The European acamprosate trials: Conclusions for research and therapy

Lesch, Otto Michael; Riegler, Anita; Gutiérrez, Karin; Hertling, Inés; Ramskogler, Katrin; Semler, Brigitte; Zoghlami, Ali; Benda, Norbert; Walter, Henriëtte

doi:10.1007/bf02255976

Cited by 72 publications

(19 citation statements)

References 31 publications

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“…While data are consistent with repeated withdrawals (deprivations) increasing voluntary alcohol ingestion Rodd-Henricks et al 2000a,b, 2001 or bar pressing for alcohol , inconsistencies appear to exist between these latter findings and those obtained with models of alcohol motivation. Therefore, it would seem wise to undertake future investigations to resolve these apparent differences associated with voluntary alcohol drinking, self-administration of alcohol with bar pressing and models of alcohol-seeking behavior, particularly with respect to previous repeated deprivations from chronic alcohol exposure.…”

Section: Repeated Alcohol Withdrawals and The Alcohol-deprivation Effmentioning

confidence: 81%

“…Opiate antagonists (Heinälä et al 2001;Litten and Allen 1998;O'Malley et al 1992;Monti et al 2001;Rubio et al 2001;Volpicelli et al 1992), acamprosate (Ansoms et al 2000;Besson et al 1998;Chick et al 2000;Lesch et al 2001;Rubio et al 2001;Sass et al 1996;Tempesta et al 2000;Litten and Allen 1998; see overview by Mason 2001) or a combination of these drugs (Kranzler and Van Kirk 2001) are currently prescribed to reduce alcohol consumption in alcoholics. In preclinical studies, opiate antagonists are capable of minimizing acute drinking of alcohol (Altshuler et al 1980;Badia-Elder et al 1999;Froehlich et al 1990;Heyser et al 2003;Hölter and Spanagel 1999;Hyytia and Sinclair 1993;Overstreet et al 1999;Samson and Doyle 1985), as well as reducing alcohol seeking by an alcohol conditioned stimulus (Liu and Weiss 2002a;Koob et al 2003).…”

Section: Future Directionsmentioning

confidence: 99%

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Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

2004

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Rationale-The rationale for proposing the "kindling"/stress hypothesis is to provide a conceptual basis for the insidious development and maintenance of alcohol abuse.Objective and results-An objective of the hypothesis is to emphasize how continued alcohol abuse is linked to progressive neural adaptation. Work has shown that repeated withdrawals from chronic low levels of alcohol sensitize ("kindle") anxiety-like behavior ("anxiety") in rats, a finding consistent with multiple withdrawal kindling of seizure activity. Additionally, stress substitutes for initial cycles of the multiple withdrawal protocol to sensitize withdrawal-induced anxiety, which is indicative that stress is capable of facilitating neuroadaptive processes related to withdrawal. The persistence of adaptation caused by stress and multiple withdrawals is revealed by the appearance of withdrawal-induced anxiety following a future re-exposure to a single 5-day period of alcohol. This persisting adaptation also permits stress to induce anxiety during a period of abstinence-a response not observed in animals without previous exposure to alcohol. Furthermore, stress interacts with repeated withdrawals to enhance voluntary alcohol drinking. Results of other preclinical and clinical studies reported in the literature are integrated with these investigations in support of the proposed hypothesis.Conclusions-The "kindling"/stress hypothesis is based on the premise that repeated withdrawals from cycles of chronic alcohol exposure contribute to a progressive development of persisting adaptive change that sensitizes withdrawal-induced anxiety and allows stress to evoke symptoms associated with negative affect during abstinence. Thus, these consequences of repeated withdrawals account for the evolution of major characteristics of alcoholism, which include worsened acute withdrawal symptoms and increased stress-induced negative affect during abstinence, both of which enhance the likelihood of relapse-and with relapse an inability to limit an abusive pattern of alcohol intake. The "kindling"/stress hypothesis provides a clear strategy for future studies to explore the advancing neural adaptation proposed to contribute to the pathogenesis of alcoholism.

