Acamprosate Group Research Articles

ADVERSE DRUG REACTIONS OF BACLOFEN, NALTREXONE, AND ACAMPROSATE IN PATIENTS HAVING ALCOHOL DEPENDENCE: A CROSS-SECTIONAL PHARMACOVIGILANCE STUDY

Objectives: The research aims to investigate the prevalence and patterns of adverse drug reactions (ADRs), gauge the severity of these reactions, establish causality in ADR cases, and assess the preventability of such adverse reactions. Methods: ADR information was gathered through personal interviews with patients or their relatives. Causality was assessed using the Naranjo algorithm, and a modified Hartwig and Siegel Severity Assessment Scale was used for estimating the severity of ADR. ADRs were grouped into various preventability categories based on the modified Schumock and Thornton criteria. Results: The total number of patients evaluated in the baclofen, naltrexone, and acamprosate groups was 65, 28, and 42, respectively. The most commonly reported adverse events with baclofen were nausea (31.25%), followed by fatigue (18.75%) and headache (12.50%). The majority of patients receiving acamprosate reported nausea (57.14%), followed by diarrhea (28.57%). Patients receiving naltrexone most commonly reported nausea (35.71%), followed by abdominal pain (21.43%) and headache (14.28%). Conclusion: This study shed light on the prevalence, severity, causality, and preventability of ADRs associated with anti-craving agents used to treat patients with alcohol withdrawal syndrome, providing valuable insights into the safety profiles of these medications.

Alkol Bağımlı Sıçanlarda Akamprosat Tedavisinin Kalp Kasılması Üzerine Etkisinin İncelenmesi

Background/ Aim: Chronic alcohol use leads to impaired heart contraction and also causes a direct toxic effect on myocardial function. Acamprosate, which is widely used in alcohol dependence, is not known to have a pharmacological effect on cardiac contraction. Therefore, this study aimed to investigate the effects of acamprosate on the heart muscle.
 Materials and Methods: A total of 32 female Wistar rats were divided four groups as control (10 mg/kg/g saline) group, alcohol (10 mg/kg/g alcohol + 10 mg/kg/g saline) group, acamprosate (200 mg/kg/g) group and alcohol+ acamprosate groups (10 mg/kg/g alcohol + 200 mg/kg/g acamprosate + 10 mg/kg/g saline). Alcoholic rats were scored for alcohol dependence and withdrawal. After that, the rats were sacrificed, respectively and the heart tissue was removed. The amplitude and contraction frequencies of the atrium tissue taken from the heart tissue were measured in the isolated tissue bath. 
 Results: Alcohol dependence and withdrawal symptoms were observed in the Alcohol group and Alcohol+Acamprosate group (p

THE RELATIONSHIP OF ACAMPROSATE AND SMALL INTESTINE IN ALCOHOLIC RATS

ABSTRACT
 Objective: Acamprosate, which is used to reduce alcohol use relapse in alcohol use disorder; It was aimed to evaluate its side effects and its effectiveness in the small intestine.
 Materials and Methods: The related study was carried out on 20.9.2021-25.10.2021. In the study, 32 Wistar Albino female rats were used. Saline at a concentration of 10 mg/kg/g was given to the control group. The alcohol group received 10 mg/kg/g ethanol diluted with 10 mg/kg/g saline. Acamprosate group received 200 mg/kg/g acamprosate diluted with 10 mg/kg/g saline. In the total group, 10 mg/kg/g ethanol was diluted with 10 mg/kg/g saline before being combined with 200 mg/kg/g acamprosate. Alcohol withdrawal symptoms on the 21st day were studied. The small intestinal tissues were hung in the isolated organ wash on the 22nd day.
 Results: Alcohol withdrawal syndrome results from both the alcohol and total groups were significant (p

