controlled, randomized, 23-day, four-way crossover study involved 23 subjects assigned to one of four groups. Placebo washout (phase I) preceded phase II, where subjects received low-dose or high-dose naltrexone or acamprosate. In phases III and IV, the alternative medication type at its lower and higher doses, respectively, was administered with continuation of the phase II medication. Predetermined behavioral, performance, and pharmacological criteria determined significant pathological change from baseline (phase I). Case records were reviewed. Criterion-significant increases in symptoms from baseline with monotherapy included nervousness and fatigue with 3 g acamprosate and somnolence and headache with 50 mg and 100 mg naltrexone, respectively. Combined treatment at various doses evinced anger, depression, somnolence, nervousness, diarrhea, and headache. Notably, for all but one subject who dropped out, increased symptoms did not produce any remarkable clinical deterioration. Naltrexone administration significantly increased plasma acetylhomotaurine (i.e., acamprosate) levels, presumably by prolonging gastric emptying. The level of neither plasma acetylhomotaurine nor plasma 6-beta naltrexol (i.e., naltrexone's metabolite) predicted adverse-event frequency. Naltrexone and acamprosate, both alone and in combination at the tested doses, were behaviorally and pharmacologically safe. Adverse events were infrequent, were of moderate intensity, and resolved with reassurance and symptomatic treatment. More side effects were noted with the combination of medications than with either medication alone. Naltrexone administration significantly increased plasma acamprosate levels.

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Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review.

AIMS: To ascertain the efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence. METHODS: Systematic review of the literature (1990-2002) and meta-analysis of full published randomized and controlled clinical trials assessing acamprosate or naltrexone therapy in alcohol dependence. Estimates of effect were calculated according to the fixed-effects model. MEASUREMENTS: Relapse and abstinence rates, cumulative abstinence duration and treatment compliance were considered as primary outcomes. Findings Thirty-three studies met the inclusion criteria. Acamprosate was associated with a significant improvement in abstinence rate [odds ratio (OR): 1.88 (1.57, 2.25), P < 0.001] and days of cumulative abstinence [WMD: 26.55 (17.56, 36.54]. Short-term administration of naltrexone reduced the relapse rate significantly [OR: 0.62 (0.52, 0.75), P < 0.001], but was not associated with a significant modification in the abstinence rate [OR: 1.26 (0.97,1.64), P = 0.08]. There were insufficient data to ascertain naltrexone's efficacy over more prolonged periods. Acamprosate had a good safety pattern and was associated with a significant improvement in treatment compliance [OR: 1.29 (1.13,1.47), P < 0.001]. Naltrexone's side effects were more numerous, yet the drug was nevertheless tolerated acceptably without being associated with a lower adherence to treatment (OR: 0.94 (0.80, 1.1), P = 0.5). However, overall compliance was relatively low with both medications. CONCLUSIONS: Both acamprosate and naltrexone are effective as adjuvant therapies for alcohol dependence in adults. Acamprosate appears to be especially useful in a therapeutic approach targeted at achieving abstinence, whereas naltrexone seems more indicated in programmes geared to controlled consumption. Both drugs are safe and acceptably tolerated but issues of compliance need to be addressed adequately to assure their usefulness in clinical practice.

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Schedule-induced alcohol drinking: non-selective effects of acamprosate and naltrexone.

