copyright alcohol medical scholars program1 is there a role for medications in the treatment of...
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Copyright Alcohol Medical Scholars Program 1
Is There a Role for Medications in the Treatment of Alcohol Dependence ?
Vania Modesto-Lowe, MD
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Where are treatment efforts focused?
•Management of alcohol withdrawal•Amelioration of comorbid
psychiatric condition•Long-term treatment of alcoholism
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Myth or Reality ?
Recovery requires a medication-free state
True or False?
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Medications for Relapse Prevention in Alcoholics
Naltrexone (1994)
Disulfiram (1950)
Acamprosate (...)
Nalmefene (...)
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Neurotransmitters and Alcohol Dependence
DopamineOpioidsGlutamate GABASerotonin
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Disulfiram
Sensitizing agent
Mechanism of action
Efficacy ?
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Alcohol Dependence and the Opioidergic System
Opioid agonists increase alcohol consumption
Alcoholics have decreased serum B-endorphin levels
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Naltrexone for Alcohol Dependence
Volpicelli et al. (1992)
12 week
70 veterans
Delayed first drinkDecreased relapseDecreased craving
O’Malley et al.. (1992)
12 week
97
Similar findings
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Naltrexone Side-Effects
Nausea (10%)
Headache (7%)
Anxiety (2%)
Sedation (2%)
Insensitive to opioid analgesia
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Naltrexone Mechanism of Action
Reinforcement
Craving
Aversive effects
Neuroendocrine
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Remaining Issues
Negative trials
Compliance
Dose/Duration/ Optimal candidates
Nalmefene
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Alcohol Dependence and the Serotonergic System
Acute administration of alcohol
The neuropathology of 5-HT in alcohol preferring animals
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5-HT and Human Alcohol Consumption
Reduced 5-HIAA levels
SSRI’s
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Fluoxetine in Alcoholics
Transient reduction in drinking
Reduction in drinking in alcoholics with a family history of Alcohol Dependence
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Fluoxetine in Alcoholics
Kranzler et al. (1995) found no overall advantage on drinking outcomes
Kabel and Petty (1996) showed no effect among alcohol-dependent veterans
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5-HT Trials to Reduce Alcohol Use
Ritanserin
Odansetron
Buspirone
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SSRIs and “High Risk” Alcoholics
Differential 5-HT activity in alcoholics
Alcohol subtypes
SSRI’s and type B alcoholics
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5-HT Medications for Alcohol Dependence and Comorbid Depression
Fluoxetine
Sertraline
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Acamprosate
Approved in Europe
Efficacy
GABA and Glutamate
Mechanism of action
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Advantages of Acamprosate
Excreted by the kidneys
Mild side effect profile
Best documented efficacy
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Remaining Issues
Need to identify most responsive subgroup
Results of multicenter trial pending
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Conclusions
Disulfiram
Opioid antagonists
Acamprosate
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