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PubMed1998

Acamprosate suppresses the expression of morphine-induced sensitization in rats but does not affect heroin self-administration or relapse induced by heroin or stress.

Acamprosate (calcium-acetyl homotaurinate) is a new compound used in the treatment of alcohol abuse. Because of the putative link between alcoholism and the endogenous opioid systems in both humans and laboratory animals, we tested in rats the effects of acamprosate on behavioral and neurochemical effects of opioid drugs related to their abuse potential. These included sensitization to the behavioral effects of morphine, morphine-induced dopamine (DA) release in the nucleus accumbens (NAS), intravenous (i.v.) heroin self-administration and relapse to heroin seeking in drug-free rats. In experiment 1, rats were injected daily with either morphine (10 mg/kg, s.c.) or saline for 14 days. Three days later in a test for the expression of sensitization, an injection of morphine (10 mg/kg) resulted in increased locomotor activity and enhanced DA release in the NAS in rats previously exposed to morphine. Acamprosate (two injections of 200 mg/kg, 12 h apart; i.p.) suppressed the expression of the sensitized responses, but did not alter the effects of morphine in drug-naive control rats. In experiment 2, it was found that acamprosate (two injections of 50-200 mg/ kg; i.p.) had no consistent effects on i.v. heroin self-administration (50 100 microg/kg per infusion) and, in experiment 3, that acamprosate (100-200 mg/ kg, i.p.) did not alter reinstatement of drug seeking induced by priming injections of heroin (0.25 mg/kg, s.c.) or a footshock stressor (15 min; 0.5 mA) after a 5- to 8-day period of extinction. Thus, although acamprosate attenuated the expression of sensitized locomotor activity and DA release in the NAS, it did not have any consistent effect on either the intake of heroin during the maintenance phase or the relapse to heroin seeking in a drug-free state. Thus, to the extent that the self-administration and the reinstatement procedures provide valid preclinical models for drug use and relapse in humans, our data suggest that acamprosate may not be effective in altering drug-taking behavior in heroin users.

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PubMed2003

Acamprosate and its efficacy in treating alcohol dependent adolescents.

BACKGROUND: About 50 % of adult 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 of adolescents. METHODS: In this, double-blind, placebo-controlled study, we recruited 26 patients, aged 16-19 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1332 mg daily) or placebo for 90 days. Patients were assessed on the day treatment started and on days 30, and 90 by interview, self report, questionnaire, and laboratory screening. FINDINGS: 13 acamprosate-treated and 13 placebo-treated patients completed the treatment phase: of those withdrawn, 11 (1 vs 6) relapsed, 5 (3 vs 2) refused to continue treatment, 3 (1 vs 2) had concurrent illness, and 2 (1 vs 1) had adverse side-effects. At the end of treatment, 7 acamprosate treated and 2 placebo-treated patients had been continuously abstinent (p = 0.0076). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (79.8 [SD 37.5] vs 32.8 [19.0] days; p = 0.012). INTERPRETATION: Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial treatment programmes.

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PubMed1992

Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats.

Male Sprague-Dawley rats were pulmonary alcoholised for 30 days. Six were treated with acamprosate (400 mg/kg/day, PO) during alcoholisation. The control nonalcoholised group also received acamprosate (400 mg/kg/day, PO) during the 30 days. At the end of the experiment, brains areas (cortex, hippocampus, thalamus, striatum, and olfactory bulbs) were dissected for the study of synaptosomal 3H-GABA uptake. In another experiment, GABA levels were determined in the same areas using HPLC with electrochemical detection. Blood ethanol levels were also measured during alcoholisation. Acamprosate treatment did not modify blood ethanol levels. In cortex and olfactory bulbs, alcoholisation increased 3H-GABA uptake (Vmax) with an increase in the affinity (Km). 3H-GABA uptake was not affected by alcoholisation in other brain areas. In hippocampus and thalamus, acamprosate treatment enhanced 3H-GABA uptake (Vmax) only in alcoholised rats. Moreover, in thalamus, alcoholisation enhanced GABA levels. The effect of alcohol and acamprosate on GABA presynaptic events is discussed and it is concluded that the action of ethanol and acamprosate on GABA transport could be, in part, responsible for the modulation by acamprosate treatment of ethanol behaviour.

