Drugs for Relapse Prevention of Alcoholism (eBook)

Contents 6
List of contributors 8
Preface 11
History of prevention of relapse 13
Why history? 13
Punishment as the earliest form of relapse prevention 13
Salvation as prevention of drunken relapse 15
Treatment makes its entry as means to prevent the drunken relapse 16
Relapse prevention as a psychological undertaking 17
Relapse prevention as physical treatment 18
Alcoholics anonymous as agent of relapse prevention 19
Conclusions and directions for the future 20
References 22
How to measure relapse in animals 24
Introduction 24
The reinstatement model 24
The alcohol deprivation effect model 27
References 31
How to measure relapse in humans 33
Introduction 33
Outcome measures in alcohol treatment trials 34
Methods used to collect drinking data in alcohol treatment trials 35
Alcohol pharmacotherapy trials 40
Outcome measures for alcohol treatment trials: future directions 44
References 46
Disulfiram (Antabuse®): the first medication to stop drinking 50
Introduction 50
Randomized open efficacy study 51
Conclusions 55
References 56
Naltrexone: preclinical data 58
Introduction 58
Dosage 58
Acquisition and reinstatement of ethanol seeking behavior 60
Specificity of action 61
Combination pharmacotherapy 62
Other interactions of naltrexone and ethanol 62
Conclusions 63
References 63
Naltrexone: clinical data 68
History 68
The first naltrexone study in alcoholics 69
Clinical trials 71
Heterogeneity in alcoholism 72
Adherence to the medication regimen 74
Pharmacology of naltrexone 75
Anti-craving effect 75
Psychotherapy 76
Genetics 76
Medication side effects 77
Selection of patients 78
References 79
Acamprosate: preclinical data 82
Introduction 82
Animal studies – general characterization 82
Attenuation of ethanol intake and relapse 83
Involvement of the glutamatergic system in the action of acamprosate 84
Acamprosate and taurine 85
Conclusion 89
References 90
Acamprosate: clinical data 93
Development and first testing 93
Pharmacology of acamprosate 94
Randomized controlled studies in patients 94
Cost – effectiveness 97
Combining acamprosate and other medications 98
Acamprosate and psychotherapy 99
Conclusions and perspectives 99
References 100
Serotonergic compounds: preclinical data 102
Introduction 102
5-HT receptor types and subtypes in alcohol consumption 103
5-HT and relapse to alcohol 108
Animal models of relapse to alcohol 109
Conclusions 109
References 110
Serotonergic compounds: clinical data 114
Introduction 114
Selective serotonin reuptake inhibitors 114
5- HT1 partial agonists 116
5- HT2 antagonists 117
5- HT3 antagonists 117
Other 5-HT receptor subtypes 119
Conclusions 119
References 120
Opioidergic compounds: preclinical data 124
Introduction 124
Effects of selective 125
receptor antagonists on ethanol consumption 125
Effects of selective 126
receptor antagonists on ethanol consumption 126
Effects of selective opioid receptor antagonists on ethanol seeking 127
Opioidergic mechanisms of ethanol reinforcement and conditioned ethanol effects 128
References 129
Second generation opioidergic compounds: clinical data 132
Introduction 132
Pharmacokinetics 132
Hepatic toxicity 134
Blocking opioid effects 134
Hormonal effects 135
Eating 135
Flushing and acetaldehyde 135
Clinical trials of nalmefene in alcoholism treatment 136
Newer clinical results 137
Relapse: definition of terms 139
Conclusions 139
References 140
Dopaminergic compounds: preclinical data 142
Introduction 142
Evidence implicating dopamine neurotransmission as a target for relapse prevention 142
Manipulation of dopamine receptors and ethanol-seeking behavior 145
Is dopamine neurotransmission a promising treatment target? 153
Effects of indirect manipulation of dopamine transmission on ethanolseeking 154
References 155
Dopaminergic compounds: clinical data 161
Introduction 161
Lisuride 162
Tiapride 163
Bromocriptine 163
Flupenthixol 165
References 166
Baclofen: preclinical data 168
Introduction 168
Effect of GABAB receptor agonists on alcohol intake and alcohol motivational properties in rats 168
Effect of GABAB receptor agonists on relapse- like behaviors in rats 172
References 174
Baclofen: clinical data 176
Introduction 176
Baclofen in alcohol dependence: relapse prevention 176
Alcohol withdrawal syndrome 180
Baclofen in other substance dependence 181
References 183
Cannabinoid receptor antagonists: a perspective 186
Introduction 186
Effect of SR 141716 on relapse-like behavior in alcohol-preferring rats 187
Effect of the combination of SR 141716 plus naloxone on relapse-like behavior in alcohol- preferring rats 189
References 190
Neuropeptide Y antagonists: a perspective 193
Introduction 193
Basic biology of the central NPY system 193
NPY in EtOH-responses and EtOH seeking behavior 195
NPY, alcoholism and human genetics 199
NPY and alcoholism: pharmacological mechanisms and strategies 200
NPY and alcohol: conclusions and future directions 202
References 203
Glutamatergic compounds: a perspective 208
Introduction 208
Substances acting at ionotropic glutamate receptors (iGluR) 209
Substances acting at metabotropic glutamate receptors (mGluR) 215
Conclusions 216
References 217
Future perspectives on relapse prevention 220
Harm reduction in combination with substitution therapy 220
Pharmacotherapy in combination with behavioral and psychosocial therapy ( COMBINE) 224
Individual adapted pharmacotherapy (PREDICT): improving clinical efficacy 224
Involvement of the pharmaceutical industry in bridging the gap between the academic world and alcoholic patients 225
Educational programs for improving the clinical and social “climate” for pharmacological relapse prevention 227
Conclusion 228
References 228
Appendix – Chemical structures 230
Index 241