BPSS Award

Background:Alcohol dependence syndrome is a global illness and anticraving medications are one of its management approaches. Understanding of mechanism of action of anticraving agents in alcohol dependence syndrome (ADS) is limited.Aim:The authors investigated early changes of central glutamate and GABA with Acamprosate and Baclofen among patients with ADS.Methods:Forty patients with ADS were recruited with purposive sampling. At the end of detoxification (CIWA-Ar<10) central glutamate and GABA were measured with magnetic resonance spectroscopy. SADQ, PACS were administered. Either Acamprosate or Baclofen was started with double blind random allocation. After 25 days of starting Baclofen or Acamprosate measures were repeated.Results:Both groups had shown comparable changes in craving, glutamate, and GABA levels. SAD-Q, PACS baseline and CIWA-Ar baseline were negatively corelated with GABA change in Baclofen group raising a speculation that whether Baclofen would be more effective in less severe dependence or vice-versa. In Acamprosate group CIWA-Ar baseline was positively corelated with glutamate change. Baseline glutamate was negatively corelated with glutamate change in both groups but was positively correlated with GABA change in Acamprosate group only speculating that Acamprosate could be more effective than Baclofen in more severe alcohol dependence.Conclusions:Our study has shown comparable changes in Glutamate and GABA at anterior cingulate cortex during early post-detoxification period both for Baclofen and Acamprosate.

A comparative study on the safety and efficacy of naltrexone versus baclofen versus acamprosate in the management of alcohol dependence.

Background:The efficacy of naltrexone, baclofen, and acamprosate in the treatment of alcohol dependence has been successfully established over the past several years. The knowledge about their relative efficacies can facilitate in developing relapse prevention strategies that would give rise to a greater personal and socioeconomic benefits.Aims and Objective:To assess and compare the safety and efficacy profile of naltrexone, baclofen, and acamprosate in the treatment of alcohol dependence. In addition to this, the pattern of relapse and attitude of patients toward the treatment were also assessed.Materials and Methods:This was a prospective study carried out at a tertiary care center. It comprised of thirty alcohol-dependent patients each assigned to naltrexone, baclofen, and acamprosate group after detoxification. The patients were assessed for craving, relapse risk, and medication adherence using the respective scales and questionnaires.Results:In terms of Obsessive Compulsive Drinking Scale score decline, the decline seen in the naltrexone group (26.72 ± 13.05) was maximum, followed by baclofen and acamprosate. In terms of decreasing Advance Warning of Relapse (AWARE) questionnaire score, again naltrexone was most effective, with the maximum decline in AWARE score (64.72 ± 45.65), followed by baclofen and acamprosate. The attitude toward treatment with all the three medications was positive, as per the Hogan Drug Attitude Inventory score.Conclusion:Naltrexone was most effective in decreasing craving and drinking behavior. Baclofen showed best tolerability in terms of liver function tests and least number of side effects reported. Naltrexone group reported the least number of relapses but maximum number of side effects. Acamprosate group had the maximum dropout rate.

Insomnia in Alcohol-Dependent Patients: Prevalence, Risk Factors and Acamprosate Effect: An Individual Patient Data Meta-Analysis.

The prevalence of insomnia ranges from 36% to 91% in alcohol-dependent patients and may persist after alcohol withdrawal. Acamprosate has been shown to decrease insomnia in abstinent patients. Based on a large clinical trial database, the aim of the present study is to assess the efficacy of acamprosate in reducing insomnia, and if indeed it does reduce insomnia, to better understand its action mechanism. The aim of the study is to confirm the efficacy of acamprosate to reduce insomnia using an individual patient data meta-analysis. Twelve studies were found including 3508 patients. After a 6-month follow-up, the mean insomnia decrease over baseline was -26% and -45% for the placebo and acamprosate groups, respectively (P < 0.001). An individual patient data meta-analysis selected all the randomized trials of acamprosate in which insomnia was documented. Our main endpoint was insomnia change after a 6-month follow-up, measured by the validated Short Sleep Index (SSI) derived from the Hamilton Depression and Anxiety Scale. The meta-analysis was conducted using a two-level multilevel (patient/trial) mixed model with random treatment effect, random study effect and adjusting for baseline severity covariates. Twelve studies were found including 3508 patients, 59.8% of whom were suffering from insomnia (95% CI 58.1-61.4). Psychiatric history, severe addiction, living alone and abnormal gamma-GT levels were found to be the risk factors of insomnia. After 6 months, the mean SSI decrease over baseline was -26% and -45% for placebo and acamprosate, respectively (treatment effect = 19%, 12.5-25.5; P < 0.001). By using a univariate mediation model, we found that the mediating effect of abstinence on insomnia accounted for 55.7% of the overall effect of acamprosate on insomnia reduction. Insomnia is prevalent among alcohol-dependent patients. It decreases spontaneously with abstinence but more frequently with acamprosate treatment.

