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Introduction: The aim of the present study was to examine for the first time the factorial, construct, and predictive validity of the motivation for treatment (MfT) scale in a cohort of patients undergoing inpatient-qualified alcohol withdrawal treatment with the goal of referring patients to further treatment. The MfT scale has previously been evaluated in different settings of substance abuse treatment, revealing factorial ambiguity. To the best of our knowledge, the present study is the first study that conducted comprehensive factor analyses versus separate analyses of the factors conducted in prior studies in order to clarify the aforementioned factorial ambiguity., Methods: A total of 249 patients (mean age 45.2 years (SD = 10.3); 34.4% females) with alcohol dependence were assessed. Data were obtained from four inpatient clinics specialized in qualified alcohol withdrawal treatment in Germany. First, confirmatory factor analyses were carried out to examine the fit of the four models discussed in the literature. Second, an exploratory factor analysis was conducted. Correlations of the new factors with other motivational constructs and referral to a subsequent treatment were investigated as measures of construct and predictive validity., Results: None of the four models showed an acceptable fit to the data in confirmatory analyses. The exploratory analysis suggested to eliminate seven items because of inappropriate factor loadings and resulted in a shortened MfT scale, which consists of three factors based on 17 items. For the latent variables "problem recognition," "desire for help," and "treatment readiness," satisfactory composite reliability was found with 0.82, 0.80, and 0.78, respectively. Evidence for predictive validity was found in the correlation between "treatment readiness" and referral to a subsequent treatment., Discussion/conclusion: The new shortened MfT scale exhibited remarkable parsimony, which is desirable in settings such as withdrawal treatment, where patients frequently are cognitively or physically impaired. Despite its briefness, construct and predictive validity were better than in the original version of the MfT scale. The factorial validity of the suggested scale needs to be corroborated in further research., (© 2023 S. Karger AG, Basel.)

Background: In the implementation of placement matching guidelines, feasibility has been concerned in previous research. Objectives of this process evaluation were to investigate whether the patient-centered matching guidelines (PCPM) are consistently applied in referral decision-making from an inpatient qualified withdrawal program to a level of care in aftercare, which factors affect whether patients actually receive matched aftercare according to PCPM, and whether its use is feasible and accepted by clinic staff., Methods: The study was conducted as process evaluation within an exploratory randomized controlled trial in four German psychiatric clinics offering a 7-to-21 day qualified withdrawal program for patients suffering from alcohol dependence, and with measurements taken during detoxification treatment and six months after the initial assessment. PCPM were used with patients in the intervention group by feeding back to them a recommendation for a level of care in aftercare that had been calculated from Measurements in the Addictions for Triage and Evaluation (MATE) and discussed with the staff on the treatment unit. As measurements, The MATE, the Client Socio-Demographic and Service Receipt Inventory-European Version, a documentation form, the Control Preference Scale, and the Motivation for Treatment Scale were administered. A workshop for the staff at the participating trial sites was conducted after data collection was finished., Results: Among 250 patients participating in the study, 165 were interviewed at follow-up, and 125 had received aftercare. Although consistency in the application of PCPM was moderate to substantial within the qualified withdrawal program (Cohen's kappa ≥ .41), it was fair from discharge to follow-up. In multifactorial multinomial regression, the number of foregoing substance abuse treatments predicted whether patients received more likely undermatched (Odds Ratio=1.27; p=.018) or overmatched (Odds Ratio=0.78; p=.054) treatment. While the implementation process during the study was evaluated critically by the staff, they stated a potential of quality assurance, more transparency and patient-centeredness in the use of PCPM., Conclusions: While the use of PCPM has the potential to enhance the quality of referral decision making within treatment, it may not be sufficient to determine referral decisions for aftercare., Trial Registration: German Clinical Trials Register DRKS00005035 . Registered 03/06/2013., (© 2022. The Author(s).)

