Copyright Alcohol Medical Scholars Program 1
Is There a Role for Medications in the Treatment of Alcohol Dependence ?
Vania Modesto-Lowe, MD
Copyright Alcohol Medical Scholars Program 2
Where are treatment efforts focused?
•Management of alcohol withdrawal•Amelioration of comorbid
psychiatric condition•Long-term treatment of alcoholism
Copyright Alcohol Medical Scholars Program 3
Myth or Reality ?
Recovery requires a medication-free state
True or False?
Copyright Alcohol Medical Scholars Program 4
Medications for Relapse Prevention in Alcoholics
Naltrexone (1994)
Disulfiram (1950)
Acamprosate (...)
Nalmefene (...)
Copyright Alcohol Medical Scholars Program 5
Neurotransmitters and Alcohol Dependence
DopamineOpioidsGlutamate GABASerotonin
Copyright Alcohol Medical Scholars Program 6
Disulfiram
Sensitizing agent
Mechanism of action
Efficacy ?
Copyright Alcohol Medical Scholars Program 7
Alcohol Dependence and the Opioidergic System
Opioid agonists increase alcohol consumption
Alcoholics have decreased serum B-endorphin levels
Copyright Alcohol Medical Scholars Program 8
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
Copyright Alcohol Medical Scholars Program 9
Naltrexone Side-Effects
Nausea (10%)
Headache (7%)
Anxiety (2%)
Sedation (2%)
Insensitive to opioid analgesia
Copyright Alcohol Medical Scholars Program 10
Naltrexone Mechanism of Action
Reinforcement
Craving
Aversive effects
Neuroendocrine
Copyright Alcohol Medical Scholars Program 11
Remaining Issues
Negative trials
Compliance
Dose/Duration/ Optimal candidates
Nalmefene
Copyright Alcohol Medical Scholars Program 12
Alcohol Dependence and the Serotonergic System
Acute administration of alcohol
The neuropathology of 5-HT in alcohol preferring animals
Copyright Alcohol Medical Scholars Program 13
5-HT and Human Alcohol Consumption
Reduced 5-HIAA levels
SSRI’s
Copyright Alcohol Medical Scholars Program 14
Fluoxetine in Alcoholics
Transient reduction in drinking
Reduction in drinking in alcoholics with a family history of Alcohol Dependence
Copyright Alcohol Medical Scholars Program 15
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
Copyright Alcohol Medical Scholars Program 16
5-HT Trials to Reduce Alcohol Use
Ritanserin
Odansetron
Buspirone
Copyright Alcohol Medical Scholars Program 17
SSRIs and “High Risk” Alcoholics
Differential 5-HT activity in alcoholics
Alcohol subtypes
SSRI’s and type B alcoholics
Copyright Alcohol Medical Scholars Program 18
5-HT Medications for Alcohol Dependence and Comorbid Depression
Fluoxetine
Sertraline
Copyright Alcohol Medical Scholars Program 19
Acamprosate
Approved in Europe
Efficacy
GABA and Glutamate
Mechanism of action
Copyright Alcohol Medical Scholars Program 20
Advantages of Acamprosate
Excreted by the kidneys
Mild side effect profile
Best documented efficacy
Copyright Alcohol Medical Scholars Program 21
Remaining Issues
Need to identify most responsive subgroup
Results of multicenter trial pending