Calcium as a treatment option for alcohol dependence

In the last couple of decades anti-craving drugs have been developed. Acamprosate was described as an effective treatment option to support alcohol abstinence with a low side effect profile. Moreover its molecular mode of action is highly controversial. Recently, calcium salt was described to be the active part of Acamprosate.Using a clinical sample of placebo (n = 10) vs. Acamprosate-treated (n = 19) abstinent alcohol-dependent patients, we measured calcium plasma concentrations after the 1st, 2nd and 3rd month after the treatment commenced. Before treatment, the same physiological calcium concentration of about 2.4 mmol/l was found in both groups respectively. We found significant correlations in the Acamprosate group while no correlations in the placebo group were observed.The very well regulated extracellular calcium serum concentration seems to get out of balance in association with the severity of alcohol dependence in inpatients during withdrawal.Accordingly, in another clinical sample (n = 57) we found a negative correlation between calcium serum concentration and craving (r2= 0.125; P = 0.011) on day 1 of detoxification. The measurement of craving was carried out by a self-rating scale, the Obsessive Compulsive Drinking Scale (OCDS). Furthermore a low calcium level correlated with high breathalyser readings and the number of alcohol inpatient detoxification's.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Calcium for the treatment of alcohol-dependence

Using a clinical sample of placebo vs. acamprosate-treated abstinent alcohol-dependent patients, we measured calcium plasma concentrations. Before treatment, the same physiological calcium concentration of about 2.4 mmol/l were found in the placebo and acamprosate group. Additionally, blood was drawn after 1, 2 and 3 months of treatment. Although calcium levels are extremely tightly controlled by the kidneys and parathyroid hormone and are more or less constant in each individual. We found tendency (p < 0.1) of enhanced calcium plasma levels in acamprosate vs. placebo treated patients. When correlating the primary efficacy parameters of first drink (rho = 0.64; p < 0.01), severe relapse (rho = 0.43; p = 0.057) and cumulative abstinence (rho = 0.57; p < 0.01) with calcium plasma levels, we found significant correlations in the acamprosate group. We did not find any correlation in the placebo group. Furthermore deviation from the calcium plasma concentration in inpatient alcohol dependent patients during withdrawal seems to be associated with severity of alcohol dependence and craving. This study was supported by DFG

Correlates of Baclofen Effectiveness in Alcohol Dependence

Alcohol dependence is a global concern. Baclofen has shown promise as an anti-craving agent but its efficiency remains to be settled. We reviewed 549 male cases diagnosed with alcohol dependence who received Acamprosate (201) or Baclofen (348). ‘Time to first drink’ was compared between two groups and multiple regression analysis was done in baclofen group to identify correlates of effectiveness. There was a significant difference in outcome measure between Baclofen (M = 4.44, SD = 3.75) and Acamprosate group (M = 3.73, SD = 2.19); t (547) = 2.45, P = 0.01. Initial regression analysis with six predictor variables (average daily alcohol units, current age, age at onset of dependence, family history, duration of dependence and dose of baclofen in mg/day) showed significant correlation of outcome variable with only two predictor variables — dose of baclofen and average daily intake. Using the hierarchical method it was found that ‘dose of baclofen’ and ‘average alcohol intake’ explain a significant amount of variance in ‘time to first drink’. [F (1, 345) = 182.8, P < 0.001, R2 = 0.52, R2adjusted = 0.51]. This information can be used to select patients in long term longitudinal studies and may explain variable results seen in clinical trials of baclofen done earlier.