Acamprosate and naltrexone are medications of proven efficacy in the treatment of alcohol dependence. In order to investigate the prescription of these drugs in outpatient routine treatment in Germany (frequency of prescription, duration, medical specialty of prescribing physician), data of a large statutory health insurance were analyzed. Persons were included who were discharged from inpatient treatment with an alcohol-related disorder among their diagnoses during a one year observation period and with no diagnosed additional substance-related disorder (apart from nicotine- and cannabis-related disorders). Thus 12.958 patients were identified (mainly male, 77.9%; at average 51.4 years [+/-12.7] of age). 44.3% of these patients were treated in a psychiatric hospital, the remaining patients in hospitals of other specialties (e. g. 9.2% in departments of surgery). During an observation period of 6 months after discharge, acamprosate or naltrexone were prescribed at least once to 98 persons (0.76% of 12.958 patients; acamprosate n=80, 0.62%; naltrexone n=18, 0.14%). 16 (0.12%) patients were prescribed acamprosate or naltrexone for more than 3 months. Half of the prescriptions were issued by general practitioners. Possible reasons for this under-prescription are lack of knowledge about the drug treatment of alcohol dependence outside of addiction psychiatry, neglect of biological aspects (including medication) regarding etiology and treatment of substance-related disorders, and stigma of patients with substance-related disorders., Competing Interests: Dr. Scherbaum reports personal fees from AbbVie, personal fees from Indivior, personal fees from Sanofi-Aventis, personal fees from Mundipharma during the past 3 years. U. Kirchhof, U. Bonnet, G. Stammen and R. Holzbach have nothing to declare., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Placement matching guidelines are promising means to optimize patient-centered care and to match patients' treatment needs. Despite considerable research regarding placement matching approaches to optimize alcohol abuse treatment, findings are inconclusive., Objectives: To investigate whether the use of patient-centered placement matching (PCPM) guidelines is more effective in reducing heavy drinking and costs 6 months after discharge from an inpatient alcohol withdrawal treatment compared to usual referral to aftercare. Secondary aims were to investigate whether age, gender, trial site or level of care (LOC) are moderators of efficacy and whether patients who were actually referred to the recommended LOC had better treatment outcomes compared to patients who were treated under- or overmatched., Methods: Design. Exploratory randomized controlled trial with measurements during withdrawal treatment and 6 months after initial assessment., Setting: Four German psychiatric clinics offering a 7-21 day inpatient qualified withdrawal program for patients suffering from alcohol dependence., Participants: From 1,927 patients who had a primary diagnosis of alcohol dependence and did not have organized aftercare when entering withdrawal treatment, 299 were invited to participate. Of those, 250 were randomized to the intervention group (IG, n = 123) or the control group (CG, n = 127)., Intervention: The PCPM were applied to patients of the IG by feeding back a recommendation to a LOC for aftercare that was calculated from the Measurements in the Addictions for Triage and Evaluation (MATE) and discussed with the staff of the treatment unit. Patients of the CG received a general feedback regarding their MATE interview on request., Measurements: The MATE, the Client Socio-Demographic and Service Receipt Inventory--European Version and the MATE-Outcomes were administered. Data were analyzed using generalized linear models., Results: In the intention-to-treat analysis, there were no significant differences between IG and CG regarding days of heavy drinking (incident risk ratio [IRR] 1.09; p = 0.640), direct (IRR 1.06; p = 0.779), indirect (IRR 0.77; p = 0.392) and total costs (IRR 0.89; p = 0.496). Furthermore, none of the investigated moderator variables affected statistically significant drinking or cost-related primary outcomes. Regardless of group allocation, patients who received matched aftercare reported significantly fewer days of heavy drinking than undermatched patients (IRR 2.09; p = 0.004). For patients who were overmatched, direct costs were significantly higher (IRR 1.79; p = 0.024), but with no additional effects on alcohol consumption compared to matched patients., Conclusions: While the use of PCPM failed to affect the actual referral to aftercare, our findings suggest that treating patients on the recommended LOC may have the potential to reduce days of heavy drinking compared to undertreatment and costs compared to overtreatment., (© 2020 S. Karger AG, Basel.)

Importance: According to recent studies, only a small proportion of alcoholics in the system for addiction treatment receive expedited treatment [Rehm et al.: Sucht 2014;60:93-105] and that those who are untreated are at risk of harmful and dependent alcohol consumption. This is associated with significantly negative effects on morbidity, mortality, and quality of life [Kraus et al.: Sucht 2010;56:337-347]. As a result, not only individuals and their environment suffer but there is also a health economic impact., Objective: How often do patients with a primary or secondary diagnosis of alcohol dependence who have been discharged from inpatient treatment receive anticraving medication in the follow-up period of 6 months?, Design, Setting, and Participants: Based on data from a statutory health insurance in Germany, 12,958 patients were investigated regarding alcohol dependence, rates for readmission to hospital, and prescription of anticraving drugs. In addition, outpatient and inpatient treatment costs were calculated. Main Outcomes and Measures: There will be an examination of how often anticraving medications are prescribed and what the economic consequences are., Results: Two hundred and eighty-eight (2.22%) patients received anticraving medication, 98 (0.76%) in the first 6 months after inpatient treatment. Fifty-nine of the 288 patients were monitored with a pre- and postcomparison over a 90-day period. Inpatient treatment fell from 0.83 times (±1.10) during the 3 months afterward to 0.79 (±1.01). On average, the duration of an inpatient stay before anticraving treatment (n = 29) was 17.34 days (±14.37), with an average cost of EUR 4,142.70 (±2,721.28). Among the anticraving treatment group, this fell to 14.03 days (±9.96) with an average cost of EUR 3,685.43 (±2,307.67). Overall, the average outpatient and inpatient treatment costs dropped from EUR 1,533.88 before treatment to EUR 1,462.76 after treatment. If this is extrapolated to the whole group, it leads to between EUR 921,500 and EUR 6.6 million saving for a health insurance company., Conclusion: Anticraving medications are hardly ever prescribed. Their routine use could reduce hospital readmission rates and save on health-care costs., (© 2019 S. Karger AG, Basel.)

