TREATMENT OF ALCOHOLISM
detoxification, psychosocial therapy either in intensive inpa-tient or in
outpatient rehabilitation programs serves as the primary treatment for alcohol
dependence. Other psychiatric problems, most commonly depressive or anxiety
disorders, often coexist with alcoholism and, if untreated, can contribute to
the tendency of detoxified alcoholics to relapse. Treatment for these
associated disorders with counseling and drugs can help decrease the rate of
relapse for alcoholic patients.
drugs—disulfiram, naltrexone, and acamprosate—have FDA approval for adjunctive
treatment of alcohol dependence.
a relatively long-acting opioid antagonist, blocks the effects at μ opioid
receptors . Studies in experi-mental animals first suggested a link between
alcohol consump-tion and opioids. Injection of small amounts of opioids was
followed by an increase in alcohol drinking, whereas adminis-tration of opioid
antagonists inhibited self-administration of alcohol.Naltrexone, both alone and
in combination with behavioral counseling, has been shown in a number of
short-term (12- to 16-week) placebo-controlled trials to reduce the rate of
relapse to either drinking or alcohol dependence and to reduce craving for
alcohol, especially in patients with high rates of naltrexone adher-ence.
Naltrexone was approved in 1994 by the FDA for treatment of alcohol
dependence.Naltrexone is generally taken once a day in an oral dose of 50 mg
for treatment of alcoholism. An extended-release formula-tion administered as
an IM injection once every 4 weeks is also effective. The drug can cause
dose-dependent hepatotoxicity and should be used with caution in patients with
evidence of mild abnormalities in serum aminotransferase activity. The
combina-tion of naltrexone plus disulfiram should be avoided, since both drugs
are potential hepatotoxins. Administration of naltrexone to patients who are
physically dependent on opioids precipitates an acute withdrawal syndrome, so
patients must be opioid-free before initiating naltrexone therapy. Naltrexone
also blocks the therapeu-tic analgesic effects of usual doses of opioids.
has been used in Europe for a number of years to treat alcohol dependence and
was approved for this use by the FDA in 2004. Like ethanol, acamprosate has
many molecular effects including actions on GABA, glutamate, serotonergic,
noradrenergic, and dopaminergic receptors. Probably its best-characterized
actions are as a weak NMDA-receptor antagonist and a GABAA-receptor
activator. In European clinical trials, acam-prosate reduced short-term and
long-term (more than 6 months) relapse rates when combined with psychotherapy.
In a large American trial that compared acamprosate with naltrexone and with
combined acamprosate and naltrexone therapy (the COMBINE study), acamprosate
did not show a statistically sig-nificant effect alone or in combination with
is administered as 1–2 enteric-coated 333 mg tablets three times daily. It is
poorly absorbed, and food reduces its absorption even further. Acamprosate is
widely distributed and is eliminated renally. It does not appear to participate
in drug-drug interactions. The most common adverse effects are gastrointestinal
(nausea, vomiting, diarrhea) and rash. It should not be used in patients with
severe renal impairment.
causes extreme discomfort in patients who drink alco-holic beverages.
Disulfiram alone has little effect; however, flush-ing, throbbing headache,
nausea, vomiting, sweating, hypotension, and confusion occur within a few
minutes after an individual tak-ing disulfiram drinks alcohol. The effects may
last 30 minutes in mild cases or several hours in severe ones. Disulfiram acts
by inhibiting aldehyde dehydrogenase. Thus, alcohol is metabolized as usual,
but acetaldehyde accumulates.
is rapidly and completely absorbed from the gastro-intestinal tract; however, a
period of 12 hours is required for its full action. Its elimination rate is
slow, so that its action may persist for several days after the last dose. The
drug inhibits the metabolismof many other therapeutic agents, including
phenytoin, oral anti-coagulants, and isoniazid. It should not be administered
with medications that contain alcohol, including nonprescription medications
such as those listed in Table 63–3. Disulfiram can cause small increases in
liver function tests. Its safety in pregnancy has not been demonstrated.
adherence to disulfiram therapy is low and because the evidence from clinical
trials for its effectiveness is weak, disulfiram is no longer commonly used.
other drugs have shown efficacy in maintaining abstinence and reducing craving
in chronic alcoholism, although none has FDA approval yet for this use. Such
drugs include ondansetron, a serotonin 5-HT3-receptor antagonist;
topi-ramate, a drug used for partial and generalized tonic-clonic sei-zures ;
and baclofen, a GABA B receptor antagonist used as a spasmolytic .
Based on evidence from model systems, efforts are underway to explore agents
that modu-late cannabinoid CB1 receptors, corticotropin-releasing factor
receptors, and GABA receptor systems, as well as several other possible
targets. Rimonabant, a CB1 receptor antagonist, has been shown to suppress
alcohol-related behaviors in animal models and is being tested in clinical
trials of alcoholism.