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Abstract Aim: This detailed cross-sectional analysis, obtained from a sample of alcohol-dependent patients, attempts to compare multiple methods that have been created to classify or subtype alcoholics. Methods: The sample comprised 318 alcohol-dependent patients recruited from the alcoholism unit (NETER) of the Psychiatric Service of Santa Maria University Hospital in Lisbon (Portugal). All subjects were evaluated during the outpatient therapeutical programme for operationalized criteria, reported by each alcoholism typology. Results: Regarding concordance agreement (kappa values) for the three type 1/Il classifications, von Knorring versus Sullivan yielded the higher rate of agreement, followed by von Knomng versus Gilligan and Gilligan versus Sullivan criteria. Chi-square comparisons showed a significant overlap between Babor type A and Cloninger type I of von Knorring and Sullivan. Over-two-type classifications showed the following significant positive relations: Lesch type I versus NETER heredopathic subtype; Lesch type II versus NETER anxiopathic subtype and Babor type A; Lesch type III versus NETER tymopathic subtype; Lesch type IV versus Cloninger type H of von Knorring and Sullivan criteria; and NETER adictopathic subtype versus Cloninger type II of von Knomng, Sullivan and Gilligan criteria. Conclusions: There is a significant overlap across many of the multivariate alcoholic subtypes purposed, in which much of the concordance is a function of common characteristics in subtype operationalization. Commonalities among these different subtyping classification systems offers the possibility of identifying important dimensions that better differentiate individuals among problem drinker's populations. [ABSTRACT FROM AUTHOR]

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on October 1, 2004. The organizers and cochairs were Nassima Ait-Daoud, MD, and Gerhard A. Wiesbeck, MD. The presentations included the following:L (1) The Role of Nicotinic Acetylcholine Receptors in Alcohol-Seeking Behavior, by Przemyslaw Bienkowski, MD, PhD; (2) Utilization of Linkage Analysis Combined with Microarray Technology to Identify Genes and Mechanisms Underlying Nicotine and Alcohol Use and Abuse in Humans and Rodents, by Ming D. Li, PhD; (3) Smoking and Alcoholic Chronic Pancreatitis: The Underestimated Risk?, by Roland H. Pfützer, MD; (4) Anticraving Medication in Alcohol and Nicotine Dependence, by Otto M. Lesch, MD, PhD; and (5) Pharmacotherapy for Promotion of Abstinence from Nicotine Among Alcohol-Dependent Individuals, by Bankole A. Johnson, DSc, MD, PhD. [ABSTRACT FROM AUTHOR]

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on September 30, 2004. The organizers and cochairs were Bankole A. Johnson, DSc, MD, PhD, and Karl Mann, MD. The presentations included the following: (1) A Perspective from Academia, by Bankole A. Johnson, DSc, MD, PhD; (2) A Perspective from NIAAA, by Mark L. Willenbring, MD; (3) A Perspective from US Clinical Practice, by Robert M. Swift, MD, PhD; (4) A European Perspective on Medications Development, by Otto M. Lesch, MD, PhD, and (5) A Scandinavian Perspective on Evidence-Based Addiction Treatment, by Mats Berglund, MD. [ABSTRACT FROM AUTHOR]

Background: About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence.Methods: In this multicentre, double-blind, placebo-controlled study, we recruited 455 patients, aged 18-65 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1998 mg daily for bodyweight > 60 kg; 1332 mg daily for < or = kg) or placebo for 360 days. Patients were assessed on the day treatment started and on days 30, 90, 180, 270, and 360 by interview, self-report, questionnaire, and laboratory screening. Patients were classified as abstinent, relapsing, or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure.Findings: Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication. The acamprosate (n = 224) and placebo (n = 224) groups were well matched in terms of baseline demographic and alcohol-related variables. 94 acamprosate-treated and 85 placebo-treated patients completed the treatment phase: of those withdrawn, 104 (52 in each group) relapsed, 69 (33 vs 36, respectively) were lost to follow-up, 63 (31 vs 32) refused to continue treatment, 16 (15 vs 11) had concurrent illness, three (two vs one) died, ten (six vs four) had adverse side-effects, one (acamprosate treated) received the wrong medication, and three (placebo treated) were non-compliant. The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period (p < 0.001, Mantel-Cox). At the end of treatment, 41 (18.3%) acamprosate-treated and 16 (7.1%) placebo-treated patients had been continuously abstinent (p = 0.007). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (138.8 [SD 137.5] vs 103.8 [119.0] days; p = 0.012). 148 patients (79 acamprosate, 69 placebo) completed 27 months follow-up: 27 (11.9%) acamprosate-treated and 11 (4.9%) placebo-treated patients remained continuously abstinent, and the mean cumulative abstinence duration was 230.8 days (259.1) and 183.0 days (235.2), respectively. Apart from occasional diarrhoea, there was no difference in side-effects between groups.Interpretation: Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects., Methods: This was a phase III, 6-month, 25-site, randomized, placebo-controlled clinical trial using AD04 to treat DSM-V-categorized AUD individuals who were pre-stratified into the endophenotypes of heavy or very heavy drinking individuals and possessed a pre-defined profile of genetic variants related to the serotonin transporter and serotonin-3AB receptor. Participants (N = 303) presented moderate to severe AUD, >80 % were men, mostly in their fifties, and >95 % were of European descent. Low-dose AD04 (approx. 033 mg twice daily) or a matching placebo was administered twice daily for 6 months. Brief Behavioral Compliance Enhancement Treatment (BBCET [53]) was administered every two weeks to enhance medication compliance and clinic attendance., Results: There was a significant reduction in the monthly percentage of heavy drinking days, PHDD (-46·7 % (2·7 %), 95 %CI: -52·1 % to -41·2 % vs. -38·1 % (2·9 %), 95 %CI: -43·8 % to -32·5 %, respectively; LS mean difference=-8·5 %; p = 0.03) among AD04-treated vs. placebo-receiving heavy drinking individuals at month 6. Heavy drinking individuals were also less likely to be diagnosed with AUD [Month 1: -32·0 % (2·8 %), 95 %CI: -37·5 % to -26·5 % vs. -23·2 % (2·9 %), 95 %CI: -28·9 to -17·5 %; LS mean difference= -8·8 %; p = 0·026)], and improved on the WHO quality of life BREF scale with a significant effect for at least a 1-level downward shift (OR = 3.4; 95 % CI: 1·03-11·45, p = 0·044). Importantly, heavy drinking individuals, as distinct from very heavy drinking individuals, were the bio-psychosocial endophenotype more predictive of therapeutic response to AD04. AD04 had an exceptional safety and tolerability profile, like the placebo's., Conclusions: In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure., Competing Interests: Declaration of competing interest All authors are paid consultants of Adial Pharmaceuticals Inc. Vinzant Schuyler and Bankole Johnson are officers of Adial Pharmaceuticals Inc., (Copyright © 2024. Published by Elsevier B.V.)