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PubMed2000

Interaction of acamprosate with ethanol and spermine on NMDA receptors in primary cultured neurons.

The N-methyl-D-aspartate (NMDA) receptor has been implicated as a putative sight of action for acamprosate, a novel drug that reduces craving for alcohol. The purpose of this study was to assess the effect of acamprosate on the function of native NMDA receptors expressed in primary cultured striatal and cerebellar granule cells, as well as ethanol inhibition and spermine modulation of these receptors, using whole-cell patch-clamp electrophysiological techniques. Under all circumstances, acamprosate (0.1-300 microM) did not alter NMDA- or glutamate-induced currents. Acamprosate did not alter the inhibitory effects of ethanol (10-100 mM) on receptor function. In a subpopulation of striatal neurons, acamprosate did reverse the potentiating effects of spermine. These findings indicate that although acamprosate may modify polyamine modulation of the NMDA receptor, acamprosate alone does not alter receptor function nor does it modify ethanol inhibition of this receptor expressed in primary cultured striatal and cerebellar granule neurons.

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PubMed2001

The anti-craving compound acamprosate acts as a weak NMDA-receptor antagonist, but modulates NMDA-receptor subunit expression similar to memantine and MK-801.

NMDA-receptor-mediated mechanisms may be crucial in addictive states, e.g. alcoholism, and provide a target for the novel anti-craving compound acamprosate. Here, the pharmacological effects of acamprosate on NMDA-receptors were studied using electrophysiological techniques in different cell lines in vitro. Additionally, a possible modulation of brain NMDA-receptor subunit expression was examined in vivo in rats, and compared to two effective non-competitive NMDA-receptor antagonists, memantine and MK-801. Electrophysiology in cultured hippocampal neurons (IC(50) approx. 5.5mM) and Xenopus oocytes (NR1-1a/NR2A assemblies: IC(50) approx. 350 microM, NR1-1a/NR2B: IC(50) approx. 250 microM) consistently revealed only a weak antagonism of acamprosate on native or recombinant NMDA-receptors. In HEK-293 cells, acamprosate showed almost no effect on NR1-1a/NR2A or NR1-1a/NR2B recombinants (IC(50)s not calculated). Protein blotting demonstrated an up-regulation of NMDA-receptor subunits after acamprosate as well as after memantine or MK-801, in comparison to controls. After acamprosate, protein levels were increased in the cortex (NR1-3/1-4: 190+/-11% of controls) and hippocampus (NR1-1/1-2: 163+/-11%). The up-regulations observed after memantine (cortex, NR2B: 172+/-17%; hippocampus, NR1-1/1-2: 156+/-8%) or MK-801 (cortex, NR2B: 174+/-22%; hippocampus, NR1-1/1-2: 140+/-3%) were almost identical. No changes were detected in the brainstem. The present data indicate an extremely weak antagonism of NMDA-receptors by acamprosate. However, its ability to modulate the expression of NMDA-receptor subunits in specific brain regions - shared with the well established NMDA-antagonists memantine and MK-801 - may be of relevance for its therapeutic profile, especially considering the growing importance of NMDA-receptor plasticity in the research of ethanol addiction.

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PubMed2001

[Adjuvant drug treatment of alcoholism with acamprosate: between sectoral budgets and disease management].

