[Psychosocial Treatment of Addictive Disorders--An Overview of Psychotherapeutic Options and their Efficacy]. / Psychosoziale Behandlungen bei Suchterkrankungen--Suchtspezifische Psychotherapieformen und ihre Wirksamkeit.

Addictive disorders are chronic relapsing conditions marked by compulsive and often uncontrolled use of psychotropic substances or stimuli. In this review, we present and discuss the current specific psychosocial interventions for addictive disorders and their effectiveness. In particular cognitive behavioral therapy, motivational interviewing, relapse prevention, the community reinforcement approach, and contingency management were found to be effective. For these psychotherapeutic treatments, mostly moderate effect sizes have been found. Their effectiveness seems to be highest in cannabis dependence. Empirical evidence for dependence on "hard" drugs is largest for contingency management, while for alcohol dependence motivational interviewing and the community reinforcement approach show the largest effect sizes. Presumably, combinations of different approaches as well as online interventions will bring further progress in the psychosocial treatment of addictive disorders in the future.

Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution.

Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.

Cognitive behavioral smoking cessation during alcohol detoxification treatment: a randomized, controlled trial.

BACKGROUND: Among alcohol-dependent subjects tobacco smoking is very common and causes a variety of health risks. Therefore, it is necessary to reach this high-risk population early with appropriate smoking interventions. METHODS: Smokers in alcohol detoxification treatment were offered to participate in a smoking cessation study. A total of 103 patients was enrolled and randomly assigned to either the experimental group (EG) receiving a cognitive behavioral smoking cessation treatment (CBT) or the control group (CG) receiving autogenic training. Smoking outcomes were measured by self-report and carbon monoxide levels, directly after intervention and 6 months later, where additionally alcohol outcomes were recorded. RESULTS: There were no differences in smoking quit rates directly after intervention. However, patients in the EG were significantly more likely to reduce their daily cigarette use compared to CG (p=.046). Sub-group analyses revealed that heavy smokers (FTND score ≥ 7) seemed to profit most in the EG regarding cigarette reduction. After 6 months, these positive effects had leveled out. No evidence was found that smoking cessation might jeopardize alcohol outcomes. CONCLUSIONS: Results suggest that alcohol-dependent smokers are interested in smoking interventions even during alcohol detoxification. CBT is promising in short-term smoking outcomes and in the approach of harm reduction, however, long-term effects are desirable. These findings underline the feasibility and the importance to provide smoking cessation interventions to patients in alcohol detoxification treatments.

[Alcohol and violence: a current review]. / Alkohol und Gewalt: Eine aktuelle Übersicht.

Violent behaviour under the influence of alcohol is a long-known phenomenon and causes great suffering in affected persons and enormous costs for society. While earlier studies considered alcohol-associated violence primarily to be due to alcohol's disinhibiting effects, recent scientific studies show a complex interaction of various bio-psycho-social factors. Including recent study results, the following review presents current data on the epidemiology of alcohol-associated violence, discusses possible contributing factors and causes, and possible resulting therapeutic implications. Based on these results, populations at risk such as binge drinkers, young adults and individuals with substance use disorders and comorbid psychiatric disorders can be identified, who often display a high burden of problems and therefore need a close network of medical, psychiatric and social services.

Pilot study of the application of magnetic bead protein profiling to the study of biomarkers in addiction research.

OBJECTIVES: Proteomic technologies based on mass spectrometry are increasingly used as a valuable tool in clinical research allowing high-throughput protein and peptide profiling to be undertaken. Whilst previous research has focussed the application of this novel technology on the study of patients with disorders compared to comparable individuals from the healthy population, this current study seeks to determine the effect of successful treatment for alcoholism on the serum protein profile obtained. METHODS: Serum samples were collected from patients after initial treatment for alcohol abuse and also 6 months after treatment. The serum samples were prepared for analysis using reverse phase magnetic bead fractionation and the resulting peptides analysed by matrix assisted laser desorption ionisation time-of-flight (MALDI-ToF) mass spectrometry. RESULTS: Whilst the majority of the peptides detected by this approach exhibited constant levels between the two time points, three peptides were elevated at the 6-month time point compared to the initial sampling. CONCLUSIONS: Whilst disorders with very clear biological causes (such as cancer) exhibit significantly different peptide profiles, psychiatric disorders such as alcohol addiction which are multifactorial show less obvious changes. Despite this the two groups of samples could statistically be distinguished by certain peptides expression levels.

Tobacco smoking and depression--results from the WHO/ISBRA study.