Background: The increasing prevalence of alcohol use disorder (AUD) and the parallel surge in alcohol-associated liver disease (ALD) emphasize the urgent need for comprehensive alcohol management strategies. Low-dose ondansetron (AD04, a 5-HT3 antagonist) was shown recently to be a promising treatment for AUD with a specific genotypic profile (5-marker). The liver safety of AD04 has never been evaluated in subjects with AUD. The aim of the present study was to assess the liver safety profile of AD04 compared with placebo in subjects with AUD., Methods: Liver biochemical parameters were assessed in subjects with AUD with a 5-marker genetic profile who participated in a Phase 3 randomized controlled trial and received either twice-daily, low-dose AD04 (ondansetron 0.33 mg twice daily) or matching placebo, combined with brief psychosocial counseling. ALT, AST, GGT, Serum Bilirubin, MCV, and Prothrombin were evaluated at weeks 0, 12, and 24. Adverse cardiac events, general well-being, and study completion were also assessed., Results: Low-dose AD04 did not significantly change biochemical markers of liver injury, such as ALT, AST, and Serum Bilirubin. While patients with AUD displayed elevated GGT levels, typically associated with increased alcohol consumption, this parameter remained unaffected by low-dose AD04. Notably, no significant adverse effects were observed due to oral low-dose AD04 treatment., Conclusions: Low-dose AD04 has the potential to be a safe treatment option for subjects with AUD and ALD, indicating the need for an RCT for this specific cohort. Such a trial would pave the way for the design of a precision treatment for combined AUD with ALD., Competing Interests: Declaration of competing interest All authors are paid consultants of Adial Pharmaceuticals Inc. Bankole Johnson is an officer of Adial Pharmaceuticals Inc., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Autonomic symptoms in alcohol withdrawal syndrome (AWS) are associated with a sympathetic-driven imbalance of the autonomic nervous system. To restore autonomic balance in AWS, novel neuromodulatory approaches could be beneficial. We conducted a pilot trial with percutaneous auricular vagus nerve stimulation (pVNS) in AWS and hypothesized that pVNS will enhance the parasympathetic tone represented by a reduction of pupillary dilation in a parasympatholytic pharmacological challenge., Methods: Thirty patients suffering from alcohol use disorder, undergoing AWS, and stable on medication, were recruited in this open-label, single-arm pilot trial with repeated-measure design. Peripheral VNS (monophasic volt impulses of 1 msec, alternating polarity, frequency 1 Hz, amplitude 4 mV) was administered at the left cymba conchae for 72 h, followed by pupillometry under a tropicamide challenge. We assessed craving with a visual analog scale. We used pupillary mean as the dependent variable in a repeated-measures ANOVA (rmANOVA)., Results: A repeated-measures ANOVA resulted in a significant difference for pupillary diameter across time and condition (F (2,116)  = 27.97, p < .001, η p 2  > .14). Tukey-adjusted post hoc analysis revealed a significant reduction of pupillary diameter after pVNS. Alcohol craving was significantly reduced after pVNS (p < .05, Cohen's d = 1.27)., Conclusion: Our study suggests that pVNS activates the parasympathetic nervous system in patients with acute AWS, and that this activation is measurable by pupillometry. To this end, pVNS could be beneficial as a supportive therapy for AWS. Potential confounding effects of anti-craving treatment should be kept in mind., Competing Interests: Declaration of competing interest SK holds, shares, and is employed by AURIMOD GmbH. JCS holds shares of the Multisana GmbH. All other authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients., Methods: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively., Results: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001., Conclusions: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press.)

Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation., Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients., Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3-3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period., Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6-68.5; p  = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites ( n  = 3-66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p  = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated., Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD., Trial Registration: ClinicalTrials.gov Identifier: NCT04648423.

Background: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD., Methods: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis., Results: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months)., Conclusions: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD., (© 2021 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.)

Introduction : Sodium oxybate (SMO) has been approved in Italy and in Austria for the treatment of alcohol use disorder (AUD). This study describes the cumulative postmarketing and clinical safety experience with SMO in AUD. Areas covered : Safety data for SMO at approved posology in AUD were identified from: (i) the clinical trial registries of the US National Institutes of Health (NIH) and the European Medicines Agency (EMA), (ii) reports from the biomedical literature and (iii) available pharmacovigilance safety information from the EMA. Expert opinion : Safety data from 3 recent large randomized clinical studies (520 participants) and 43 earlier clinical studies (2547 participants) showed that SMO has a good safety profile in AUD patients. The safety profile was confirmed by pharmacovigilance data resulting from 299 013 patients exposed to SMO in Austria and Italy. Main adverse events were transitory dizziness and vertigo. Serious adverse events were rare. No death attributable to SMO has been reported. Risks of abuse or dependence are low in patients without psychiatric comorbidities or poly-drug use. The adverse events of SMO are transitory and do not require discontinuation of treatment. SMO abuse or dependence are extremely rare in patients without psychiatric comorbidities or poly-drug use.

Aims: Alcohol is an important risk factor for morbidity and mortality, especially within the European region. Differences in per capita consumption and drinking patterns are possible reasons for regional differences and diverging trends in alcohol-related health outcomes., Methods: Twenty-nine countries within the World Health Organization (WHO) European region were evaluated for trends and predictions in alcohol-related deaths within the last four decades using data available from the WHO Health for All database., Results: Between 1979 and 2015, age-standardised death rates due to selected alcohol-related causes decreased significantly for both sexes in all assessed countries of the WHO European region, but regional differences are still pronounced. Assuming a similar trend in the future, the model predicted a further decrease until the year 2030., Conclusion: Even though alcohol-related mortality may have decreased within the last decades, the detrimental effects of alcohol consumption and alcohol dependence remain a considerable burden of disease within Europe., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABA B receptors and extrasynaptic GABA A receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL., (© 2018 Society for the Study of Addiction.)