Acamprosate and naltrexone are therapeutically effective drugs that promote abstinence and prevent drinking relapse among alcohol-dependent patients, and dose-dependently decrease alcohol self-administration in animals. The purpose of this experiment was to investigate the behavioral specificity of acamprosate and naltrexone treatment in mice on alcohol drinking elicited in a schedule-induced polydipsia (SIP) task. Food-deprived male C57BL/6J (B6) mice were divided into three groups assigned to a 5% alcohol SIP, water SIP, or a 1-hour limited access regulatory water drinking task. Injections (intraperitoneal) of acute (0, 50, 100, 200, 400 mg/kg) and chronic (2 x 100 mg/kg, 10 days) acamprosate, or naltrexone (0, 1.0, 2.5, 5.0 mg/kg) were administered. Behavioral drug specificity was determined by comparing alterations in alcohol or water consumption in SIP with alterations in limited access drinking. Additionally, drug effects on drinking-specific measures (g/kg consumption and lick efficiency) were compared with those of non-drinking measures (head entries for food and locomotor activity) during SIP. In comparison with saline injections, acute acamprosate (400 mg/kg) reduced both alcohol and water drinking in both SIP and the regulatory drinking conditions, but had no significant effects on non-drinking measures. Chronic administration of acamprosate reduced both alcohol and water drinking during SIP, but did not significantly affect regulatory drinking or non-drinking measures. Naltrexone (1.0, 2.5, 5.0 mg/kg) reduced alcohol and water drinking in both paradigms, and at the highest dose, significantly reduced head entries for food. These results indicate that acamprosate (acute and chronic) and naltrexone are relatively non-selective in their effects on alcohol self-administration in this task.

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Pharmacology of acamprosate: an overview.

In the last years important advances have been made in the development of drugs for the treatment of alcohol addiction. Acamprosate (calcium bis-acetylhomotaurine) is one of the better established drugs in this field on the European market. This review focuses first on the pharmacokinetics of acamprosate. The published data and the recent advances in our knowledge on the mechanisms involved in the intestinal absorption and elimination of this drug are summarized. The importance of pharmacokinetics for the proper clinical use of acamprosate is highlighted. The anti-relapse as well as the well-known effects of acamprosate on ethanol intake are discussed. The recent experiments in animal models of conditioned withdrawal are reviewed. These experiments, explored for the first time the anticraving effect of the drug. Finally, the proposed hypotheses on the neuropharmacological mechanism of action of acamprosate are discussed. The discussion deals with the relative importance of various hypotheses as well as with the recent experiments that support them. It is pointed out that further research is necessary in order to clearly understand the mode of action of acamprosate as well as the neurobiological mechanisms involved in alcohol dependence.

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Effects of acamprosate on sleep during alcohol withdrawal: A double-blind placebo-controlled polysomnographic study in alcohol-dependent subjects.

BACKGROUND: Sleep disturbances are frequently encountered in alcohol-dependent patients. Drugs improving sleep during abstinence from alcohol may play an important role in the recovery process. METHODS: In the present study, the effects of acamprosate, a drug successfully used in maintaining abstinence following alcohol withdrawal, were assessed by polysomnographic recordings. A parallel double-blind placebo-controlled study was conducted in 24 male DSM-IV alcohol-dependent subjects aged 35.9+/-1.2 years. Treatments (2 tablets of 333 mg acamprosate vs placebo t.i.d.) were initiated 8 days before alcohol withdrawal and continued during the 15 days following alcohol withdrawal. Polysomnographic assessments were recorded during acute withdrawal (the first 2 nights following withdrawal) and during postwithdrawal abstinence (the last 2 nights of the trial). RESULTS: Results show that, compared with placebo, acamprosate decreased wake time after sleep onset and increased stage 3 and REM sleep latency (all treatment effects with a p < 0.05 significance). Withdrawal effects themselves were also demonstrated as sleep efficiency (p < 0.01) and total sleep time (p < 0.05) were lower in abstinence nights versus withdrawal nights, whereas no significant treatment x withdrawal effect could be evidenced. Acamprosate was well tolerated during the entire course of the study. CONCLUSIONS: The present study shows that acamprosate ameliorates both sleep continuity and sleep architecture parameters classically described as disturbed in alcohol-dependent patients. From a clinical perspective, it suggests that an 8-day acamprosate prewithdrawal treatment is well tolerated and can attenuate the sleep disturbances engendered by alcohol withdrawal in alcohol-dependent subjects.

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Pharmacodynamic effects of acamprosate on markers of cerebral function in alcohol-dependent subjects administered as pretreatment and during alcohol abstinence.

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, randomised, 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 evidenced 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.

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Acamprosate for the adjunctive treatment of alcohol dependence.