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10 -13 ) and African ancestries (rs2066702; P = 2.2 × 10 -9 ). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Aims: Shared decision making (SDM) is increasingly demanded in medical decision making. SDM acknowledges patients' role preferences in decision making processes. There has been limited research on SDM and role preferences in substance use disorders; results are promising. Aim of this study was to investigate role preferences of patients with alcohol use disorders (AUD), and to identify predictors of these preferences., Method: Cross-sectional data collected from June 2013 to May 2014 in four detoxification wards in Germany during a randomised controlled trial (RCT, Registration Code 01GY1114) was analysed. Of the 250 patients with AUD who were included in the RCT, data from 242 patients [65% male; mean age = 45.2 years (sd = 10.3)] were analysed. Participants' role preferences were assessed with the Control Preference Scale. Potential correlates were drawn from instruments used in the RCT; multinomial logistic regression was used., Results: 90% (n = 217) of the AUD patients preferred an active or shared role in decision-making, 10% (n = 25) preferred a passive role. Patients' desire for help was associated with their role preference (OR = 3.087, p = .05). The model's goodness of fit was Nagelkerke's R 2  = 0.153 [χ 2 (24) = 25.206, p = .395]., Conclusions: Patients' preference for an active role in decision-making underscores the importance of involving patients in their treatment planning. Patients' desire for help seems to be an important determinant of paternalistic decision making. However, further research is needed to determine whether patients' role preferences are related to their behavior during their treatment referral and recovery., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Heavy alcohol use can cause somatic and mental diseases, affects patients' social life and is associated with social isolation, unemployment and reduced quality of life. Therefore, societal costs of alcohol dependence are expected to be high. The aim of this study was to estimate excess costs of patients with alcohol dependence diagnosed using the Diagnostic and Statistical Manual of Mental Disorders , 4th Edition criteria compared with individuals without alcohol dependence in Germany., Design: In a secondary analysis, baseline data of patients with alcohol dependence enrolled in a randomised controlled trial (German Clinical Trials Register DRS00005035) were compared with data collected via a telephone survey from individuals without alcohol dependence and that had been matched by entropy balancing. Health service use was evaluated retrospectively for a 6-month period., Settings: Four German psychiatric university clinics (patients with alcohol dependence) and the German general adult population (individuals without alcohol dependence)., Participants: n=236 adult patients with alcohol dependence and n=4687 adult individuals without alcohol dependence., Primary and Secondary Outcome Measures: The excess costs of health service use, absenteeism and unemployment of patients with alcohol dependence were calculated and compared with individuals without alcohol dependence. In subgroup analyses, the associations between excess cost and gender, comorbidities and the duration of disease were investigated., Results: Total 6-month excess costs of €11 839 (95% CI €11 529 to €12 147) were caused by direct excess costs of €4349 (95% CI €4129 to €4566) and indirect costs of €7490 (95% CI €5124 to €9856). In particular, costs of inpatient treatment, formal long-term care, absenteeism and unemployment were high., Conclusions: Alcohol dependence causes substantial direct and indirect excess costs. Cost-effective interventions to prevent and treat alcohol dependence are urgently needed., Trial Registration Number: DRKS00005035., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The clinical comorbidity of alcohol dependence (AD) and major depressive disorder (MDD) is well established, whereas genetic factors influencing co-occurrence remain unclear. A recent study using polygenic risk scores (PRS) calculated based on the first-wave Psychiatric Genomics Consortium MDD meta-analysis (PGC-MDD1) suggests a modest shared genetic contribution to MDD and AD. Using a (~10 fold) larger discovery sample, we calculated PRS based on the second wave (PGC-MDD2) of results, in a severe AD case–control target sample. We found significant associations between AD disease status and MDD-PRS derived from both PGC-MDD2 (most informative P-threshold=1.0, P=0.00063, R2=0.533%) and PGC-MDD1 (P-threshold=0.2, P=0.00014, R2=0.663%) meta-analyses; the larger discovery sample did not yield additional predictive power. In contrast, calculating PRS in a MDD target sample yielded increased power when using PGC-MDD2 (P-threshold=1.0, P=0.000038, R2=1.34%) versus PGC-MDD1 (P-threshold=1.0, P=0.0013, R2=0.81%). Furthermore, when calculating PGC-MDD2 PRS in a subsample of patients with AD recruited explicitly excluding comorbid MDD, significant associations were still found (n=331; P-threshold=1.0, P=0.042, R2=0.398%). Meanwhile, in the subset of patients in which MDD was not the explicit exclusion criteria, PRS predicted more variance (n=999; P-threshold=1.0, P=0.0003, R2=0.693%). Our findings replicate the reported genetic overlap between AD and MDD and also suggest the need for improved, rigorous phenotyping to identify true shared cross-disorder genetic factors. Larger target samples are needed to reduce noise and take advantage of increasing discovery sample size.

