Transcript Pharmacotherapy forAlcohol Dependence

Is There a Role for
Medications in the
Treatment of Alcohol
Dependence ?
Vania Modesto-Lowe, MD
Copyright Alcohol Medical Scholars Program
1
Where are treatment
efforts focused?
• Management of alcohol withdrawal
• Amelioration of comorbid psychiatric
condition
• Long-term treatment of alcoholism
Copyright Alcohol Medical Scholars Program
2
Myth or Reality ?
Recovery requires a
medication-free state
True or False?
Copyright Alcohol Medical Scholars Program
3
Medications for Relapse
Prevention in Alcoholics
Naltrexone (1994)
Disulfiram (1950)
Acamprosate (...)
Nalmefene (...)
Copyright Alcohol Medical Scholars Program
4
Neurotransmitters and
Alcohol Dependence
Dopamine
Opioids
Glutamate
GABA
Serotonin
Copyright Alcohol Medical Scholars Program
5
Disulfiram
Sensitizing agent
Mechanism of action
Efficacy ?
Copyright Alcohol Medical Scholars Program
6
Alcohol Dependence and
the Opioidergic System
Opioid agonists increase alcohol
consumption
Alcoholics have decreased serum Bendorphin levels
Copyright Alcohol Medical Scholars Program
7
Naltrexone for Alcohol
Dependence
Volpicelli et al. (1992)
O’Malley et al.. (1992)
12 week
12 week
70 veterans
97
Delayed first drink
Decreased relapse
Decreased craving
Similar findings
Copyright Alcohol Medical Scholars Program
8
Naltrexone Side-Effects
Nausea (10%)
Headache (7%)
Anxiety (2%)
Sedation (2%)
Insensitive to opioid analgesia
Copyright Alcohol Medical Scholars Program
9
Naltrexone Mechanism of
Action
Reinforcement
Craving
Aversive effects
Neuroendocrine
Copyright Alcohol Medical Scholars Program
10
Remaining Issues
Negative trials
Compliance
Dose/Duration/ Optimal candidates
Nalmefene
Copyright Alcohol Medical Scholars Program
11
Alcohol Dependence and
the Serotonergic System
Acute administration of alcohol
The neuropathology of 5-HT in alcohol
preferring animals
Copyright Alcohol Medical Scholars Program
12
5-HT and Human Alcohol
Consumption
Reduced 5-HIAA levels
SSRI’s
Copyright Alcohol Medical Scholars Program
13
Fluoxetine in Alcoholics
Transient reduction in drinking
Reduction in drinking in alcoholics with a
family history of Alcohol Dependence
Copyright Alcohol Medical Scholars Program
14
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
15
5-HT Trials to Reduce
Alcohol Use
Ritanserin
Odansetron
Buspirone
Copyright Alcohol Medical Scholars Program
16
SSRIs and “High Risk”
Alcoholics
Differential 5-HT activity in alcoholics
Alcohol subtypes
SSRI’s and type B alcoholics
Copyright Alcohol Medical Scholars Program
17
5-HT Medications for
Alcohol Dependence and
Comorbid Depression
Fluoxetine
Sertraline
Copyright Alcohol Medical Scholars Program
18
Acamprosate
Approved in Europe
Efficacy
GABA and Glutamate
Mechanism of action
Copyright Alcohol Medical Scholars Program
19
Advantages of
Acamprosate
Excreted by the kidneys
Mild side effect profile
Best documented efficacy
Copyright Alcohol Medical Scholars Program
20
Remaining Issues
Need to identify most responsive
subgroup
Results of multicenter trial pending
Copyright Alcohol Medical Scholars Program
21
Conclusions
Disulfiram
Opioid antagonists
Acamprosate
Copyright Alcohol Medical Scholars Program
22
Copyright Alcohol Medical Scholars Program
23