This study intended to determine whether former and current ADHD symptomatology is associated with suicidal ideation in a non-clinical sample of 18 year old males. We performed a cross sectional descriptive study of 3280 men during the examination for military service. The investigation included a screening for substance abuse, past (WURS) and current (ADHD symptom checklist) ADHD symptomatology and an interview about suicidal ideations. We found a correlation of suicidal ideations with a history of ADHD symptomatology. ADHD symptoms were strongly consistent over time. These results indicate that a history of (diagnosed or undiagnosed) ADHD could be a predictor for suicidal ideations. Surveying a history of ADHD in primary care might help identify subjects at risk for suicidal tendencies., Competing Interests: Compliance with ethical guidelinesConflict of interestJ. Huemer, A. Riegler, S. Völkl-Kernstock, A. Wascher, O. M. Lesch, H. Walter, and K. Skala declare that they have no competing interests.Ethical standardsEthical approval was obtained from the Ethics Committee of the Medical University of Vienna as well as the Ethics Committee of the Austrian Armed Forces. Informed consent was obtained from each participant.

Background: This study intended to determine whether certain traits of temperament are associated with former and current ADHD symptomatology in a non-clinical sample of 18 year old males., Methods: We performed a cross sectional descriptive study of 3280 men during the examination for military service. The investigation included a socio-demographic questionnaire, screening for substance abuse, temperament (TEMPS-M), past (WURS) and current (ADHD symptom checklist) ADHD symptomatology., Results: We found a correlation of cyclothymic (p<.001), irritable (p<.001) and anxious (p<.05) temperament with occurrence and severity of past and present ADHD symptomatology. No significant correlation has been detected for hyperthymic and depressive temperament. Judged retrospectively, ADHD symptoms were strongly consistent over time., Limitations: The sample consists of men only. These had to be fit enough to be enlisted for military service; men with severe mental or physical disorders were thus excluded. Furthermore, the cross-sectional study design does not allow making conclusions about the temporal relationships between ADHD symptoms and substance misuse., Conclusions: These results indicate that a temperament based approach towards those affected by ADHD might be useful. Subtyping ADHD by integrating temperament profiles in diagnosis and treatment of the disorder could help explain some of the heterogeneity of the disease., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The current nosological classifications may describe a syndrome of "alcoholism" that is too heterogeneous to produce prognostic models for clinical management. Multidimensional alcoholism typologies (ATs) could represent a valuable paradigm in the search for targeted treatment. The main goal of this study was to evaluate the clinical implications of 3 empirically-validated ATs, focusing on various measures of clinical performance., Method: This was a 3-month naturalistic study in which drinking status, and participation in the clinical protocol and group psychotherapy were recorded and used as indicators of treatment performance. The clinical profiles of the subtypes were also compared and graphically presented. Alcohol-dependent outpatients were classified according to the Cloninger, Lesch, and NETER typologies., Results: The results showed that the type II (Cloninger), type IV (Lesch), and sociopathic and addictopathic (NETER) subgroups showed a worse outcome in terms of abstinence rates and clinical healthcare resource use., Conclusions: Our findings point to the need to differentiate multidimensional alcoholism subtypes before planning the clinical management of alcohol use disorders.

Aims: The first aim of this study is to investigate the impact of different temperaments in opiate dependency patients. The second aim of this study is to define therapy relevant subgroups in opiate addiction for further basic clinical research and therapy., Methods: In the time period from September to November 2010, 101 patients (72 males and 29 females) which fulfilled the diagnosis of opiate dependency according to DSM-IV-TR were recruited consecutively. All patients were in treatment at the Oum El Nour rehabilitation center/Lebanon (Inpatient and Outpatient groups). Lesch Alcoholism Typology modified for assessment of opiate addicts, and the briefTEMPS-M, Arabic version were used., Results: The organic Type IV group was the most prevalent (48.5%) among the sample followed by the Affective Type III group (41.6%) and the minority represented the two other types (I & II). The organic Type IV group represented the major type in the cyclothymic and anxious temperament. In the contrary the other two groups (I & II) were the minority among the cyclothymics., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Suicide is a major health problem accounting for up to 1.5 percent of all deaths worldwide and represents one of the most common causes of death in adolescents and young adults. A number of studies has been performed to establish risk factors for suicide in patients with psychiatric disorders including temperamental features. This study set out to assess the relationship between suicidal ideation and temperament in young adults., Methods: A cross-sectional sample of healthy college students (n=1381) was examined using a self-rating questionnaire. Suicidal ideation, social background, educational status, substance abuse, and affective temperament according to TEMPS-M were assessed. Predictors of lifetime suicidal ideation were examined in multivariate logistic regression analyses., Results: Suicidal ideation was reported by 12.5% of all subjects at some point in their life and was higher in nicotine dependents, youth with alcohol related problems and users of illicit substances as well as in youth with lower educational status. Lifetime suicidal ideation was associated with the anxious, depressive and cyclothymic temperament in both sexes and the irritable temperament in males. These results remained significant after adjustment for smoking status, frequency of alcohol consumption, drug experience and educational status in a multivariate logistic regression analysis., Limitations: The use of self-rating instruments always reduces objectivity and introduces the possibility of misreporting., Conclusions: Considering the fact that many subjects completing suicide have never been diagnosed with mental disorders it might be reasonable to include an investigation of temperament in screenings for risk of suicide. This might be especially useful for health care professionals without mental health care background., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Substance abuse is among the leading causes of preventable diseases and premature death but reasons and conditions leading to substance abuse are complex and multifaceted. Different models of abuse and dependence assume an underlying emotional vulnerability. Individual behavioral and emotional reactivity patterns of personality are considered in the concept of temperament but studies linking different types of temperament with substance use are rare., Methods: In this study we investigated 1380 inhabitants (59.7% females; 40.3% males) of residential student homes in Austria, using Akiskals TEMPS-M auto-questionnaire. Further, we administered the CAGE- and the HSI-questionnaire and assessed other psychoactive substance use to examine associations between traits of temperament and substance abuse using ordered logistic regression., Results: Temperaments follow different distributions in both genders: Women have higher scores on the depressive, cyclothymic, and anxious subscales and lower scores on the hyperthymic scale than men. The cyclothymic and particularly irritable temperament serve as predictors of self-reported nicotine dependence, alcohol abuse and cannabis use. Interestingly, the depressive temperament seems to be protective against self-reported cannabis use., Limitations: Substance abuse assessment is based on self-reports only and urine drug and blood tests were not performed. Also, the history of substance abuse is not documented thus temperamental factors could have been influenced by substance abuse if the time of onset was in early adolescence. The study design was cross-sectional, thus limiting causal interpretations., Conclusions: It might be important to consider temperamental traits as protective- and risk factors in the etiology, prevention and therapy of substance abuse in future., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Recent findings in basic scientific research, such as neurobiological and neuroimaging studies, have suggested common pathways for food and drug intake. It was hypothesized that both compete for the same brain reward sites, and that a higher body mass index (BMI) may be associated with lower substance use. The aim of this study was to investigate the relationship between BMI and substance use in a large sample of young male adults. The sample consisted of 1,902 18-year-old males from a province of Austria in a naturalistic cross-sectional setting. Questionnaires were administered to assess alcohol abuse and dependence (CAGE) and nicotine dependence (Heavy Smoking Index). Urine samples were collected to assess the prevalence of recent illicit drug use. Associations between BMI and substance use were calculated by means of logistic regression analyses. An inverse relationship between BMI and recent illicit drug use was found. This relationship remained significant after adjusting for possible confounding factors such as level of education, nicotine dependence, breath carbon monoxide (CO) levels, and alcohol abuse and dependence. No significant association was found between BMI and nicotine and alcohol dependence. A higher BMI was associated with lower illicit drug use in our sample of young adult males. These results provide further evidence for the hypothesis that food and drugs may compete for the same brain reward sites. , (Copyright © American Academy of Addiction Psychiatry.)