Background: The cognitive behavioral therapy has been extensively investigated to assess relapse prevention rates in patients with alcohol dependence. In contrast, only little is known regarding the effectiveness of psychoanalytical psychotherapy in relapse prevention, although this treatment is widely used and especially so in Germany. The aim of this quasi-randomized study was to compare the effectiveness of these two group treatments' approaches under the condition of routine outpatient treatment in a non-university hospital., Methods: After inpatient detoxification, patients with alcohol dependence were allocated either to combined behavioral intervention (CBI) or to psychoanalytic-interactional therapy (PIT). The group treatment was carried out weekly over a period of six months. Also, the clinical care package included both individual treatment sessions (e.g. every 4-6 weeks) and abstinence supporting medication. The main outcome criteria included retention rates and frequency of alcohol relapse., Results: Some 215 patients (mean age 49.6 years [standard deviation, 10], 56.7% males, with a mean duration of alcohol dependence of 16.5 years [range: 1-50 years]) were included in the study. Overall, CBI clients showed a retention rate of 66.7%, compared to 81.8% for PIT clients (p =.008). An intention-to-treat analysis of alcohol relapses showed a significant difference between PIT and CBI groups (PIT: 33.6%; CBI: 49.5%; p =.018). There were no statistically significant differences between the 2 groups in terms of prescription rates of disulfiram, naltrexone or acamprosate., Conclusions: Notwithstanding the study limitations, PIT seemed here to be at least as effective as CBI in terms of retention and relapse prevention rates' levels.

Background: Understanding the biological underpinnings of relapse in alcohol dependency is a major issue in addiction research. Based on recent evidence regarding the relevance of occipital visual evoked response potentials (ERPs) in addiction research, and its significance for relapse research, we assessed occipital ERPs to alcohol- and non-alcohol-related stimuli in recently detoxified patients and controls., Methods: Thirty recently detoxified patients with alcohol addiction, and 31 healthy control subjects, were assessed in a Go and a NoGo condition, each using three visual stimuli: tea, juice and beer. In the "Go" condition, subjects had to respond to the juice (12.5 %) and the beer stimulus (12.5 %), and ignore the tea picture (75 %). In the "NoGo" condition, subjects had to respond to the tea picture (75 %) and ignore the juice and the beer picture (12.5 % each). The subjects' EEGs were analyzed with regard to the occipital P100 and N170 ERP components. Patients were then evaluated for relapse 3 months after this initial assessment., Results: P100 amplitudes differed between conditions and between stimuli, and we found a condition x electrode interaction. However, none of these P100 results involved group or relapse-status effects. N170 amplitudes in patients were elevated as compared to controls. Additionally, patients' heightened N170 amplitudes in response to the alcohol-related (beer) stimulus were found only under the NoGo condition, where subjects had to react to the frequent tea stimulus and ignore the beer and the juice stimuli, thus resulting in a condition x stimulus x group interaction. Patients reporting relapse in a 3-month follow-up assessment showed larger NoGo N170 alcohol cue-related ERP amplitudes and increased depression scores as compared to patients who stayed abstinent. Depression was related to shortened P100 latencies in patients, but unrelated to the N170 NoGo cue-reactivity effect., Conclusions: Our results indicate a sensitivity of occipital ERPs to addiction-related stimuli when these act as non-targets. Recently detoxified patients may be vulnerable to addiction-related cues when these occur outside the focus of directed attention, thereby circumventing intentional control processes. Furthermore, ERPs to addiction-related stimuli may be useful as a predictor of abstinence success in recently detoxified patients.

Context-Self-report measures often underestimate the severity of symptoms of alcohol abuse. It is generally supposed that patients who abuse alcohol tend to minimize their drinking behavior. However, the validity of self-reports also can be influenced by external factors such as the setting. Objective-To investigate how the setting influences self-reporting on symptoms of alcohol abuse in patients with alcoholic liver disease. Design, Setting and Participants-Cross-sectional study in patients before liver transplant (n = 40) and patients in rehabilitation therapy (n = 44). Main Outcome Measure-Scores on the Munich Alcoholism Test, which consists of a self-report-scale and an expert-rating scale. Results-The discrepancy in scores on the self-report scale and the expert-rating scale differed significantly between patients before liver transplant and patients in rehabilitation therapy. Furthermore, patients in the rehabilitation therapy group reported higher alcoholism scores on the self-report questionnaire than did patients before liver transplant, but the groups did not differ in the expert evaluation value. Conclusion-The transplant setting seems to evoke minimizing in self-reports in patients with alcohol abuse. Minimizing or denying symptoms of alcohol abuse does not seem to be a specific characteristic of persons with alcohol abuse, as it is also caused by the circumstances. In the transplant setting, more attention should be given to the psychologically difficult situation for patients with potential alcohol abuse. Implementation of psychoeducational interventions in the treatment process before transplant could be a first step toward reaching this goal.