OBJECTIVE: On the basis of several controlled clinical investigations the cost-effectiveness of acamprosate as adjuvant therapy of alcohol-dependent patients has yet been evaluated. These optimal conditions cannot be found in the daily ambulant practice and results in asking which of the alternatives, "standard plus acamprosate" or "standard without acamprosate", is more cost-effective in maintaining abstinence in alcohol dependent patients under realistic conditions. PATIENTS AND METHODS: In an open multi-centre study, medical care, costs and therapeutic outcome was prospectively documented. Prior to enrolling, all patients were obliged to undergo a detoxification procedure. At a mean age of 45 years the patients suffered an average of ten years from alcohol dependence. 521 patients were documented in the acamprosate cohort and 265 patients in the cohort "other therapy" over one year. Two thirds of the participating patients were male. RESULTS: At 33.6 % the rate of abstinence was remarkably higher in the acamprosate cohort in comparison to the cohort "other" at 21.1 % abstinent patients. The mean total costs per patient and year amounted to DM 3191 in the acamprosate-cohort and were significantly lower than in the cohort "other" with DM 4046. Effectiveness-adjusted costs of DM 9500 per successfully treated patient in the acamprosate-cohort were superior to the cohort "other", amounting to DM 19 148 per successfully treated patient. CONCLUSION: The described economic benefits may be utilised under conditions of an adequate disease management.

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PubMed2004

Hypothalamic-pituitary-adrenal system regulation in recently detoxified alcoholics is not altered by one week of treatment with acamprosate.

BACKGROUND: Acamprosate decreases relapse rates in alcohol-dependent patients by approximately 10-20% within the first year after detoxification. Psychological stress is a major risk fac-tor for relapse and is associated with activation of the hypothalamic-pituitary-adrenocortical (HPA) system. In recently detoxified alcoholics, the HPA system is dysregulated with non-suppression of cortisol after dexamethasone administration. We therefore investigated whether acamprosate normalizes HPA hyperactivity in alcoholics within the first 3 weeks of abstinence, employing a combined dexamethasone/corticotropin-releasing hormone (Dex-CRH)-test. METHODS: Thirty alcohol-dependent patients were tested one week after withdrawal signs had disappeared. In 15 patients, acamprosate, 1332-1998 mg/day, was administered orally and a second Dex-CRH test was performed 1 week later. In the other 15 patients, acamprosate treatment was offered only after the second test. RESULTS: CRH-stimulated cortisol secretion was significantly increased in both the acamprosate group and the group receiving no anti-relapse medication compared to a control group of 15 healthy subjects. Acamprosate treatment had no effect on basal or CRH-stimulated ACTH or cortisol secretion. CONCLUSIONS: We conclude that 1 week of acamprosate treatment does not attenuate the HPA dysregulation ob-served during early abstinence.

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PubMedDate not supplied

Naltrexone versus acamprosate: one year follow-up of alcohol dependence treatment.

Naltrexone and acamprosate reduce relapse in alcohol dependence. They have not yet been compared in a published trial. The aim of this study was to compare the efficacy of these compounds in conditions similar to those in routine clinical practice. Random allocation to a year of treatment with naltrexone (50 mg/day) or acamprosate (1665-1998 mg/day) was made in 157 recently detoxified alcohol-dependent men with moderate dependence (evaluated using the Addictions Severity Index and Severity of Alcohol Dependence Scale). All were patients whom a member of the family would accompany regularly to appointments. Alcohol consumption, craving and adverse events were recorded weekly for the first 3 months, and then bi-weekly, by the treating psychiatrist who was not blinded. At 3-monthly intervals, investigators who were blinded to the treatment documented patients' alcohol consumption based on patients' accounts, information given by the psychiatrists when necessary, and reports from patients' families. Serum gamma-glutamyltransferase (GGT) was also measured. Efforts were made to sustain the blindness of the investigators. The same investigator did not assess the same patient twice. The integrity of the blindness was not checked. There was no difference between treatments in mean time to first drink (naltrexone 44 days, acamprosate 39 days) but the time to first relapse (five or more drinks in a day) was 63 days (naltrexone) versus 42 days (acamprosate) (P = 0.02). At the end of 1 year, 41% receiving naltrexone and 17% receiving acamprosate had not relapsed (P = 0.0009). The cumulative number of days of abstinence was significantly greater, and the number of drinks consumed at one time and severity of craving were significantly less, in the naltrexone group compared to the acamprosate group, as was the percentage of heavy drinking days (P = 0.038). More patients in the acamprosate than the naltrexone group were commenced on disulfiram during the study. Naltrexone patients attended significantly more group therapy sessions, though this could not explain their better outcome. There were non-significant trends for the naltrexone group to comply better with medication, to stay in the study longer, and to show greater improvement over baseline in serum GGT.