AIMS: To elucidate the relationship between tobacco smoking and depression, and to estimate the impact of other substance dependencies. DESIGN: Cross-sectional. PARTICIPANTS: A total of 1,849 men and women were interviewed face-to-face using a validated structured questionnaire. According to their tobacco smoking behavior, participants were grouped into never smokers, ex-smokers and current smokers. MEASUREMENTS: Data were generated through the WHO/ISBRA study, an international multicenter study with a cross-sectional design. A standardized questionnaire was administered face-to-face by trained interviewers. Logistic regression analysis was used to predict depression. RESULTS: There was a significant difference across the 3 smoking groups in the number of subjects who had major depression (DSM-IV) during their lifetime. The highest rate of depressives was found in current smokers (23.7%), the lowest rate in never smokers (6.2%), while the rate of those who had quit smoking (14.6%) was between both. In a logistic regression analysis, alcohol dependence (both current and during lifetime) as well as cocaine dependence were significant predictors of depression. However, the association between smoking and depression still remained statistically significant. CONCLUSIONS: This study adds support to the evidence that smoking is linked to depression. It also elucidates the importance of taking into account alcohol and cocaine dependence since they have a significant impact on the relationship between smoking and depression.

The impact of self-help group attendance on relapse rates after alcohol detoxification in a controlled study.

AIMS: Self-help groups such as Alcoholics Anonymous (AA) are widely recommended for aftercare of alcohol-dependent persons, even though scientific knowledge of its effectiveness is inconsistent. The aim of the present analysis was to elucidate whether persons attending AA groups regularly after detoxification have lower relapse rates within 1 year, compared to persons without self-help group attendance. METHODS: Data for the present analysis were derived from the placebo-group of a multi-centre study in Germany (Wiesbeck et al., 2001). Patients were free to choose either self-help group attendance (N = 50) or no support (N = 28). RESULTS: After 1-month of follow-up, there was a lower relapse rate in patients attending a self-help group as compared to the control group, a difference, however, that leveled off during the following months. Moreover, relapse rates did not differ significantly at any point of time between both groups. Levels of social functioning improved in both groups over 1 year. CONCLUSIONS: The present study was unable to show an advantage of self-help group attendance in reducing relapses compared to the control group.

[Psychosocial stress and alcohol consumption: interrelations, consequences and interventions]. / Psychosozialer Stress und Alkoholkonsum: Wechselwirkungen, Krankheitsprozess und Interventionsmöglichkeiten.

BACKGROUND: Psychosocial stress can not only be considered as a result of chronic alcohol abuse, but also as a cause of high alcohol consumption and it maintains as a distress syndrome the subsequent course of the alcohol use disorder. METHODS: This review summarises empirical research results concerning the interrelations between psychosocial stress and alcohol consumption. The effects of psychosocial stress are regarded as an ideal-typical process leading to an increased alcohol intake and later to chronic alcohol abuse, often ending in alcohol dependence. The aim of the study is to demonstrate the relevance of stress and distress for diagnostics and therapy of alcohol- related disorders. RESULTS: At the starting point of high alcohol consumption psychological relief due to the stress-reducing effects of alcohol is often assumed. A vicious circle begins, perpetuating psychosocial distress and reinforcing the anxious or depressive symptoms related to emerging distress syndromes. Associated frequent comorbidities during the progression are other substance- related disorders, anxiety and affective disorders. Following alcohol dependence severe somatic and psychosocial consequences have to be anticipated. CONCLUSIONS: Psychosocial stress, distress and psychological effects can be understood as an important psychopathological developmental process of prolonged alcoholism. Symptoms of distress may be a first relevant evidence of high and hazardous alcohol consumption. Alcoholic patients should be motivated early to attend psychiatric and psychotherapeutic treatments to improve their chances for a positive development. Positive results can be achieved with stress management programs in alcohol dependent patients. These interventions appear to have comparable effects to other treatments.

The candidate gene approach in alcoholism: are there gender-specific differences?

It is well established that genetic factors play a major role in the development of alcoholism in both sexes. Several twin studies demonstrated a nearly equally high magnitude of genetic influence for men and women. However, the genetic sources of vulnerability are supposed to only partially overlap in men and women. Therefore, we evaluated the gender-specific effects of two single nucleotide polymorphisms affecting dopaminergic neurotransmission (dopamine D2 receptor: -141C Ins/Del polymorphism; Dopamine D3 receptor: Bal I) in our large sample of primary alcoholics. Only a gender-specific analysis of subgroups with a putatively high genetic load, e.g., family-history-positive or presence of severe withdrawal complications, revealed significant differences in allele-/genotype-frequency. Our results demonstrate that a varying sex distribution in the samples investigated might contribute to the heterogeneous results reported in association studies for candidate genes in alcoholism and, therefore, should be taken into account in future studies.