Genetic factors have as large role as environmental factors in the etiology of alcohol dependence (AD). Although genome-wide association studies (GWAS) enable systematic searches for loci not hitherto implicated in the etiology of AD, many true findings may be missed owing to correction for multiple testing. The aim of the present study was to circumvent this limitation by searching for biological system-level differences, and then following up these findings in humans and animals. Gene-set-based analysis of GWAS data from 1333 cases and 2168 controls identified 19 significantly associated gene-sets, of which 5 could be replicated in an independent sample. Clustered in these gene-sets were novel and previously identified susceptibility genes. The most frequently present gene, ie in 6 out of 19 gene-sets, was X-ray repair complementing defective repair in Chinese hamster cells 5 (XRCC5). Previous human and animal studies have implicated XRCC5 in alcohol sensitivity. This phenotype is inversely correlated with the development of AD, presumably as more alcohol is required to achieve the desired effects. In the present study, the functional role of XRCC5 in AD was further validated in animals and humans. Drosophila mutants with reduced function of Ku80-the homolog of mammalian XRCC5-due to RNAi silencing showed reduced sensitivity to ethanol. In humans with free access to intravenous ethanol self-administration in the laboratory, the maximum achieved blood alcohol concentration was influenced in an allele-dose-dependent manner by genetic variation in XRCC5. In conclusion, our convergent approach identified new candidates and generated independent evidence for the involvement of XRCC5 in alcohol dependence.

Objectives: The aim of this study was to assess the effectiveness, tolerability, and safety of alcohol relapse prevention with disulfiram in alcohol-dependent patients in opioid maintenance treatment under routine treatment conditions., Methods: Twenty-nine opioid maintenance treatment patients were observed from the beginning of outpatient disulfiram treatment for up to 6 months. Patients received disulfiram (mostly 300 mg/d) together with their daily opioid dose. Patients were assessed through urine screens for alcohol (ethyl gluconoride) and other drugs at least twice monthly; blood chemistry analyses after 1, 3, and 6 months; and clinical interviews after 3 and 6 months., Results: Most patients presented with somatic and/or psychiatric comorbidity and/or polydrug use at baseline. Half of the patients completed 6 months of disulfiram treatment. Alcohol use was low during disulfiram treatment. Levels of other drug use did not change. For most patients, 1 or more adverse events were reported, often mild and/or short lived. Three patients experienced severe adverse events attributable to disulfiram., Conclusions: Disulfiram is a viable treatment option for the high-risk population studied here. A close monitoring of side effects and adverse events is necessary, in particular, in patients with polysubstance use.

The α-Ca(2+)/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a 'molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKII(T286A) mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKII(T286A) mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKII(T286A) mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA-5-HT balance as a putative mechanism.

The upregulation of glutamatergic excitatory neurotransmission is thought to be partly responsible for the acute withdrawal symptoms and craving experienced by alcohol-dependent patients. Most physiological evidence supporting this hypothesis is based on data from animal studies. In addition, clinical data show that GABAergic and anti-glutamatergic drugs ameliorate withdrawal symptoms, offering indirect evidence indicative of glutamatergic hyperexcitability in alcohol-dependent subjects. We used proton magnetic resonance spectroscopy to quantify the glutamate (Glu) levels in healthy control subjects and in alcohol-dependent patients immediately after detoxification. The volumes of interest were located in the nucleus accumbens (NAcc) and the anterior cingulate cortex (ACC), which are two brain areas that have important functions in reward circuitry. In addition to Glu, we quantified the levels of combined Glu and glutamine (Gln), N-acetylaspartate, choline-containing compounds, and creatine. The Glu levels in the NAcc were significantly higher in patients than in controls. Craving, which was measured using the Obsessive Compulsive Drinking Scale, correlated positively with levels of combined Glu and Gln in the NAcc and in the ACC. The levels of all other metabolites were not significantly different between patients and controls. The increased Glu levels in the NAcc in alcohol-dependent patients shortly after detoxification confirm the animal data and suggest that striatal glutamatergic dysfunction is related to ethanol withdrawal. The positive correlation between craving and glutamatergic metabolism in both key reward circuitry areas support the hypothesis that the glutamatergic system has an important role in the later course of alcohol dependence with respect to abstinence and relapse.