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PubMedDate not supplied

Does psychosocial treatment enhance the efficacy of acamprosate in patients with alcohol problems?

AIMS: Acamprosate in combination with psychosocial treatment has been shown to be effective for the treatment of alcohol dependence. The goal of the present study was to determine whether the addition of psychosocial intervention to the medical prescription of acamprosate contributes to treatment outcome. METHODS: Patients (n = 248) meeting DSM-IV criteria for alcohol dependence or abuse were recruited in 14 outpatient treatment centres and randomized into one of three treatment conditions: acamprosate; acamprosate plus minimal intervention aimed at motivational enhancement (3-weekly sessions of 20 min); and acamprosate plus brief cognitive behavioural therapy (7-weekly sessions of 60 min). Acamprosate was prescribed for 28 weeks, medically monitored by a physician on six occasions lasting 10 min. Drinking behaviour, medication compliance and psychological distress were assessed throughout the treatment period. Follow-up assessment was undertaken 6 months after termination of pharmacological treatment. RESULTS: Of 241 patients with intention to treat (ITT), 114 (47.3%) remained in treatment for the full 28 weeks; 169 of the ITT population (70.1%) were seen for follow-up. No statistically significant differences were found between treatment groups for any of the drinking outcomes either at the end of the 28 weeks of treatment or at 6-month follow-up. There were no statistically significant differences in medication compliance, drop-out rates, or psychological distress. However, a significant interaction effect was observed between treatment centre and treatment group, indicating that brief interventions were differentially effective in different treatment centres. CONCLUSIONS: A clear supplemental value of minimal and brief psychosocial interventions to the prescription of acamprosate was not demonstrated. The widely held belief that pharmacotherapy for alcohol dependence should always be combined with psychosocial intervention is debatable and merits further research.

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PubMed2003

Effects of acamprosate on excitatory amino acids during multiple ethanol withdrawal periods.

BACKGROUND: Our previous studies on the effects of acamprosate on enhanced locomotion during repeated withdrawals are now extended to the effects of acamprosate on excitatory amino acids in the hippocampus during repeated ethanol withdrawals. METHODS: In this study, Wistar rats were made ethanol dependent by 4 weeks of vapor inhalation. After this first cycle of chronic ethanol treatment, rats underwent repeated and alternate cycles of 24 hr withdrawals and 1 week of chronic ethanol treatment. The microdialysis technique was used together with high-performance liquid chromatography and electrochemical detection to quantify different amino acids such as aspartate and glutamate. RESULTS: An intraperitoneal administration of acamprosate (400 mg/kg) to naïve rats did not alter aspartate or glutamate levels compared with the saline groups. During the first cycle of ethanol withdrawal, the administration of acamprosate (400 mg/kg, intraperitoneally) 2 hr after the commencement of ethanol withdrawal decreased both aspartate and glutamate microdialysate levels when compared with their respective saline group. Acamprosate administration also significantly decreased glutamate levels during the third withdrawal compared with the saline group, whereas no changes were seen in aspartate levels. CONCLUSION: The results of this work demonstrate that acamprosate reduced the excitatory amino acid glutamate increase observed during repeated ethanol withdrawal. These effects of acamprosate may provide a protective mechanism against neurotoxicity by reducing excitatory amino acids, particularly glutamate.

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PubMed2004

The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis.