Background: During the last 20 years Austrian psychiatric services underwent fundamental changes, as a focus was set on downsizing psychiatric hospitals. Little is known about how restructuring of mental health services affected patients with major depression and suicide rates., Methods: Monthly hospital discharges from all hospitals in Austria with the diagnosis of unipolar major depression as primary reason for inpatient treatment were obtained for the time period between 1989 and 2008. These data were correlated with relevant parameters from the general health system, such as number of hospital beds, suicide rate, density of psychotherapists and sales of antidepressants., Results: While the number of psychiatric beds was reduced by almost 30%, the total annual numbers of inpatient treatment episodes for depression increased by 360%. This increase was stronger for men than for women. Further on this development was accompanied by a decrease in the suicide rate and an improvement in the availability of professional outpatient mental health service providers., Limitations: Only aggregated patient data and no single case histories were available for this study. The validity of the correct diagnosis of unipolar major depression must be doubted, as most likely not all patients were seen by a clinical expert., Conclusions: Our data show that although inpatient treatment for unipolar major depression dramatically increased, reduction of psychiatric beds did not lead to an increase of suicide rates., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Aims: N-terminal pro-BNP (NtBNP) has attracted attention as a biomarker for heart failure. The aims of our study are (a) to characterize the role of NtBNP as a biological marker in the setting of alcoholism; (b) to describe potential gender differences with respect to NtBNP; (c) to correlate NtBNP with other clinical and haemodynamic variables., Methods: We examined 83 alcohol-dependent patients according to International Classification of Disease 10th Revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV; 59 males and 24 females, age: 50 ± 10.5 years) referred to the department of psychiatry for alcohol withdrawal therapy. In these patients, we determined NtBNP, markers of alcohol abuse and transthoracic echocardiography to determine systolic left ventricular ejection fraction (EF). These measurements were repeated after alcohol withdrawal., Results: At Day 1 of alcohol withdrawal, 43 patients (52%; 27 males and 16 females) had elevated NtBNP levels (394.4 ± 438.7 pg/ml) despite normal EF (64.7 ± 6.2%). After withdrawal therapy (16.6 ± 7.8 days), NtBNP decreased significantly (228.6 ± 251.2 pg/ml; P < 0.01), despite unchanged EF (65.0 ± 5.8%; P = ns). This was the case in both males and females (328.9 ± 235.5 to 216.7 ± 194.3 pg/ml; P < 0.05 vs. 492.7 ± 635.7 to 246.6 ± 327.7 pg/ml; P < 0.05). Elevated NtBNP levels were related significantly to the history of arterial hypertension (P < 0.05)., Conclusion: This study highlights the fact that NtBNP can be elevated in the setting of alcoholism. The elevation in NtBNP is unrelated to EF and is reversible after alcohol withdrawal. We suggest a subclinical detrimental effect of alcohol abuse on cardiac function.

Aims: To assess the clinical and biological status of alcohol-dependent patients admitted to a psychiatric or a gastroenterological ward, assessing and comparing dimensions important for prescribing treatment for withdrawal and relapse prevention., Methods: Eighty patients, alcohol-dependent according to international classification of diseases tenth revision and diagnostic and statistical manual, text revised, version IV, admitted to the Vienna General Hospital between January 2005 and  November 2006, were examined, of whom 44 were admitted to the psychiatric ward and 36 to the gastroenterological ward. Dimensions of alcohol dependence were assessed using a computerized structured interview, the Lesch alcoholism typology (LAT). Biological markers and the model for end-stage liver disease (MELD) score defined the severity of alcohol-related physical disturbances., Results: As might be expected, gastroenterological patients had more advanced physical diseases than psychiatric patients, and affective disorders and suicidal tendencies were significantly commoner among the psychiatric patients. Thus, LAT Type II patients were overrepresented at the gastroenterological ward and LAT Type III patients at the psychiatric ward., Conclusion: The severity of somatic diseases and psychiatric disorders as well as the distribution of the four types according to Lesch differ between alcohol-dependent patients admitted to a psychiatric ward or a gastroenterological ward. Regarding the positive long-term outcome, different evidence-based medical treatment approaches for withdrawal and relapse prevention are needed for these patients.