The impact of alcoholism (ALC) or alcohol dependence on the neural mechanisms underlying cognitive and affective empathy (i.e. the different routes to understanding other people's minds) in schizophrenic patients and non-schizophrenic subjects is still poorly understood. We therefore aimed at determining the extent to which the ability to infer other people's mental states and underlying neural mechanisms were affected by ALC. We examined 48 men, who suffered either from ALC, schizophrenia, both disorders or none of these disorders, using functional magnetic resonance imaging while performing on a mind reading task that involves both cognitive and affective aspects of empathy. Using voxel-based morphometry, we additionally examined whether between-group differences in functional activity were associated with deficits in brain structural integrity. During mental state attribution, all clinical groups as compared with healthy controls exhibited poor performance as well as reduced right-hemispheric insular function with the highest error rate and insular dysfunction seen in the schizophrenic patients without ALC. Accordingly, both behavioral performance and insular functioning revealed schizophrenia × ALC interaction effects. In addition, schizophrenic patients relative to non-schizophrenic subjects (regardless of ALC) exhibited deficits in structural integrity and task-related recruitment of the left ventrolateral prefrontal cortex (vlPFC). Our data suggest that ALC-related impairment in the ability to infer other people's mental states is limited to insular dysfunction and thus deficits in affective empathy. By contrast, mentalizing in schizophrenia (regardless of ALC) may be associated with insular dysfunction as well as a combination of structural and functional deficits in the left vlPFC., (© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.)

Objectives: This comparative study investigated consumption patterns, comorbidity and treatment utilization of opioid addicts in six European cities (Athens, Essen, London, Padua, Stockholm, Zurich)., Subjects and Methods: Data were collected by structured face-to-face interviews. The representative sample comprises 599 addicts (100 patients per centre, 99 in London) at the start of a treatment episode., Results: Patients were dependent on opioids for about 10 years. Regional differences were significant regarding the patients' drug consumption pattern and their method of heroin administration (up to a fourth of the patients in Essen, London and Zurich usually smoke heroin). Concomitant use of benzodiazepines, cannabis and alcohol was common in all regions with the German and English samples showing the highest level of polydrug use. The prevalence of major depression was high in all regions (50%). Stockholm and London patients worry most about their physical health. Differences in the amount of needle sharing and especially in the use of public health service were prominent between the sites. Opioid addiction was a long-term disorder associated with a high burden of comorbidity and social problems in all cities., Conclusion: The results of the study show significant interregional differences of opioid addicts which might require different treatment strategies in European countries to handle the problem., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1333 male in-patients with severe AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 2168 controls. These included 487 patients and 1358 controls from a previous GWAS study by our group. All individuals were of German descent. Single-marker tests and a polygenic score-based analysis to assess the combined contribution of multiple markers with small effects were performed. The single nucleotide polymorphism (SNP) rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance [P = 1.27E-8, odds ratio (OR) = 1.46]. Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (P = 1.24E-7, OR = 1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score-based approach produced a significant result (P = 9.66E-9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result may indicate that many more AD susceptibility genes still await identification., (© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.)

Aims: The aim of this randomized, controlled, multisite trial was to evaluate the efficacy of combined treatment with integrative behaviour therapy (IBT) and acamprosate on drinking behaviour in detoxified alcohol-dependent patients., Methods: A total of 371 patients were randomized to one of the three treatment conditions: IBT plus acamprosate, IBT plus placebo, or supportive counselling ('treatment as usual', TAU) plus acamprosate. The main outcome was success rate, i.e., rate of abstinence plus improvement according to the criteria of Feuerlein and Küfner (1989), at the end of the six-month treatment phase and at the subsequent six-month follow-up. Drinking status was validated by blood parameters (CDT, GGT, and MCV). Data were analyzed by an intent-to-treat model and missing data were classified as relapse., Results: The success rates at the end of treatment under both TAU plus acamprosate (37.7%) and IBT plus placebo (48%) almost reached the levels derived from the literature. However, adding acamprosate to IBT did not result in the expected increase in success rate (IBT plus acamprosate: 47.6%), and success rates did not differ significantly between groups. Similarly, there was no significant difference between treatment success rates at follow-up., Conclusion: The results suggest that the combination of acamprosate and IBT is not more effective than treatment with either IBT or acamprosate alone. However, the two acamprosate conditions differed in success rate by about 10%, which might constitute a clinically relevant though statistically non-significant effect., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: To compare two inpatient symptom-triggered pharmacological treatments of acute alcohol withdrawal (AWS) (clomethiazole vs. clonazepam)., Methods: Prospective observational comparison within a quality improvement project. Because of a need for extra precautions against complications such as seizures and severe respiratory complaints, patients with a history of withdrawal seizures or complications with clomethiazole in their history were automatically assigned to the clonazepam group. The remaining patients were alternately assigned either to the clonazepam group (n = 38 altogether) or the clomethiazole group (n = 36). Rescue medication could consist of adding either extra clonazepam or clomethiazole. Effectiveness was measured by Clinical Global Impression Scale, Revised Clinical Institute Withdrawal Assessment for Alcohol Scale, Mainz Alcohol Withdrawal Scale, Essen Self-Assessment-Alcohol Withdrawal and attrition rate. Safety and tolerability was estimated from adverse clinical events. Secondary outcome values were heart rate, blood and pulse pressure., Results: There were no significant differences between the treatments with respect to primary and secondary effectiveness measures, safety or tolerability or duration of medication treatment. Both reduced the severity of initial withdrawal symptoms below 20% up to the ending of withdrawal medications. No withdrawal seizure or delirium occurred., Conclusion: Both score-driven treatments were equally effective, safe and well tolerated in this setting. This is the first study demonstrating the utility of clonazepam in the treatment of AWS syndrome.