BACKGROUND: A number of clinical trials have been undertaken to determine the efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals. However, the reported differences in patient populations, treatment duration, and study endpoints make comparisons difficult. An assessment of the efficacy of treatment with acamprosate was, therefore, undertaken using meta-analytical techniques. METHODS: All randomized, placebo-controlled trials (RCTs) that fulfilled predetermined criteria were identified using (1) a language unrestricted search of 10 electronic databases; (2) a manual search of relevant journals, symposia, and conference proceedings; (3) cross-referencing of all identified publications; (4) personal communications with investigators; and (5) scrutiny of Merck-Santé's internal reports of all European trials. Study quality was assessed, independently, by three blinded workers. Key outcome data were identified; some outcome variables were recalculated to ensure consistency across trials. The primary outcome measure was continuous abstinence at 6 months; abstinence rates were determined by estimating Relative Benefit (RB). RESULTS: A total of 19 published 1 unpublished RCTs were identified that fulfilled the selection criteria; 3 were excluded because the documentation available was insufficient to allow adequate assessment. The remaining 17 studies, which included 4087 individuals, 53% of whom received active drug, were of good quality and were otherwise reasonably comparable. There was no evidence of publication bias. Continuous abstinence rates at 6 months were significantly higher in the acamprosate-treated patients (acamprosate, 36.1%; placebo, 23.4%; RB, 1.47; [95% confidence intervals (CI): 1.29-1.69]; p < 0.001). This effect was observed independently of the method used for assigning missing data. The effect sizes in abstinent rates at 3, 6, and 12 months were 1.33, 1.50, and 1.95, respectively. At 12 months, the overall pooled difference in success rates between acamprosate and placebo was 13.3% (95% CI, 7.8-18.7%; number needed to treat, 7.5). Acamprosate also had a modest but significant beneficial effect on retention (6.01%; [95% CI, 2.90-8.82]; p = 0.0106). CONCLUSION: Acamprosate has a significant beneficial effect in enhancing abstinence in recently detoxified, alcohol-dependent individuals.

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PubMed2006

Attenuation of cocaine-induced reinstatement of cocaine conditioned place preference by acamprosate.

Acamprosate (calcium acetylhomotaurinate) is a glutamatergic neuromodulator efficacious at reducing relapse in alcoholic patients. The effect of acamprosate on relapse to other drugs of abuse has received little attention, however, and given increasing evidence that glutamatergic transmission mediates relapse to cocaine-seeking behavior, the purpose of this study was to assess the effects of acamprosate on the reinstatement of a conditioned place preference for cocaine. Mice were conditioned daily with cocaine (15 mg/kg), tested for the establishment of cocaine conditioned place preference, and then retested once weekly to monitor the extinction of the place preference. Following extinction of cocaine conditioned place preference, animals were treated daily with saline or acamprosate (30 or 100 mg/kg) for 3 days, followed by a single injection of cocaine (15 mg/kg) to reinstate conditioned place preference. In mice treated with saline or the low (30 mg/kg) dose of acamprosate, cocaine induced a significant reinstatement of the previously extinguished conditioned place preference; however, this reinstatement was not observed in mice treated with the high (100 mg/kg) dose of acamprosate. These results indicate that acamprosate can attenuate relapse-like behavior in mice and suggest that this compound may be potentially useful in the treatment for cocaine addiction.

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PubMed1999

Effects of acamprosate on memory in healthy young subjects.

OBJECTIVE: Several studies have shown acamprosate (calciumacetylhomotaurinate) to increase abstinence rates in weaned alcoholics. Chronic alcoholics often suffer from cognitive deficits. Since acamprosate appears to interact with N-methyl-D-aspartate (NMDA) receptors, a subclass of glutamate receptors playing an important role in learning and memory processes, this study was performed in order to investigate different cognitive functions during administration of acamprosate. METHOD: A randomized, double-blind, cross-over, placebo-controlled design, involving 12 healthy male volunteers was used. Acamprosate 2 g daily per os or placebo were administered for 7 days respectively, with a wash-out interval of 21 days between phases. Mood and different memory functions (i.e., working memory, delayed recall, recognition tasks) were assessed. RESULTS: It was shown that a dose of acamprosate 2 g/day for 7 days may produce an impairment in delayed free recall. Recognition tasks, short term working memory and mood were not altered. CONCLUSIONS: The present study supports the hypothesis that acamprosate impairs memory functions. This is in keeping with the concept of acamprosate acting as NMDA receptor antagonist. The limitations of the study are discussed.