The aim of the current study was the examination of exhaled breath carbon monoxide levels as a predictor for heaviness of smoking. In this regard, nicotine dependence was assessed among a representative sample of 1,870 Austrian male military conscripts in a cross-sectional setting. Participants completed the Heaviness of Smoking Index (a brief questionnaire for assessment of nicotine dependence), and their expired breath carbon monoxide levels were measured. The performance of carbon monoxide as a predictor of dependence levels was examined by means of Receiver-Operating-Characteristic Curve Analysis. Area Under the Curve, as well as sensitivity and specificity, were reported for each carbon monoxide cut-off level. The authors demonstrate that exhaled carbon monoxide levels serve as a satisfactory means to discriminate between smokers and non-smokers, yielding optimal discrimination at a cut-off level ≥ 5.5 parts per million (ppm), with a sensitivity of 95% and a specificity of 83%. However, the results indicate that carbon monoxide levels do not discriminate adequately between different levels of severity of nicotine dependence. The study demonstrates exhaled carbon monoxide as a useful marker of smoking status but not of nicotine dependence.

Diagnoses are made for identifying rather homogeneous groups of patients being thereby relevant for research and for therapy. Therefore diagnostic manuals, like the DSM-IV and the ICD-10 are subjected to changing knowledge derived from research on one hand and to changes of clinical necessities. The diagnosis of substance related disorders, published for DSM-IV in 1994 and for the ICD-10 in 1992, has proven of value for epidemiological research and economic validation. In spite of these advantages the concept has prove to be too broad and rather unspecific for research, specific therapeutic strategies and for defining an illness course. During the last 20 years research has yielded many criteria of interest, which never entered DSM IV or ICD-10, remaining therefore on the level of single items, which are nowadays additionally assigned to all patients (like e. g. early versus late onset) or on the level of typologies (like e. g. Lesch's typology) demanding different treatments. To give an example: acamprosate has lasting relapse preventing effects in Lesch types I and II, while naltrexone is effective in types III and IV. For rendering an expertise in Germany, the referring literature recommends to utilize Lesch's typology additionally to the ICD-10 diagnosis, especially when prognosis or therapeutic strategies are demanded. Since 1999 different expert groups strive for including new criteria into DSM IV and ICD-10. The revised manuals should include easily assignable items for severity of different arrays (time illness onset, co-morbidity, withdrawal symptoms, bridge symptoms and neurological sequela). Different therapy stages (e. g. withdrawal or relapse prevention) need a different weighting of individual symptoms (e. g. degree of intoxication, severity of withdrawal is needed for acute treatment, while an assignment of co-morbidity and personality factors is necessary for relapse prevention). This quantifier is rendered by Lesch's typology, which is available in the form of a computer programme, based on a decision tree (see also www.ausam.at - Typology according to Lesch). Non substance related disorders should enter other diagnostic categories, like e. g. impulse control disorders. A revised diagnostic classification suggests presently offered therapeutic strategies to follow up with necessary modifications. A tailor made therapy according to subgroups can result in better long term performance of therapies offered to persons suffering form substance related disorders., ((c) Georg Thieme Verlag KG Stuttgart-New York.)

Aim: The aim of the present study is to examine the distribution of plasma excitatory and inhibitory amino acids, according to the age and current breath alcohol levels (BrAl+/-), of alcohol-dependent patients., Participants and Methods: 78 alcohol-dependent patients (mean age=46.2+/-11 years, men/women=54/24) were clinically tested, including the determination of the major excitatory as well as inhibitory amino acids. The independent variables were gender, age and current alcohol consumption measured with the breath alcohol level (BrAl+/-status)., Results: In comparison to BrAl negatives, BrAl positives had higher plasma levels of glutamic acid (P=0.01) and proline (P=0.026), and lower levels of aminobutyric acid (P=0.002), serine (P=0.031) and urea (P=0.01). In the BrAl positives, no age effect was found related to the plasma amino acids. In contrast, the BrAl negatives displayed age-related differences. The older (>or=50 years) BrAl negative patients had higher plasma levels of cystine, tyrosine, citrulline and urea, and lower histidine levels, compared to the younger group (<50 years). In general, differences in plasma levels of certain amino acids were dependent on gender, BrAl status, age and biochemical markers (GGT, MCV) of alcohol abuse., Conclusions: Abstaining patients (BrAl-/) display age-related differences in AAs' distribution, while active drinking (BrAl+/) seems to even out those differences, underpinning the hypothesis that drinking mimics changes seen with advanced age.

Multiple lines of evidence suggest that the endocannabinoid system is implicated in the development of alcohol dependence. In addition, in animal models, the cannabinoid receptor 1 blocker rimonabant was found to decrease alcohol consumption, possibly by indirect modulation of dopaminergic neurotransmission. This was a 12-week double-blind, placebo-controlled, proof-of-concept study to assess the possible efficacy of the cannabinoid receptor 1 antagonist rimonabant 20 mg/d (2 x 10 mg) in the prevention of relapse to alcohol in recently detoxified alcohol-dependent patients. A total of 260 patients were included, 258 were exposed to medication, and 208 (80.6%) were men. Patients had an alcohol history of 15 years on average. More patients in the rimonabant group (94/131 [71.8%]) completed treatment compared with the placebo group (79/127 [62.2%]). Although there was a modest effect of rimonabant with respect to relapse rate, there were no statistically significant differences between treatment groups. Approximately 41.5% of the rimonabant group had relapsed to drinking at the end of the study compared with 47.7% of the placebo group (obtained from Kaplan-Meier-curve). Differences were more marked but not statistically significant in patients who relapsed to heavy drinking: 27.7% versus 35.6%, respectively. Safety and tolerance of the drug were good. Similar rates of adverse events were reported between the 2 groups; less patients experienced serious events or discontinued the treatment with rimonabant compared with placebo. Rates of depression-related events were low (3.8% with rimonabant compared with 1.6% with placebo). Patients on rimonabant lost weight (Mean, -1.7 kg) compared with baseline, whereas there was no such change in the placebo group. Weight loss was more pronounced in patients with a higher body mass index. In addition, there was a significant decrease in leptin levels in the rimonabant group compared with baseline. Lack of efficacy in this study may be explained by a very high response rate in the placebo group and a relatively short treatment duration. Taking the substantial numbers of animal studies suggesting a possible role of CB1 antagonists for the treatment of alcohol dependence into account, it seems worthwhile to further test cannabinoid blockers in the treatment of alcoholism.

