Second edition

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acamprosate, in patients with normal renal function, is given
in a dose of 666 mg three times daily; it appears that naltrexone
is more effective than acamprosate (Morley et al. 2006),
although the combination of naltrexone plus acamprosate
appears to be more effective than naltrexone alone (Kiefer
et al. 2003). Topiramate is used in total daily doses of approximately
100–200 mg (Johnson et al. 2003). Each one of these
three agents has been shown to reduce the number of drinking
days in patients who do ‘slip’ and drink, although the
overall results are modest at best. Disulfiram is begun in a
dose of 500 mg daily, with the dose reduced to 250 mg daily
after 1 or 2 weeks; patients should be given a graphic description
of the toxic reaction that they may expect should they
ingest even a miniscule amount of alcohol, and, given the
potential toxicity of disulfiram, treatment is generally maintained
for only a matter of months. Divalproex neither
reduces the urge to drink nor the intoxication that occurs
with drinking, but may, in doses similar to those used for
alcohol withdrawal, reduce lingering withdrawal symptomatology.
Choosing among these medications is not straightforward.
Out of naltrexone, acamprosate, and topiramate, all
other things being equal, it is probably reasonable to begin
with naltrexone. Given its toxicity, disulfiram should be
reserved for highly motivated patients. The place of divalproex
is not as yet clear; however, if it has been used during
treatment of alcohol withdrawal, and one can predict a lingering
withdrawal, it is reasonable to continue it.
Although these medications may be helpful, patients
must not be allowed to think that their use can substitute
for involvement in psychosocial treatments. Many patients
fondly hope for a ‘magic bullet’ that will resolve their alcoholism,
and such hopes must be firmly dashed. The overall
role of the physician in the treatment of alcoholism per se is
generally limited to treatment of some of the complications
of alcoholism (e.g., hepatic failure) and to treatment
of any concurrent disorders, such as depression, panic disorder,
or schizophrenia. As a general rule, in prescribing
medications for these or any other conditions, potentially
intoxicating drugs, such as benzodiazepines or opioids,
should be avoided as they may trigger off a desire to drink;
exceptions to this rule are few.
Alcoholism is a chronic disease and hence relapses are
to be expected; these occur most frequently in the first 6
months of treatment. Relapses, or ‘slips’, therefore,
although certainly undesirable, should not be taken as an
indication of failure but rather as an indication for patients
to redouble their efforts.
21.6 SEDATIVES, HYPNOTICS, AND
ANXIOLYTICS
The sedatives, hypnotics, and anxiolytics, including the
benzodiazepines and related drugs, comprise a large group
of agents, often collectively referred to as the ‘sedative–
hypnotics’, each of which has an effect similar to that of
alcohol. Although most commonly used in conjunction
21.6 Sedatives, hypnotics, and anxiolytics 667
with alcohol or other substances, such as opioids, stimulants
or cocaine, they may at times be used in isolation.
Table 21.1 lists these various agents, grouped according to
their half-lives, as short acting (generally less than 6 hours),
intermediate acting (6–18 hours) or long acting (generally
over 24 hours). This classification is useful as it allows one
to make a rough prediction as to when withdrawal, withdrawal
seizures, or withdrawal delirium is likely to occur.
The popularity of these various agents has changed over
time. The barbiturates, meprobamate, and chloral hydrate,
once commonly abused, have been supplanted by the benzodiazepines,
among which alprazolam, lorazepam, and
diazepam are most popular.
Clinical features
As indicated, the clinical features of sedative–hypnotic use
are similar to those of alcohol, and thus one may see sedative–hypnotic
intoxication, blackouts, tolerance, withdrawal,
withdrawal seizures, and withdrawal delirium.
Each of these is discussed below in turn.
When mild, sedative–hypnotic intoxication with barbiturates
(Curran 1938, 1944; Isbell et al. 1950), meprobamate
(Roache and Griffiths 1987), or benzodiazepines is
characterized by euphoria, a degree of affective lability, and
disinhibition. With moderate intoxication, reaction time is
slowed, lethargy and drowsiness appear, and patients often
develop nystagmus, dysarthria, and ataxia; falls may occur,
with possible head injury. With severe intoxication stupor
or coma may occur, with respiratory depression and death.
Sedative–hypnotic blackouts are quite similar to those
seen with alcohol; although possible with long-acting
Table 21.1 Sedative–hypnotics grouped by duration of effect
Short-acting (less than 6 hours) Triazolam
Alprazolam
Zolpidem
Zaleplon
Intermediate-acting (6–18 hours) Oxazepam
Temazepam
Lorazepam
Chlordiazepoxide
Meprobamate
Chloral hydrate
Long-acting (greater than 24 hours) Quazepam
Prazepam
Halazepam
Flurazepam
Clonazepam
Diazepam
Amobarbital
Secobarbital
Pentobarbital
Phenobarbital
Butalbital