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PubMed2005

Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action.

Acamprosate is an abstinence-promoting drug widely used in the treatment of alcohol dependence but which has a mechanism of action that has remained obscure for many years. Recently, evidence has emerged that this drug may interact with excitatory glutamatergic neurotransmission in general and as an antagonist of the metabotropic glutamate receptor subtype 5 (mGluR5) in particular. These findings provide, for the first time, a satisfactory, unifying hypothesis that can bring together and explain the diverse neurochemical effects of acamprosate. Glutamic acid is involved in several aspects of alcohol dependence and withdrawal, many of which can be modified by acamprosate. For example, during chronic exposure to alcohol, the glutamatergic system becomes upregulated, leaving the brain exposed to excessive glutamatergic activity when alcohol is abruptly withdrawn. The surge in glutamic acid release that occurs following alcohol withdrawal can be attenuated by acamprosate. The elevated extracellular levels of glutamic acid observed in withdrawal, together with supersensitivity of NMDA receptors, may expose vulnerable neurons to excitotoxicity, possibly contributing to the neuronal loss sometimes observed in chronic alcohol dependence. In vitro studies suggest that the excitotoxicity produced by ethanol can effectively be blocked by acamprosate. Moreover, glutamatergic neurotransmission plays an important role in the acquisition of cue-elicited drinking behaviours, which again can be modulated by acamprosate. In conclusion, the glutamatergic hypothesis of the mechanism of action of acamprosate helps explain many of its effects in human alcohol dependence and points the way to potential new activities, such as neuroprotection, that merit exploration in the clinic.

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PubMed2002

Use of acamprosate and different kinds of psychosocial support in relapse prevention of alcoholism. Results from a non-blind, multicentre study.

OBJECTIVE: To determine abstinence rates and to obtain safety data during the use of integrated therapy with acamprosate and the main established psychotherapeutic intervention programmes in the treatment of alcohol dependence. DESIGN: Non-blind, parallel-group, multicentre, phase IV study. SETTING: Naturalistic setting reflecting the clinical use of acamprosate in outpatient treatment of alcoholics in Germany. PATIENTS: 753 patients meeting the DSM-III-R criteria for alcohol dependence. At study entry, patients had to be abstinent for 1 to 4 weeks, and those who relapsed within the first 14 days of treatment were withdrawn from the study. INTERVENTIONS: All patients received acamprosate 1332 to 1998 mg/day according to bodyweight and were assigned to one of the following treatment groups: individual psychotherapy, group psychotherapy, behavioural therapy, brief intervention or family therapy. The patients were followed for 24 weeks. OUTCOME MEASURES: The principal outcome criterion was the time to the first drink. Secondary outcome measures were cumulative abstinence duration and craving. Adverse events were recorded systematically and classified according to World Health Organization adverse reaction terminology. RESULTS: The mean time to first drink was 81.5 days. 236 (33.5%) patients were continuously abstinent during the study. The discontinuation rate in the study was 49%, and the cumulative abstinence duration was 61%. Abstinence and discontinuation rates in this study were similar to those found in placebo-controlled clinical trials. Craving fell to scores of less than 50 on the Lübecker Craving Scale within 2 weeks of treatment initiation. There were no significant differences between the different psychosocial support treatment arms concerning time to first relapse or abstinence rates. Linear regression analysis showed severity of alcohol dependence according to DSM-III-R criteria to be associated with treatment outcome (p = 0.003). The most common adverse clinical events during the first 2 weeks of treatment were diarrhoea (69 patients), pruritus (37 patients), headache (28 patients) and fatigue (16 patients). Acamprosate was discontinued in nine patients (1%) because of severe adverse events; only two cases were clearly linked to treatment (diarrhoea and dermatitis). One death occurred during the study (status asthmaticus). CONCLUSIONS: Abstinence rates with integrated acamprosate and psychosocial support in a naturalistic setting are similar whatever the psychosocial support used, and similar to those seen in placebo-controlled clinical trials of acamprosate. The safety profile of acamprosate was good.