Objective. To validate NAT (NETER's alcoholic typology), taking into account the differentiated distribution of the measures used as external criteria in alcohol-dependent sub-groups and its relationship with Lesch's alcoholic typology (LAT). Method. A sample of 133 alcohol-dependent patients integrated in the alcoholism unit of the Psychiatric Service of Santa Maria University Hospital were included in the study. Results and Conclusions. Convergent validity was assured by the agreement between the subtypes of the two typologies (NAT and Lesch), considering the same underlying model of alcoholism development: anxiopathic subtype of NAT and Type II (model of anxiety, alcohol as conflict solution) of Lesch and the tymopathic subtype of NAT and type III (model of depression, alcohol as antidepressant) of Lesch. Discriminant analysis (external criteria) showed significant differences between the subtypes in the following variables: gender; tobacco; beer and whisky consumption; daily average of drinks; clinical conditions such as delirium tremens, alcoholic blackouts and seizures; severity of alcohol-related problems; psychological dimensions such as psychological maturity and extroversion; and suicidal ideation during the alcohol consumption period. A more exhaustive description of alcoholic sub-groups may improve genetic studies of alcoholism and provide the alcoholic patient with an adequate specific therapeutic protocol.

The study investigated the non-inferiority of flupentixol compared to risperidone in the treatment of negative symptoms. In addition, the effects of flupentixol on mood and cognitive symptoms were explored. In a randomized, double-blind multicenter study, 144 non-acute schizophrenia patients with predominant negative symptoms were treated with a flexible dose of either flupentixol (4-12 mg/d) or risperidone (2-6 mg/d) for up to 25 weeks. In addition to a non-inferiority analysis, a principal component analysis (PCA) of the PANSS was performed post hoc. Regarding negative symptoms, flupentixol proved to be non-inferior to risperidone. Both drugs improved depressed mood with effect sizes favoring flupentixol. PCA suggested a five-factor structure. Effect sizes for the cognitive factor were up to 0.74 for flupentixol and up to 0.80 for risperidone. EPS scores were rather low and Parkinsonism improved in both groups, but anticholinergic drugs were prescribed significantly more frequently in the flupentixol group, which generally showed significantly more adverse events. Results indicate that the 1st generation antipsychotic flupentixol improves negative, affective and cognitive symptoms in chronic schizophrenia comparable to risperidone. Further studies should confirm the latter using neuropsychological performance tests and should investigate whether tolerability improves with a markedly lower dose range.

Neurobiological studies hypothesize a common final pathway of addictive behavior in the mesolimbic dopaminergic system. Nicotine has been shown to sensitize the reward pathway, thereby causing increased drug-seeking behavior. Since there is evidence to suggest that nicotine, alcohol and other psychoactive substances act on the same final pathway and seem to augment their effects in animal subjects, drug intake behavior of humans would likely be reflected in increased substance use of nicotine-dependent persons. We used biological markers of substance use as well as questionnaires to assess the levels of psychoactive substance use among 18-year-old males in a naturalistic cross-sectional setting. We found that increasing levels of nicotine dependence were related to higher levels of alcohol abuse and dependence. Furthermore, higher levels of nicotine dependence were associated with elevated levels of recent cannabinoid use.

Aims: Though glutamic acid is well known as a working excitatory in the CNS, its impact on the modulation of alcohol withdrawal symptoms and withdrawal fits are not yet clear. The study has been undertaken to examine the levels of glutamic acid in chronic alcohol-dependent patients at different stages of alcohol withdrawal and weaning and to examine any existence of any differences according to Cloninger's and Lesch's typologies., Patients and Methods: One hundred and fifty-nine alcohol-dependent patients were assessed according to Cloninger's and Lesch's typologies and related to abstinence duration, age, and gender. Blood samples were taken for mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT) and glutamic acid, in order to find primarily any differences in glutamic acid according to the typologies, age, abstinence duration, and liver damage., Results: There was no significant association between Cloninger's and Lesch's typologies. Cloninger's types 1 and 2 had an equal distribution of GGT and duration of abstinence, while Lesch's type I had more patients with high GGT, and more patients who were sober for a maximum of 2 days. Unlike in Lesch's types, glutamic acid levels did not differ according to Cloninger's types, as significantly higher glutamic acid values were found in Lesch's types I and IV. Glutamic acid values did not differ significantly in different age groups., Conclusions: Our study findings of varying glutamic acid levels seen in Lesch's typology, higher in types I and IV than in types II and III, are of significant clinical value and can be interpreted differently, as in type I high levels of glutamic acid is seen as a kindling phenomenon, while in type IV elevated levels might be related to either compulsivity of frequent repetition of drinking or withdrawal.

Background: Biological markers for chronic alcohol consumption like MCV or gammaGT or carbohydrate deficient transferrin (CDT) are useful, but far from being perfect. In patients with liver disease a reliable marker for chronic alcohol consumption as the underlying etiology is highly needed. Recently, a new ELISA based version of the carbohydrate-deficient-transferrin (CDT-TRISIALO (-)) assay has been developed, which measures asialo-, monosialo- and disialo transferrin, but excludes trisialo- transferrin; that modification suggests higher sensitivity and specificity in detecting recent alcohol consumption in patients., Aims: The study goal was to evaluate the sensitivity, specificity, positive and negative predicitive value of this new carbohydrate-deficient-transferrin assay (CDT-TRISIALO (-)) in a group of patients with liver disease and to compare the results with that of the established CDT assay (CDT-TRISIALO (+))., Patients and Methods: Our study population consisted of 110 consecutive patients (male: n = 80 [72.7 %], female: n = 30 [27.3 %]) with liver disease of the following etiologies: chronic alcohol consumption (n = 51 [46.4 %]; Out of them 30 alcohol abusing patients were assessed by cage = 1 and 21 alcohol dependent patients were assessed by cage = 2, chronic viral hepatitis (n = 33 [30.0 %]) including 25 [22.7 %] patients with chronic hepatitis C infection and 8 [7.3 %] patients with chronic hepatitis B infection), haemochromatosis (n = 4 [3.6 %]), mechanical cholestasis (n = 17 [15.5 %]) and other liver diseases (n = 5 [4.6 %] including autoimmune hepatitis (n = 2) and primary biliary cirrhosis (n = 3)). 27.3 % of our patients (n = 30) had no liver cirrhosis whereas the majority (72.7 %, n = 80) had liver cirrhosis., Results: In our population of liver disease patients the CDT-TRISIALO (-) assay had a sensitivity of 72.7 % and specificity of 58.1 % for recent alcohol consumption at the published cutoff level of 2.6 %. The positive predictive value was 34.0 % and the negative predictive value was 87.8 %. Sensitivity and specificity of the CDT-TRISIALO (+) assay at the recommended cutoff level of 4.7 % were similar, 77.3 % and 49.3 %, respectively. The positive and negative predictive values were 30.9 % and 88.1 %. CDTTRISIALO (+) and CDT-TRISIALO (-) levels increased significantly with higher Child-Pugh stages., Conclusion: The newly developed carbohydrate deficient transferrin test (CDT-TRISIALO (-)) is of no advantage as compared to the established assay (CDT-TRISIALO (+)) when used in a patient population with liver disease. In that population, normal CDT-TRISIALO (-) helps to exclude recent alcohol consumption; this results from the high negative predictive value of a normal CDT-TRISIALO (-).