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Section: Repeated Alcohol Withdrawals and The Alcohol-deprivation Effmentioning

confidence: 81%

Section: Future Directionsmentioning

confidence: 99%

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

2004

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“…This longitudinal study verified and falsified individual items and thus filtrated criteria correlating with further illness course. Those criteria form the four subgroups of the Lesch alcoholism typology: a 'biological addiction' group with early and severe withdrawals (type I), an anxiety coping group (type II), a group with comorbidity (mainly depressive; type III) and a group with cognitive impairment prior to the development of alcoholism (type IV) [19][20][21][22][23][24]26]. The subgroups have been validated biologically and neurophysiologically [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

The Austrian Multicentre Study on Smoking: Subgroups of Nicotine Dependence and Their Craving

Lesch

Dvorak²,

Hertling³

et al. 2004

Neuropsychobiology

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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.

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“…Results of clinical studies testing the pharmacotherapy effects of acamprosate are very different. While some authors, especially in Europe, show clear efficacy, the opinions in the USA vary 66,67 . Thus, different effects of acamprosate were shown in various subtypes of alcoholism.…”

Section: Neuropharmacological Treatment Of Alcoholismmentioning

confidence: 99%

Neurobiological Bases of Alcohol Addiction

Matošić¹,

Marušić²,

Vidrih³

et al. 2016

ACC

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SUMMARY -Alcohol addiction is a heterogeneous psychiatric disorder according to both phenotype and etiology. Difference in phenotype characteristics manifests in the manner the addiction arises, history of the alcoholic and history of drinking, comorbid disorders, and the phenomenon of abstinence difficulties. Concerning the etiology of alcoholism, the disease itself is considered to be a consequence of an interactive influence of the environment and genetic factors. Numerous researches conducted in the last decades discovered many aspects of the biochemical, cell and molecular bases of alcohol addiction, leading to a conclusion that alcoholism is, like many other addictions, a brain disease. By recognizing alcoholism as a disease which basically implies changes of the neurobiological mechanisms, as well as a clear genetic basis, it was supposed that the disease, having its basis solely in the symptomatology, is essentially heterogeneous. By trying to solve the problem of a clinically heterogeneous nature of the disease during the last fifty years, various sub-classifications of such patients have been suggested. According to Cloninger, subtypes of alcoholism differ also according to changes in the brain neurotransmission systems, i.e. it is supposed that patients suffering from alcoholism type 1 have a more pronounced dopaminergic transmission deficit, while dopaminergic transmission is not disturbed significantly in patients diagnosed with alcoholism type 2, who, however, have a significant lack of serotonergic transmission. In such a way, Cloninger actually presented the basis of the so-called neurobiological alcoholism model. Since he has connected differences in neurotransmission with differences in personality characteristics, this model is also known as the psychobiological model of alcoholism. The characteristic of alcoholism type 1 is avoiding damage (Harm Avoidance, HA) decreased dopamine transmission and increased serotonin transmission, while the significant characteristic of alcoholism type 2 is seeking for excitement (Novelty Seeking, NS), unchanged dopamine transmission and decreased serotonin transmission. These neurochemical differences among alcoholism subtypes represent the basis for a different therapy approach. Intake of alcohol changes different gene expression in the human brain. The inheritance model of alcoholism is not fully explained, however, it is considered that the disease is connected to a larger gene number included in neurotransmission, cell mechanisms and general metabolic function, with a simultaneous influence of the environment. The contribution of genetic factors is stronger in certain types of alcoholism and thus we have been confronted in the last years of alcoholism research with studies researching the connections of some alcoholism subtypes with the polymorphism phenomenon in the genes coding the synaptic proteins included in the alcoholism etiology. The primary role of monoamine oxidase (MAO) in the brain is catalysis of deamination of the oxidative neurotransmitter a...

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The European acamprosate trials: Conclusions for research and therapy

Cited by 72 publications

References 31 publications

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

The Austrian Multicentre Study on Smoking: Subgroups of Nicotine Dependence and Their Craving

Neurobiological Bases of Alcohol Addiction

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