Aims: Anticonvulsants are increasingly being advocated for the treatment of acute alcohol withdrawal syndrome (AWS) to avoid the addictive properties of established medications. Because earlier works showed that moderate gabapentin doses were too low to clearly ameliorate severe AWS, we tested a higher gabapentin entry dose., Methods: Inpatients (n = 37) with severe alcohol withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-AR) score > or =15 points) were given gabapentin 800 mg, and if their symptom score reduced within 2 h, they were termed 'early responders' and were then treated for 2 days with 600 mg gabapentin q.i.d. (i.e. a total of 3200 mg in the first 24 h) before beginning a taper., Results: Twenty-seven (73%) were early responders (baseline CIWA-AR improved from 17.3 +/- 2.6 to 8.0 +/- 3.6 points). In the remaining 10 patients, baseline CIWA-AR deteriorated within 2 h (from 20.1 +/- 4.6 to 21.5 +/- 4.65 points). These patients were switched to clomethiazole (n = 4) or clonazepam (n = 6), which is the usual treatment. Three of the 'early responders' worsened in the next 36 h and were then reclassified and treated as 'non-responders'. Among them, two developed an epileptic seizure., Conclusion: Oral 800 mg gabapentin (loaded up to 3200 mg in the first 24 h) is helpful only in reducing less severe and less complicated acute AWS.

Context: Alcohol dependence is a serious and common public health problem. It is well established that genetic factors play a major role in the development of this disorder. Identification of genes that contribute to alcohol dependence will improve our understanding of the mechanisms that underlie this disorder., Objective: To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and a follow-up study in a population of German male inpatients with an early age at onset., Design: The GWAS tested 524,396 single-nucleotide polymorphisms (SNPs). All SNPs with P < 10(-4) were subjected to the follow-up study. In addition, nominally significant SNPs from genes that had also shown expression changes in rat brains after long-term alcohol consumption were selected for the follow-up step., Setting: Five university hospitals in southern and central Germany., Participants: The GWAS included 487 male inpatients with alcohol dependence as defined by the DSM-IV and an age at onset younger than 28 years and 1358 population-based control individuals. The follow-up study included 1024 male inpatients and 996 age-matched male controls. All the participants were of German descent., Main Outcome Measures: Significant association findings in the GWAS and follow-up study with the same alleles., Results: The GWAS produced 121 SNPs with nominal P < 10(-4). These, together with 19 additional SNPs from homologues of rat genes showing differential expression, were genotyped in the follow-up sample. Fifteen SNPs showed significant association with the same allele as in the GWAS. In the combined analysis, 2 closely linked intergenic SNPs met genome-wide significance (rs7590720, P = 9.72 x 10(-9); rs1344694, P = 1.69 x 10(-8)). They are located on chromosome region 2q35, which has been implicated in linkage studies for alcohol phenotypes. Nine SNPs were located in genes, including the CDH13 and ADH1C genes, that have been reported to be associated with alcohol dependence., Conclusions: This is the first GWAS and follow-up study to identify a genome-wide significant association in alcohol dependence. Further independent studies are required to confirm these findings.

Because of promising data from animal studies the clinical trials on anticonvulsants for the treatment of alcohol disorder have been accumulating in the last 40 years. A comprehensive research of various data bases (MEDLINE, EMBASE, Cochrane) was performed. Here, we present the trials found together with an estimation of their evidence according to the guidelines of the "Arzneimittelkommission der deutschen Arzteschaft". We examined the clinical studies conducted for the treatment of alcohol withdrawal syndrome, for relapse prevention/consumption reduction as well as for the treatment of co-morbide psychiatric disorders. The study analysis has not resulted in any safe alternative to benzodiazepines, clomethiazole or carbamazepine in the treatment of the stronger alcohol withdrawal syndrome. The material is also insufficient with regard to relapse prevention/consumption reduction or to the treatment of co-morbide psychiatric disorders. The safest proof of effect is currently topiramate (consumption reduction) and valproate (alcohol dependence with bipolar disorder). However, first positive results must be confirmed in well controlled studies with a much longer duration. Baclofen und several anticonvulsants such as valproate, oxcarbazepine and gabapentin demonstrate a potential to aid in the treatment of alcohol disorder. Currently, there exists any published controlled study for levetiracetam, which would be well suited in the treatment of alcoholism due to its favorable safety profile and low pharmacological interaction potential.