Aims: To assess recent drug use through urine testing as well as the prevalence of tobacco and alcohol dependence among young males and to analyse the associations between tobacco dependence and cannabis use (delta-9-tetrahydrocannabinol, THC), tobacco dependence, and alcohol dependence as well as between THC use and other illicit drug use., Methods: Urine samples were collected, and nicotine and alcohol questionnaires were administered. Carbon monoxide was assessed in exhaled air. Data from young males from representative, selected districts of Lower Austria were recorded during the annual physical examination for mandatory military service. Out of all 18-year-old males in Austria 3.8% (n = 1902) were included in the study. Prevalence of recent illicit drug use, tobacco dependence (heavy smoking index, HSI), alcohol dependence (The 4-item cutting down, annoyance by criticism, guilty feeling, and eye-openers (CAGE) questionnaire), and associations between substance categories by means of logistic regression analyses were calculated., Results: Alcohol abuse was found in 15.1% and alcohol dependence was found in 3.2%. According to the HSI 51.5% of males reported daily smoking, of whom 43.7% showed a mild level, and 7.8% a high level, of nicotine dependence. About 5.1% of the sample evidenced THC in urine. Opiates were identified in 2.7% of urine samples. Smokers showed a higher risk of THC use. THC users had a tendency to use cocaine and amphetamines more frequently than THC abstainers., Conclusion: Nicotine and alcohol dependence is common among young males. Biological assessment of illicit drug use seems to confirm previous questionnaire-based findings of associations between THC use and other illicit drugs. Urine testing seems to be an adequate method to analyse associations of THC use and other illicit drugs. In combination with questionnaires urine testing may be used for the assessment of associations of tobacco dependence and recent illicit drug use based on epidemiological surveys.

The aim of this study was to investigate the analgesic effects of hypnotic pain control on experimental pain by measuring pupil reactions as an objective psycho-physiologic parameter. Twenty-two healthy volunteers (11 female and 11 male) aged between 22 and 35 years participated in the study. Pupil diameter was measured as baseline measurement (i.e., static measurement) in the non-hypnotic and in the hypnotic state. Pupil diameter changes to a standardized pain stimulus were measured in the non-hypnotic and hypnotic state and compared. Additionally, a Fourier analysis of pupil oscillations reflecting central nervous activation during the static measurement (25.6 sec) was calculated. During the hypnotic state the pain related pupil dilation was significantly smaller than during the non-hypnotic state. Pupil oscillations were significantly reduced during hypnosis.

Purpose: In this cross-sectional study we compared alcohol-dependent smokers and non-alcohol-dependent smokers with respect to intensity of nicotine dependence, craving conditions, sleep disturbances, comorbidity with major depression, reasons for smoking, accompanying somatic diseases and patients' prolonged abstinence from smoking during the 3 years preceding the study., Subjects and Methods: Fifty-one alcohol-dependent smokers and 327 non-alcohol-dependent smokers diagnosed as ICD-10 and DSM-IV-nicotine dependent, were investigated by means of the Fagerström Test for Nicotine Dependence, the Lübeck Craving-Recurrence Risk Questionnaire and the Lesch Alcohol Dependence Typology (both adapted to smoking)., Results: The intensity of nicotine dependence was more enhanced in alcohol-dependent smokers compared to non-alcohol-dependent smokers. Several variables of all factors of craving ("depressive mood", "stimulation", "relaxation", "socially triggered tension") were significantly increased in alcohol-dependent patients (P<0.05). Alcohol-dependent smokers showed depressive symptoms and sleep disturbances, whilst non-alcohol-dependent individuals mainly smoked for stress release and weight control., Discussion: Our study demonstrates that the intensity of nicotine dependence, several conditions of craving for nicotine, sleep disturbances and symptoms of depression appear to be enhanced in alcohol-dependent smokers compared with non-alcohol-dependent smokers. Conclusions. - It is hoped that the factors of craving and reasons for smoking identified in this study will contribute to a better understanding of smoking temptation in alcohol-dependent smokers and non-alcohol-dependent smokers in future.

Human substance use is complex, being influenced by many psychopathological and sociological factors as well as the substance's pharmacological effects. Dependence development is not attributable directly to the consumed substance, but takes also all the other issues into regard. One of all these issues might be that gender represents an influencing factor and impacts on tolerance of a substance, on abuse patterns and finally on development of dependence as well as on addiction related disorders. Therapeutic programs' needs might be different too. In general, more men than women are alcohol dependent or have alcohol problems, but women are at greater risk for adverse effects and alcohol related diseases. Death rates among female alcoholics are 50 to 100 percent higher than those of men. Major impairments, diagnosis, medical and psychosocial consequences and their implication on treatment will be outlined.

Carbohydrate-deficient transferrin (CDT) has been well established as a marker for high alcohol consumption. As studies concerning the specificity of CDT in patients with liver disease have shown controversial outcomes, efforts to illuminate mechanisms leading to impaired CDT specificity in this patient group cannot yet be considered successful. Evidence of apoptosis as examined in 72 alcohol-dependent patients using serum contents of caspase-related M30 monoclonal antibody significantly correlated with aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase but did not influence CDT levels. These results suggest that impairment of CDT specificity is brought forth by derangement of hepatic metabolism rather than by acute hepatocellular damage.