Gender and personality in alcoholism.

The topic gender and personality in alcoholism is discussed on the background of a research project on clinical aspects of alcoholism at the University of Würzburg, Germany. The data of this study are presented in the context of two questions: Which personality differences are there between women and men dependent on alcohol, and is there a connection between these personality differences and features of the alcohol dependence? Additionally, we take a look at gender-related differences in the development of alcoholism. In a first step, gender differences in the development and the course of alcoholism are investigated. The data revealed only weak differences between female and male alcoholics when important confounding variables like age and education are taken into consideration. Secondly, the female and male alcoholics are matched according to age and education and their personality structures are compared by using several well-established and standardized self-report questionnaires. No serious gender differences concerning the main characteristics of alcohol dependence could be discovered. However, some remarkable personality differences between female and male alcoholics are found: women scored significantly higher on Neuroticism and Harm-Avoidance while men reached significantly higher scores on Venturesomeness and Sensation-Seeking. In order to detect a possible connection between alcoholism and gender-related personality differences, both males and females are subdivided into two groups using the scores of Neuroticism, Harm-Avoidance, Venturesomeness and Sensation-Seeking, respectively. We have found no indication for a gender-specific relevance of personality differences between female and male alcoholics with regard to Harm-Avoidance, Venturesomeness or Sensation-Seeking. However, differences in Neuroticism have revealed a greater relevance in alcohol-dependent women than in men.

Gender-related differences in pharmacological relapse prevention with flupenthixol decanoate in detoxified alcoholics.

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.

Dopamine D2 (DAD2) and dopamine D3 (DAD3) receptor gene polymorphisms and treatment outcome in alcohol dependence.

The dopaminergic system is critically involved in reward mechanisms mediating the reinforcing effects of alcohol. The intention of this study was to investigate the genotypic frequencies of the -141C Ins/Del polymorphism of the DAD2 receptor gene as well as the Bal I polymorphism of the DAD3 receptor and their potential association with treatment outcome in alcoholism. Therefore, individuals suffering from primary alcohol dependence were clinically and genetically characterized and followed prospectively over a period of one year after inpatient treatment. No association was found between DAD2 or DAD3 receptor gene variants and treatment outcome as reflected by abstinence/relapse after one year. Taking into account potential stratification effects, such as family history, gender, age of onset, or severity of the disease an association with DAD2 or DAD3 gene variants could neither be found. In conclusion, we found no evidence that the DAD2 or DAD3 gene variants investigated have a major influence on treatment outcome in primary alcohol dependence.

Alcohol cue-reactivity in heavy and light social drinkers as revealed by event-related potentials.

An elevated cue-reactivity evoked by alcohol-related stimuli (cues) in alcohol-dependent patients has been described for different physiological variables, including electrophysiological measures, such as event-related potentials (ERPs). Cue-reactivity has, however, also been reported for social drinkers. The aim of this study is to assess the effect of the drinking behaviours of social drinkers on cue-reactivity as measured with ERPs. Forty alcohol-related and 40 neutral pictures were presented to 15 heavy and 15 light drinkers (all males). ERPs were recorded using 21 scalp electrodes. Stimuli were presented for 500 ms with an inter-stimulus interval of 2000 ms. Heavy social drinkers displayed a cue-reactivity of significantly higher amplitude at the frontal electrode location Fz, elicited by alcohol-related, as compared to neutral, pictures. This effect was not found in light social drinkers. The results indicate that the cue-reactivity previously found in alcohol-dependent patients is also present in social drinkers, and that electrophysiological cue-reactivity is associated with alcohol consumption.

Neuroendocrine responses to fenfluramine and its relationship to personality in alcoholism.

This study investigates the relationship between personality and serotonergic reactivity in alcohol dependence. Personality characteristics were assessed according to the Temperament and Character model of Cloninger, the five-factor model of McCrae and Costa, Zuckerman's Sensation Seeking as well as Eysenck's impulsiveness/venturesomeness. Placebo-controlled prolactin response to the serotonin (5-HT) reuptake inhibitor/releaser fenfluramine served as an indicator for the reactivity of serotonergic neurotransmission. Forty abstinent alcohol-dependent men were subdivided into high and low prolactin responders according to their level of neuroendocrine response. High responders were characterized by decreased harm avoidance while their extraversion and venturesomeness scores were increased in comparison to low responders. The data demonstrates that harm avoidance on the one hand and extraversion/venturesomeness on the other are inversely correlated to serotonergic neurotransmission. These results support a specific relationship between personality traits and the serotonergic system.