OBJECTIVE: To review the literature related to the treatment of alcohol dependence with acamprosate, a synthetic compound structurally similar to the naturally occurring amino acid, homotaurine. DATA SOURCES: Primary literature and review articles were identified by MEDLINE search (1966-June 2003). Abstracts from recent meetings were also reviewed. DATA SYNTHESIS: Acamprosate has been marketed in 24 countries. Although the precise mechanism of acamprosate in the treatment of alcohol-dependent patients is unclear, it may restore the balance between inhibitory and excitatory neurotransmission in the central nervous system. European trials have shown consistent increases in abstinence rates compared with placebo when acamprosate use was paired with appropriate psychosocial and behavioral therapies. Decreased direct and indirect healthcare costs associated with acamprosate treatment have also been reported. CONCLUSIONS: Acamprosate is a promising medication for the treatment of alcohol dependence in the US.

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Acamprosate in the treatment of alcohol dependence.

Acamprosate is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation in combination with psychosocial support. Acamprosate is a synthetic taurine analogue that seems to act centrally to restore the normal activity of glutamatergic neurotransmission altered by chronic alcohol exposure. Over the past 15 years, the safety and efficacy of acamprosate for alcohol dependence have been well established in multiple double-blind, placebo-controlled trials. Overall, acamprosate has been consistently associated with greater beneficial effects on measures of alcohol abstinence compared with placebo. Specifically, patients treated with acamprosate achieve greater rates of complete abstinence, longer times to first drink and/or increased duration of cumulative abstinence when compared with placebo. Acamprosate received approval by the US FDA for the treatment of alcohol dependence in July 2004 and is currently prescribed in 28 countries.

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Treatment of alcohol-dependent outpatients with acamprosate: a clinical review.

Acamprosate (calcium acetyl-homotaurine) is a synthetic compound whose chemical structure resembles that of homotaurine, a naturally occurring amino acid. Acamprosate acts centrally and appears to restore the normal activity of glutaminergic neurons, which become hyperexcited as a result of chronic alcohol exposure. Although not yet approved for use in the United States, acamprosate has been available by prescription in France since 1989 and is now available in many other countries throughout the world. This article reviews data from all published double-blind, placebo-controlled clinical trials of acamprosate among alcohol-dependent outpatients. Overall, patients treated with acamprosate exhibited a significantly greater rate of treatment completion, time to first drink, abstinence rate, and/or cumulative abstinence duration than patients treated with placebo. The drug's reliable effect on prolonging abstinence, in conjunction with an excellent safety profile, suggests that acamprosate may be useful for a broad range of patients with alcohol dependence.

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Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol.

A prospective placebo-controlled, randomized double-blind study of Acamprosate at two dose levels in alcohol-dependent patients followed up for 12 months was performed. After detoxification, each of the 538 patients included was randomly assigned to one of three groups: 177 patients received placebo, 188 received Acamprosate at 1.3 g/day (low dose group) and 173 received 2.0 g/day (high dose group) for 12 months. This was followed by a single blind 6 month period on placebo. The patients' mean age was 43.2 +/- 8.6 years. Their mean daily alcohol intake was high (nearly 200 g/day) and of long duration (9.5 +/- 7.1 years). Abstinence figures followed the order high dose > low dose > placebo. The difference was significant at 6 months (P < or = 0.02) but not at 12 months (P = 0.096). The number of days of continuous abstinence after detoxification was 153 +/- 197 for the high-dose group versus 102 +/- 165 for the placebo group (P = 0.005), with the lose-dose group reporting 135 +/- 189 days. Clinic attendance was significantly better in the Acamprosate groups than in the placebo group at 6 months (P = 0.002) and 12 months (P = 0.005). During the 6-month post-treatment period, no increased relapse rate or residual drug effect was observed. The side effect profile for Acamprosate was good compared with controls with only diarrhoea being reported more frequently (P < 0.01). This study confirms the pharmacological efficacy of Acamprosate and its good acceptability. As an adjunct to psychotherapy, this study supports the inclusion of Acamprosate in a strategy for treating alcoholism.

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