Aims: Early clinical electroencephalographers reported that low-voltage fast desynchronized patterns were frequently seen in chronic alcoholism, suggesting hyperarousal of the central nervous system (CNS). The aim of the present study was to investigate the brain function of drug-free, detoxified alcoholics, and compare this with that of normal controls, utilizing computerized quantitative EEG analysis and subsequent EEG mapping. Moreover, differences between patients relapsing or abstaining during 6 months of relapse prevention therapy, pharmacologically supported by either flupentixol decanoate 10 mg or placebo i.m. every 2 weeks, were determined., Methods: 22 drug-free, detoxified patients (15 men, seven women) aged between 27 and 58 (mean 41.5 +/- 8.1) years, diagnosed as alcohol-dependent (ICD-10: F10.23) were included in the study. They were subdivided into abstainers (n = 11) and relapsers (n = 11), and matched with normal healthy controls according to age (mean 41.5 +/- 8.4 years) and sex. A 3-min vigilance-controlled EEG (V-EEG) was obtained and analysed off-line by multi-lead EEG power spectral analysis and subsequent mapping methods., Results: The drug-free, detoxified, alcohol-dependent patients showed, as compared with controls, aberrant brain function characterized by a decrease in delta and slow alpha and an increase in beta activity as well as an acceleration of the total centroid. These findings were more pronounced in relapsing than in abstaining patients. After 6 months of treatment, abstaining patients showed an increase in slow activity, a decrease in fast alpha, an acceleration of the delta/theta centroid and a deceleration of the alpha centroid, reflecting a normalization of brain function., Conclusion: EEG maps of alcohol-dependent patients differ significantly from those of normal controls and patients suffering from other mental disorders and thus EEG mapping may be used for diagnostic purposes. Moreover, the quantitative EEG may also be of prognostic value as relapsing patients differ from abstaining ones, since they show a significantly more pronounced hyperarousal of the CNS.

Background: The misconception of tobacco smoking as a 'bad habit' has been replaced by a diagnosis of addiction. Although help to quit is offered by nicotine replacement, antidepressants and psychotherapeutic support, there is no cure yet. One cause of impediment might be psychiatric comorbidity. Therefore, we searched for smoker subgroups, needing different treatments., Aim of the Study: The study aimed at subtyping smokers in an attempt to better understand the phenomenon of resistant smokers and provide more information that could potentially become useful to treatment centres assuming the subtypes correlate directly with outcomes of different smoking cessation treatments, tailor-made according to subtypes., Methods: 330 out of 430 recruited smokers were classified as nicotine dependent (ICD-10) and tobacco dependent (DSM-IV) and remained in the study. They were investigated with different diagnostic assessments: Fagerström Test (FT), Lübeck Craving Risk Relapse Questionnaire and Lesch Typology Questionnaire (the last two being modified for smoking)., Results: Dependence severity degree is reflected by the FT. FT scores >/=5 indicated higher conspicuousness. Four clusters for nicotine craving were found: (1) 'depressed', (2) 'stimulated', (3) 'relaxed mood state' and (4) 'socially triggered tensed mood'. In contrast to alcoholism, 'stimulation' was one of the major craving conditions in smokers. The decision tree, consisting of the FT and the Lesch Typology Questionnaire, distinguishes four subgroups of nicotine-dependent persons., Conclusion: The subgroups reflect different reinforcement and psychosocial disturbances. They match treatment and can be applied as outcome predictors in controlled treatment and relapse prevention studies., (Copyright 2004 S. Karger AG, Basel)

A study recently finished by our research group elucidated the effectiveness of flupenthixol decanoate (FLX) in maintaining abstinence in detoxified alcoholics. Flupenthixol decanoate is an established antipsychotic drug, which is well known for its mild antidepressant and anxiolytic activity as well as for its minimal sedation at low doses. It blocks dopamine binding at a number of receptor subtypes, primarily at D-1, D-2, D-3 and with less affinity at D4-receptors. It also affects serotonin binding at 5-HT2A and 5-HT2C receptors. In a double-blind placebo-controlled multicenter trial, 77 women and 204 men suffering from moderate or severe DSM-II-R alcohol dependence were randomly assigned to either 10 mg FLX or placebo both injected every second week over a period of 24 weeks (treatment phase) succeeded by a medication-free 24-weeks follow-up period. In the overall analysis the number of patients relapsed after 24 weeks of treatment (=main criterion of efficacy) was significantly higher in the FLX treated group (85.2%) than under placebo (65.5%). However, when differentiating this result according to sex the analysis revealed a gender-related discrepancy: while male patients had an almost 4-fold higher risk to relapse under FLX than under placebo (OR=3.95) this risk was barely elevated for female patients (OR=1.51). A significantly negative outcome due to FLX treatment was restricted to male alcoholics solely. In conclusion, gender-related differences to pharmacological relapse prevention with FLX have probably contributed to a better treatment outcome in women than in men.

Alcohol abuse and alcoholism cut across gender, race and nationality. In general, more men than women are alcohol dependent or have alcohol problems, but women are at greater risk for adverse effects and alcohol-related diseases. Death rates among female alcoholics are 50 to 100 percent higher than those of men. Major physiological impairments, the diagnostic distribution, the psychosocial consequences and their implication on treatment will be outlined.

The efficacy of flupentixol and risperidone were compared in a randomized double-blind study in 153 chronic schizophrenic patients. Flupentixol showed to be not inferior to risperidone concerning schizophrenic negative symptoms at week 8, 16 and 24. Positive symptoms and general psychopathology improved comparably, too. There was a trend in favor of flupentixol concerning the improvement of depressive symptoms and a trend in favor of risperidone concerning the improvement of preexisting parkinsonian symptoms. The study data justify to regard flupentixol as a "partial atypical" antipsychotic.

The efficacy of flupentixol and risperidone were compared in a randomized double-blind study in 153 chronic schizophrenic patients. Flupentixol showed to be not inferior to risperidone concerning schizophrenic negative symptoms at week 8, 16 and 24. Positive symptoms and general psychopathology improved comparably, too. There was a trend in favor of flupentixol concerning the improvement of depressive symptoms and a trend in favor of risperidone concerning the improvement of preexisting parkinsonian symptoms. The study data justify to regard flupentixol as a "partial atypical" antipsychotic.