Flupenthixol decanoate and relapse prevention in alcoholics: results from a placebo-controlled study.

Flupenthixol, with its broad receptor profile, interacts with a variety of dopamine and serotonin binding sites which are important in the neurobiology of alcohol dependence. Its pharmacology, together with encouraging results from both animal studies and clinical trials with cocaine users, led us to postulate that flupenthixol would significantly prevent relapse in detoxified alcohol-dependent individuals. We conducted a prospective, randomized, double-blind, placebo-controlled, multi-centre trial with two parallel groups and appropriate statistical evaluation. Subjects met criteria for moderate to severe alcohol dependence (DSM-III-R), without any concomitant psychiatric disorder. After complete detoxification, 281 women and men received either 10 mg of flupenthixol decanoate or placebo as i.m. injection every second week for 6 months on an out-patient basis, followed by 6 months of follow-up. Efficacy was based on absolute abstinence, with relapse being defined as consumption of any alcohol after inclusion in the study. In contrast to the hypothesis, flupenthixol did not reduce, but was associated with more, relapses. Though well tolerated, relapse rates after 6 months of treatment were 85.2% (flupenthixol) versus 65.5% (placebo), a highly significant difference from the medication. Flupenthixol was also inferior to placebo with regard to other secondary criteria of efficacy (cumulative abstinence duration, relapse rate after 12 months). These results indicate that a 10 mg dose of flupenthixol decanoate does not have a beneficial effect on abstinence maintenance in alcohol-dependent individuals.

Pharmacological relapse prevention in alcohol dependence: from animal models to clinical trials.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Jobst August-Ludwig Boening and Otto Michel Lesch. The presentations were (1) Pharmacological validation of a new animal model of alcoholism, by Rainer Spanagel; (2) Persisting loss of control as main criterion for alcohol addiction in rats and mice, by Jochen Wolffgramm; (3) Role of NMDA receptor subunits associated with protein kinase C in the prevention of alcohol dependence, by Minoru Narita; (4) Long-term follow up of continued naltrexone treatment, by David Sinclair; (5) Pharmacological treatment trials with dopaminergic and serotonergic substances: Myths or facts? by Gerhard A. Wiesbeck; and (6) Methodology and behavioral therapy of the U.S. acamprosate study, by Barbara J. Mason.

Event-related potentials and cue-reactivity in alcoholism.

BACKGROUND: Relapse is a major problem in the treatment of addictive behaviors. Conditioning models of alcohol addiction suggest that stimuli associated with previous drug use (cues) may initiate relapse in a definite group of alcoholics. Event-related potentials (ERPs) might be useful to reveal the brain functional substrates of cue-reactivity. METHODS: In a preliminary investigation, 11 alcohol-dependent patients who did not take part in the electrophysiological study completed a structured interview to rate 80 words as to the degree of relatedness to alcohol. Based on these results, cue-reactivity for 15 alcohol-related and 15 unrelated word cues, each repeated eight times, was investigated in 19 alcohol-dependent men (44.2 +/- 8.5 years) and 19 healthy control men (42.5 +/- 12.5 years). RESULTS: A cue-reactivity that consisted of significantly higher amplitudes in the ERPs after alcohol-related words compared with unrelated words was found in alcohol-dependent patients, but not in controls, at the electrode location Pz [F(1,36) = 5.2,p < 0.05]. CONCLUSIONS: Consistent with the hypothesis, only alcohol-dependent patients were characterized by signs of increased cerebral activity associated with alcohol-related compared with unrelated cues. Therefore, the results support the concept of cue-reactivity in alcoholism based on a neurobiological measurement. Future investigations will show whether this cue-reactivity can be applied to assess the risk of relapse in individual alcohol-dependent patients.

Craving for alcohol and dopamine receptor sensitivity in alcohol-dependent men and control subjects.

Detoxified alcohol-dependent men and control subjects were repetitively exposed by sight and smell to either a neutral cue (tea) or an alcohol-related cue (their favourite alcoholic beverage) to provoke a maximum craving response. Additionally, their dopamine receptor sensitivity was evaluated by measuring growth hormone (HGH) response to stimulation with the dopamine receptor agonist apomorphine (APO). It was hypothesized that the subjects' desire to drink (craving) is related to their dopaminergic activity. In both groups, craving increased in the presence of the alcohol stimulus with significantly higher craving scores in alcoholics than in controls. However, in none of the groups and at no cue exposure did the craving response correlate with the individuals' dopaminergic activity as reflected by HGH release. Therefore, this study cannot add support to the hypothesis that craving for alcohol is associated with dopamine receptor sensitivity in abstinent alcoholics or healthy control subjects.