barcelona . spain - European Association for the Study of the Liver

BARCELONA . SPAIN
80 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 81
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012
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MANAGEMENT OF ALCOHOL DEPENDENCE IN PATIENTS WITH ALD
Giovanni Addolorato
Rome, Italy
E-mail: g.addolorato@rm.unicatt.it
KEY POINTS
• In patients with alcohol liver disease (ALD), persistent alcohol intake is associated with disease
progression, therefore the most effective recommendation for these individuals is total alcohol
abstinence.
• In alcohol dependent patients, disulfiram, naltrexone and acamprosate, combined with
counseling, represent effective medications in reducing alcohol consumption and preventing
relapse and they are both approved for this indication. It should kept in mind that naltrexone
and disulfiram are not recommended in patients with ALD and that there are no data on the
safety of acamprosate in patients with ALD.
• Topiramate and baclofen may represent potential novel alcohol pharmacotherapies, but they are
not approved for this indication. To date, baclofen represents the only alcohol pharmacotherapy
tested in alcoholics with ALD (i.e. alcohol-dependent patients with cirrhosis).
INTRODUCTION
Alcohol use disorders (alcohol abuse and dependence) is a chronic, relapsing condition with a multifactorial
etiology that includes genetic, neurobiological, psychological, and environmental components. Protracted
behaviour modification, cognitive behavioural therapy, psychological counseling, and mutual support
groups (eg, Alcoholic Anonymous) have been considered the most effective long-term treatments. However,
increasing knowledge of the neurobiological mechanisms underlying the development and persistence of
addiction has led to wider recognition of alcohol addiction as a clinical disorder. In particular, specific brain
neurotransmitter systems associated with alcohol craving and addiction have been identified. Accordingly,
treatment has progressed from social and behavioural approaches alone to ‘adjunct’ pharmacotherapy
interventions and since the 1980s, the number of medications found to be potentially effective in treating
alcohol craving and dependence has increased. In particular before the discovery of anti-craving drugs, the
administration of disulfiram and surveillance by relatives and/or therapeutic groups, waiting for spontaneous
craving exhaustion, were the only treatment strategies to control craving. In the last decades, several
drugs able to interfere with the neurotransmitters involved in craving mechanisms have been experimented
(Addolorato et al, Neuropsychobiology), showing their efficacy to increase abstinence and to prevent
relapse.
MAIN ANTI-CRAVING DRUGS
Naltrexone
Naltrexone is an opioid receptor antagonist. The use of naltrexone in alcohol-dependent patients is based
on the involvement of the opioid system in the compulsive desire for alcohol. In animal model, naltrexone
abolishes the alcohol deprivation effect demonstrating its anti-relapse properties and, consequently, its
anti-craving action. In humans, naltrexone, at a dose of 50 mg/day, has shown its efficacy in decreasing
the compulsive component of alcohol craving and in increasing the compliance to alcohol-detoxification
programs. A double-blind placebo-controlled study by Volpicelli et al.(1992) showed that the administration
of naltrexone to alcoholic patients decreases relapses by means of the reduction in the number of heavydrinking
days. Most studies found no significant difference in the occasional intake of alcohol (‘slips’) between
patients treated with naltrexone and with placebo; however, patients treated with naltrexone showed a
significantly lower percentage of full relapse compared with patients treated with placebo. Obviously, the
efficacy of the drug is increased when the treatment is combined with a specific psychological support, in