Background: There has been an increase of cannabis-related disorders in Germany during the last 10 years. According treatments are being established, however little is known about the treatment populations., Methods: The population of an outpatient treatment program for diagnosis and therapy of cannabis-related disorders was investigated using a structured interview (based on EuropASI, SCID-I) regarding sociodemographic variables, history of addiction, consumption patterns, and psychiatric comorbidity., Results: The 90 patients studied had a mean age of 27.5+/-6.6 years; 82% were male. They claimed averages of cannabis consumption for 11+/-7 years and current amount at 1.9 g per day. Alcohol problems were also common in this sample. High percentages were shown regarding unemployment, living alone, and problems with the law. Comorbid psychiatric disorders were diagnosed in 42% of patients., Conclusions: The patients were chronic users of cannabis with extensive psychosocial problems. Therapy of cannabis-related disorders should therefore include treatment for comorbidities and social care besides the treatment for addictive behavior.

Due to demographic trends and an aging cohort, which has higher rates of substance abuse than any previous generation, an increase in numbers of elderly alcohol abusers is predicted. The number of older alcohol dependent adults in Germany has been estimated to 400 000, the prevalence of risky use up to 2 million. Despite this reported high prevalence, patients over age 60 are seldom seen attending in- or outpatient treatment programs for alcohol dependence. In addition, little is known about this growing population of older adults with alcohol-related disease, e. g. regarding course of alcohol addiction, consumption patterns, somatic and mental comorbid disorders. This article shows the state of research in this area and reviews clinically-relevant concepts related to identifying, assessing and treating older adults with alcohol-related disability. Emphasis will be placed on the psychotherapy-methods of brief interventions and cognitive-behavioral therapy and on the pharmacological approaches for treating alcohol dependence with disulfiram, acamprosate and naltrexone.

There is a high association between alcohol and nicotine dependence. Compared to one particular dependence, associated nicotine and alcohol dependence are more severe and the course is more unfavourable for each dependence. This also applies to the sequels of dependence regarding physical health and cognitive functions. Possible biological causes for this high comorbidity are 1) an additive rewarding effect by combined consumption, 2) substance interaction with an impact on receptor activation and metabolism which results in reduction of adverse acute alcohol effects, and 3) a combined genetic disposition for both addictions. From a psychological point of view the association of both acts of use is learned. There is no evidence for the commonly presumed fundamental lack of interest, motivation, and ability for smoking cessation in alcohol dependent patients. The outcome of smoking cessation programs, however, is less successful compared to smokers without alcohol problems. Respective studies have used the common therapeutic strategies for nicotine addiction. Specifically adapted strategies for patients with a dual dependence are required.

In this investigation, the hypothesis was tested whether the selective dopamine D2/D3 receptor antagonist tiapride is effective in maintaining abstinence after detoxification in alcohol-dependent patients. The rationale of the study was based on the relevance of the dopaminergic system for addictive behaviour as well as some preliminary studies. A multi-centre, randomized, double-blind, placebo-controlled, parallel-group study was conducted. A total of 299 detoxified alcohol-dependent patients (ICD-10: F10.2) received either tiapride (300 mg/d) or placebo over a 24-wk study period. Subjects with severe comorbid psychiatric disorder such as schizophrenia or Wernicke-Korsakoff syndrome were excluded. Primary outcome variable was the time to first relapse with relapse defined as any alcohol consumption after detoxification. Data analysis was done with Kaplan-Meier estimates with log-rank test (one-sided, p<0.05). Tiapride was not superior to placebo in maintaining abstinence. The time to first relapse was 71 d in the tiapride group and 92 d in the placebo group (log-rank test, p=0.9895). Relapse rate was higher in the intervention group (54.4%) than in the control group (40.7%). Like the dopamine antagonist flupenthixol, tiapride was not effective in maintaining alcohol abstinence. Regarding the high success rate in the placebo group the influence of psychosocial treatment in studies investigating drug effects on the course of alcohol dependence has to be considered.

Addictive diseases such as alcoholism, nicotine or opiate addiction show sex-specific characteristics. These apply to epidemiological data, the psychosocial conditions for the development of the addiction,the symptoms, possible consequences for pregnancy and breastfeeding, the course of the addiction, as well as its treatment. As a whole, men are more frequently substance-dependent than women. This is true for all types of addiction and for each individual substance - with the exception of benzodiazepines and analgesics to which women are equally or more frequently dependent. Moreover, women have a different consumption pattern from men. Epidemiological surveys on illegal drugs frequently do not present sex-specific data. There also is still a great need for research in regards to sex-specific therapeutic strategies.

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