Drugs for Relapse Prevention of Alcoholism

Contents

List of contributors

Preface

History of prevention of relapse

Why history?

Punishment as the earliest form of relapse prevention

Salvation as prevention of drunken relapse

Treatment makes its entry as means to prevent the drunken relapse

Relapse prevention as a psychological undertaking

Relapse prevention as physical treatment

Alcoholics anonymous as agent of relapse prevention

Conclusions and directions for the future

References

How to measure relapse in animals

Introduction

The reinstatement model

The alcohol deprivation effect model

References

How to measure relapse in humans

Introduction

Outcome measures in alcohol treatment trials

Methods used to collect drinking data in alcohol treatment trials

Alcohol pharmacotherapy trials

Outcome measures for alcohol treatment trials: future directions

References

Disulfiram (Antabuse®): the first medication to stop drinking

Introduction

Randomized open efficacy study

Conclusions

References

Naltrexone: preclinical data

Introduction

Dosage

Acquisition and reinstatement of ethanol seeking behavior

Specificity of action

Combination pharmacotherapy

Other interactions of naltrexone and ethanol

Conclusions

References

Naltrexone: clinical data

History

The first naltrexone study in alcoholics

Clinical trials

Heterogeneity in alcoholism

Adherence to the medication regimen

Pharmacology of naltrexone

Anti-craving effect

Psychotherapy

Genetics

Medication side effects

Selection of patients

References

Acamprosate: preclinical data

Introduction

Animal studies – general characterization

Attenuation of ethanol intake and relapse

Involvement of the glutamatergic system in the action of acamprosate

Acamprosate and taurine

Conclusion

References

Acamprosate: clinical data

Development and first testing

Pharmacology of acamprosate

Randomized controlled studies in patients

Cost – effectiveness

Combining acamprosate and other medications

Acamprosate and psychotherapy

Conclusions and perspectives

References

Serotonergic compounds: preclinical data

Introduction

5-HT receptor types and subtypes in alcohol consumption

5-HT and relapse to alcohol

Animal models of relapse to alcohol

Conclusions

References

Serotonergic compounds: clinical data

Introduction

Selective serotonin reuptake inhibitors

5- HT1 partial agonists

5- HT2 antagonists

5- HT3 antagonists

Other 5-HT receptor subtypes

Conclusions

References

Opioidergic compounds: preclinical data

Introduction

Effects of selective

receptor antagonists on ethanol consumption

Effects of selective

receptor antagonists on ethanol consumption

Effects of selective opioid receptor antagonists on ethanol seeking

Opioidergic mechanisms of ethanol reinforcement and conditioned ethanol effects

References

Second generation opioidergic compounds: clinical data

Introduction

Pharmacokinetics

Hepatic toxicity

Blocking opioid effects

Hormonal effects

Eating

Flushing and acetaldehyde

Clinical trials of nalmefene in alcoholism treatment

Newer clinical results

Relapse: definition of terms

Conclusions

References

Dopaminergic compounds: preclinical data

Introduction

Evidence implicating dopamine neurotransmission as a target for relapse prevention

Manipulation of dopamine receptors and ethanol-seeking behavior

Is dopamine neurotransmission a promising treatment target?

Effects of indirect manipulation of dopamine transmission on ethanolseeking

References

Dopaminergic compounds: clinical data

Introduction

Lisuride

Tiapride

Bromocriptine

Flupenthixol

References

Baclofen: preclinical data

Introduction

Effect of GABAB receptor agonists on alcohol intake and alcohol motivational properties in rats

Effect of GABAB receptor agonists on relapse- like behaviors in rats

References

Baclofen: clinical data

Introduction

Baclofen in alcohol dependence: relapse prevention

Alcohol withdrawal syndrome

Baclofen in other substance dependence

References

Cannabinoid receptor antagonists: a perspective

Introduction

Effect of SR 141716 on relapse-like behavior in alcohol-preferring rats

Effect of the combination of SR 141716 plus naloxone on relapse-like behavior in alcohol- preferring rats

References

Neuropeptide Y antagonists: a perspective

Introduction

Basic biology of the central NPY system

NPY in EtOH-responses and EtOH seeking behavior

NPY, alcoholism and human genetics

NPY and alcoholism: pharmacological mechanisms and strategies

NPY and alcohol: conclusions and future directions

References

Glutamatergic compounds: a perspective

Introduction

Substances acting at ionotropic glutamate receptors (iGluR)

Substances acting at metabotropic glutamate receptors (mGluR)

Conclusions

References

Future perspectives on relapse prevention

Harm reduction in combination with substitution therapy

Pharmacotherapy in combination with behavioral and psychosocial therapy ( COMBINE)

Individual adapted pharmacotherapy (PREDICT): improving clinical efficacy

Involvement of the pharmaceutical industry in bridging the gap between the academic world and alcoholic patients

Educational programs for improving the clinical and social “climate” for pharmacological relapse prevention

Conclusion

References

Appendix – Chemical structures

Index