The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta-analysis.

To determine the efficacy of acamprosate and naltrexone in the treatment of those who are alcohol-dependent in reducing lapse/relapse to alcohol consumption and treatment discontinuation, and to examine whether a proportion of the variance in study outcome can be explained by the country in which the trials have taken place. A systematic review and meta-analysis of randomized controlled trials published before September 2013 was conducted. The primary outcome measures were the efficacy of acamprosate or naltrexone in reducing lapse/relapse compared to placebo in the treatment of alcohol dependence and treatment discontinuation. Twenty-two randomized controlled trials (RCTs) of the efficacy of acamprosate met inclusion criteria for the meta-analysis, with a total of 2649 participants in the acamprosate group and 2587 in the placebo group. Twenty-seven RCTs of the efficacy of naltrexone met inclusion criteria for the meta-analysis, with a total of 2253 participants in the naltrexone group and 1946 in the placebo group. A random-effects model using a Mantel-Haenszel method was applied to conduct the meta-analysis. Variance in study outcomes was explored using subgroup analysis of Europe versus the rest of the world (ROW). The risk of returning to any drinking at 6 months was significantly lower for acamprosate [risk ratio (RR) = 0.83, 95% confidence interval (CI) = 0.78-0.89]. There was little difference in the risk of participants discontinuing treatment for any reason (RR = 0.91, 95% CI = 0.83-1.00) or due to adverse events (RR = 1.30, 95% CI = 0.96-1.75) for the acamprosate compared to placebo groups. The risk of individuals returning to any drinking at approximately 3 months was reduced significantly for the naltrexone group (RR = 0.92, 95% CI = 0.86-1.00), as was the risk of individuals relapsing to heavy drinking at 3 months (RR = 0.85, 95% CI = 0.78-0.93). There was no significant difference between naltrexone and placebo for the risk of individuals discontinuing treatment for any reason (RR = 0.94, 95% CI = 0.84-1.05). There was a significantly greater risk of participants in the naltrexone group discontinuing treatment due to adverse events compared to placebo (RR = 1.72, 95% CI = 1.10-2.70). Subgroup analysis by country (Europe versus ROW) revealed no difference in risk between acamprosate and placebo for the outcomes returning to any drinking at 6 months and discontinuing treatment due to adverse events. For the outcome discontinuation of treatment for any reason, there was a significant difference in RR between Europe and the ROW (χ(2) = 11.65, P <0.001) for acamprosate. Acamprosate was associated with a reduction in risk of discontinuing treatment for Europe (RR = 0.86, 95% CI = 0.79-0.95), but an increase in risk of discontinuing treatment for ROW (RR = 1.23, 95% CI = 1.03-1.48). Both acamprosate and naltrexone appear to reduce the risk of individuals returning to drinking alcohol in those who are alcohol-dependent. The country in which a randomized control trial (RCT) for the efficacy of acamprosate and naltrexone is completed does not appear to explain the variance in trial outcomes for returning to drinking alcohol or discontinuing drinking due to adverse effects. However, the country in which the RCT of acamprosate are completed may be important for explaining the variance between studies for the outcome 'discontinuing treatment for any reason'.

Efficacy of acamprosate for the treatment of alcohol dependence long after recovery from withdrawal syndrome: a randomized, double-blind, placebo-controlled study conducted in Japan (Sunrise Study).