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PubMedDate not supplied

Effect of the combined administration of ethanol and acamprosate on rabbit EEG.

Central effect of ethyl alcohol and acamprosate is based on similar mechanisms. It is mainly connected with their effect on GABAergic, glutamatergic, serotonergic and opioid transmission. Thus, the question arises whether acamprosate administered together with alcohol increases acute central effects of ethanol. We have studied the effect of joint administration of acamprosate with ethanol in rabbits on EEG results from: frontal cortex, hippocampus and midbrain reticular formation. Acamprosate was applied into the stomach at a single dose of 400 mg kg(-1) or repeated doses of 200 mg kg(-1)/day (for 14 days). Ethanol at the dose of 0.8 g kg(-1) was administered iv 120 min after a single dose of acamprosate, or 4 h after the last dose of the drug. Ethanol caused an increase in the slow frequencies (0.5-4 Hz) in the recording, as well as a marked decrease in the fastest frequencies (13-30 and 30-45 Hz). Acamprosate administered jointly with ethanol increased the effect of ethanol on EEG recording; the amount of the fastest frequencies was decreased. When administered as repeated doses, it enhanced alcohol-related changes in EEG, both within slow and fast frequencies. Consumption of ethanol during acamprosate treatment may lead to intensification of central effects of ethanol.

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PubMedDate not supplied

The European acamprosate trials: conclusions for research and therapy.

In an excellent methodological approach, the European acamprosate study project showed that acamprosate increases sobriety times. In one randomized prospective study (n = 260) comparing acamprosate and placebo, with a 1-year treatment phase and 1-year follow-up phase, the authors found that acamprosate is effective only in Lesch type I and type II patients. To investigate the possible influence of diagnostic subgrouping, we applied the Lesch typology in a co-work with the main researchers of the UK study. The UK results concerning acamprosate's effects in the types do not mirror the Vienna results, but the numbers of type I and type II patients, retrospectively found as included in the UK centers, were too small for any conclusions. The distribution of the types points to the fact that too many type III and IV patients had been included to give acamprosate the chance to be effective. Following our typology and also these studies, we developed special treatment approaches. For relapse prevention studies, the cumulative abstinence duration together with the Lesch typology seems to be promising.

Acamprosate↗
PubMed2006

Effects of treatment with acamprosate on beta-endorphin plasma concentration in humans with high alcohol preference.

Treatment with acamprosate, a compound used for relapse prevention treatment of alcoholism, was recently shown to be associated with increased plasma concentration of beta-endorphin in rats selectively bred for high alcohol preference. The aim of our study was to prove this result in a comparative clinical study with a corresponding design. We studied 51 alcohol dependent patients following alcohol withdrawal during treatment with acamprosate versus placebo for 4 weeks. Data were analyzed for patients with high alcohol preference (HP) and low alcohol preference (LP) by dichotomizing the sample according to median alcohol intake prior to detoxification. In line with pre-clinical data, beta-endorphin plasma concentration in HP patients was significantly lower compared with LP patients. Four weeks of treatment with acamprosate resulted in a significantly increased beta-endorphin plasma concentration compared with placebo and a significant difference in HP patients but not in LP patients. In conclusion, acamprosate seems to modulate the endogenous opioid system. Our data are in accordance with the assumption that the effect of acamprosate on endorphin plasma concentrations is mainly based on the effect in the high preferring subgroup. Since beta-endorphin deficiency was earlier associated with alcohol craving and anxiety during withdrawal, abstinence maintaining effects of acamprosate might at least be partially related with the ability to modulate opioidergic activity especially in the subsample of HP patients with an attenuated opioidergic activity during this state.

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