To undertake a double-blind, randomized, placebo-controlled trial to examine the efficacy of acamprosate in maintaining complete abstinence in Japanese patients with alcohol dependence. We enrolled 327 patients with ICD-10-defined alcohol dependence and randomly assigned them to treatment with either acamprosate (1,998 mg/d orally) or placebo for 24 weeks. The primary endpoint was complete abstinence after 24 weeks of administration. The study was performed at 34 medical institutions between 2009 and 2011. The acamprosate group demonstrated significantly superior efficacy versus the placebo group on the primary endpoint: the proportion maintaining complete abstinence in the acamprosate group was 47.2% (77/163 subjects), compared with 36.0% (59/164 subjects) in the placebo group (P = .039). The difference in complete abstinence rates between the 2 groups was 11.3% (95% CI, 0.6%-21.9%). Acamprosate is superior to placebo in maintaining abstinence in Japanese patients with alcohol dependence. These findings concur with 11 randomized, blinded, placebo-controlled clinical trials conducted in Europe. This study was designed to reflect clinical practice in Japan and is therefore a meaningful addition to the available evidence in this field. JapicCTI identifier: 090694.

SY18-3 * EFFICACY OF ACAMPROSATE FOR THE TREATMENT OF ALCOHOL DEPENDENCE LONG AFTER RECOVERY FROM WITHDRAWAL SYNDROME: AN RCT CONDUCTED IN JAPAN

Objective. To undertake a double blind, randomized, placebo controlled trial to examine the efficacy of acamprosate in maintaining complete abstinence in Japanese patients with alcohol dependence. Methods. We enrolled 327 patients with alcohol dependence that met the criteria described in ICD-10, and randomly assigned them to either treatment with acamprosate (1,998 mg/day orally) or placebo for 24 weeks. The primary endpoint was complete abstinence after 24 weeks of administration. The study was performed at 34 medical institutions between 2009 and 2011. Results. The acamprosate group demonstrated significantly superior efficacy than the placebo group in the primary endpoint: the proportion maintaining complete abstinence in the acamprosate group was 47.2% (77/163 subjects), compared with 36.0% (59/164 subjects) in the placebo group (p = 0.039). The difference in complete abstinence rates between the two groups was 11.3% (0.6-21.9%, 95% CI). Conclusion. Acamprosate is superior to placebo in maintaining abstinence in Japanese patients with alcohol dependence. These findings concur with 11 randomized, blinded, placebo-controlled clinical trials conducted in Europe. This study was designed to reflect clinical practice in Japan, and is therefore a meaningful addition to the available evidence in this field.

A Randomized, Controlled, Pilot Study of Acamprosate Added to Escitalopram in Adults With Major Depressive Disorder and Alcohol Use Disorder

We sought to examine the efficacy and safety of acamprosate augmentation of escitalopram in patients with concurrent major depressive disorder (MDD) and alcohol use disorders. Twenty-three adults (43% female; mean ± SD age, 46 ± 14 years) were enrolled and received 12 weeks of treatment with psychosocial support; escitalopram, 10 to 30 mg/d; and either acamprosate, 2000 mg/d (n = 12), or identical placebo (n = 11). Outcomes included change in clinician ratings of depressive symptoms, MDD response and remission rates, changes in frequency and intensity of alcohol use, retention rates, and adverse events. Twelve subjects (acamprosate, n = 7; placebo, n = 5) completed the study. There was significant mean reduction in ratings of depressive symptoms from baseline in both treatment arms (P < 0.05), with no significant difference between the groups. Those in the acamprosate group had a 50% MDD response rate and a 42% remission rate, whereas those in the placebo arm had a 36% response and remission rate (not significant). Those assigned to acamprosate had significant reduction in number of drinks per week and drinks per month during the trial, whereas those assigned to placebo demonstrated no significant change in any alcohol use parameter, but the between-group difference was not significant. There were no significant associations between change in depressive symptoms and change in alcohol use. Attrition rates did not differ significantly between the 2 arms. Acamprosate added to escitalopram in adults with MDD and alcohol use disorders was associated with reduction in the frequency of alcohol use. The present study was not powered to detect superiority versus placebo. Further study in a larger sample is warranted.

Acamprosate in the treatment of alcoholism: a budget impact analysis for the National Health Service in Italy

ObjectiveAlcohol dependence is a common condition associated with high direct and indirect health care costs. The purpose of this analysis was to estimate the economic consequences of acamprosate used as adjuvant therapy in the treatment of alcoholism, defining a budget impact analysis (BIA) from the point of view of the Italian National Health Service (NHS).MethodsWe developed a model of disease evolution related to alcoholism using data from the PRAMA study. The hypothetical population included in the decision model was obtained from data from the Ministry of Health. We compared the following treatment strategies: no treatment, standard care (psychotherapy), sodium oxybate (sodium salt-4-hydroxybutyric acid), and acamprosate. The time horizon of the model was 10 years. The costs were evaluated from the NHS perspective.ResultsWe simulated the path for 69,348 patients treated at the outpatient clinics of the Addiction Services (SerT), and 38,911 patients discharged from hospital. Patients in the acamprosate group had lower alcohol-related events, with a reduction of the total cost. The BIA shows that the increase in the use of acamprosate was associated with a progressive decrease of total costs, calculated as the sum of the diagnosis-related groups (DRG), rehabilitation, and drug costs. The increasing use of acamprosate instead of standard care and sodium oxybate would generate cost savings up to over €6 million over 10 years of simulation.ConclusionThe estimates in the model are based on hypothetical situations; the assumptions of the model as well as their specific impact on treatment effect estimations and clinical implications should be validated in real life. Public health care authorities would benefit from mathematical models designed to estimate the future burden of alcohol dependence together with the impact of treatment and the potential to reduce the incidence and progression of this condition, and the costs of its complications.

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

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 randomized 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. 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. 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). 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.

S15 * ESBRA/ISBRA JOINT SYMPOSIUM: IMAGING IN ALCOHOL RESEARCH * S15.1 * THE ROLE OF FUNCTIONAL NEUROIMAGING IN THE CHOICE OF TREATMENT FOR ALCOHOLICS

S15 * ESBRA/ISBRA JOINT SYMPOSIUM: IMAGING IN ALCOHOL RESEARCH * S15.1 * THE ROLE OF FUNCTIONAL NEUROIMAGING IN THE CHOICE OF TREATMENT FOR ALCOHOLICS

Urinary Ethyl Glucuronide and Ethyl Sulfate Testing for Recent Drinking in Alcohol-Dependent Outpatients Treated with Acamprosate or Placebo

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are sensitive and specific biomarkers for recent alcohol ingestion. This study compared urinary EtG and EtS measurement with self-reports for detection of prior drinking in alcohol-dependent outpatients treated with the anti-craving medication acamprosate or placebo. Alcohol-dependent outpatients (26 women, 30 men) were randomized to 21 days of oral acamprosate (2 g/day) or placebo treatment in a double-blind design. They were instructed to refrain from drinking during the study. Return visits to the ward for blood and urine sampling and filling out questionnaires were made on Day 7, 14 (urine sample optional) and 22 (urine sample mandatory). EtG and EtS were determined by liquid chromatography-mass spectrometry. On the first day (Day 0), 72% of all patients (acamprosate 65%, placebo 78%) tested positive for recent drinking according to urinary EtG (reporting limit ≥ 0.5 mg/l) and EtS (≥ 0.1 mg/l). On the final day (Day 22), the frequency of positive tests was significantly reduced to 30% in the acamprosate group (P = 0.0374) and 33% for placebo (P = 0.0050). However, there was no difference between the treatment groups. When both groups were combined, the EtG (P = 0.025) and EtS (P = 0.015) concentrations were lower on the final day. Altogether, EtG and EtS were detected in 76 of 156 (49%) urine samples. When drinking in the day before sampling was admitted, 93% of urines tested positive; when drinking was denied, still 28% of the samples were positive. These results confirmed the value of urinary EtG and EtS as reliable indicators of recent drinking during outpatient treatment of persons with alcohol-related problems, and as objective outcome measures when evaluating new alcohol treatment strategies and pharmacotherapies.

Predictors of clinical trial dropout in individuals with co-occurring bipolar disorder and alcohol dependence

BackgroundIndividuals with co-occurring bipolar disorder and alcohol dependence have particularly low rates of retention in clinical trials. Past research has identified a variety of factors associated with dropout in this population, but few have been replicated. The present study investigated the ability of several baseline variables to predict clinical trial dropout in a sample of individuals with co-morbid bipolar and alcohol use disorders. MethodsDemographics, psychiatric diagnoses, recent alcohol use, mood pathology, and risk taking behavior (measured with the Balloon Analogue Risk Task) were evaluated as predictors of dropout from a randomized clinical trial of acamprosate for individuals with co-morbid bipolar and alcohol use disorders (n=30) using stepwise logistic regression. ResultsRisk taking behavior was the only significant predictor of dropout in the present study (OR=1.44, p=0.03); opiate dependence marginally predicted dropout as well (OR=13.46, p=0.08). A model consisting of these predictors, as well as acamprosate group status (p=0.13), provided excellent prediction of dropout (i.e., area under the ROC curve=0.94; R2=0.53). ConclusionsGiven the robust relationship between risk taking and dropout in the present study, the Balloon Analogue Risk Task may represent a valuable tool for researchers to predict who will drop out of clinical trials for comorbid bipolar and substance use disorders.

Treatment With Acamprosate in Patients With Schizophrenia Spectrum Disorders and Comorbid Alcohol Dependence

Objective: Alcohol use disorders and schizophrenia frequently co-occur with rates higher than in the general population. There is no consensus on the best treatment for patients with these comorbid conditions. Several clinical trials have shown that acamprosate is superior to placebo in reducing drinking and is particularly effective in sustaining abstinence. No study to date has examined the efficacy of acamprosate in patients with alcohol dependence and comorbid schizophrenia. The aims of this study are to assess the efficacy of acamprosate when compared to placebo in reducing drinking and to examine its effects on schizophrenic symptoms. Methods: This was a double-blind, randomized, 12-week treatment trial of acamprosate versus placebo. Twenty-three recently abstinent patients with diagnosed alcohol dependence and comorbid schizophrenia, schizoaffective disorder, or psychosis not otherwise specified were included in this study. Results: All participants significantly decreased their drinking during medication treatment, although acamprosate was not superior to placebo in increasing consecutive days of abstinence. There was a significant difference favoring the acamprosate group on obsessive thoughts of drinking but no significant group X time interaction. Overall, medication treatment significantly reduced positive symptoms of schizophrenia, but there were no group differences. Conclusions: Acamprosate was not more effective than placebo in reducing drinking or symptoms of schizophrenia. It can be safely used in patients with alcohol dependence and comorbid schizophrenia spectrum disorders.

Acamprosate in the treatment of binge eating disorder: A placebo‐controlled trial

To assess preliminarily the effectiveness of acamprosate in binge eating disorder (BED). In this 10-week, randomized, placebo-controlled, flexible dose trial, 40 outpatients with BED received acamprosate (N = 20) or placebo (N = 20). The primary outcome measure was binge eating episode frequency. While acamprosate was not associated with a significantly greater rate of reduction in binge eating episode frequency or any other measure in the primary longitudinal analysis, in the endpoint analysis it was associated with statistically significant improvements in binge day frequency and measures of obsessive-compulsiveness of binge eating, food craving, and quality of life. Among completers, weight and BMI decreased slightly in the acamprosate group but increased in the placebo group. Although acamprosate did not separate from placebo on any outcome variable in the longitudinal analysis, results of the endpoint and completer analyses suggest the drug may have some utility in BED.