Download Management of Withdrawal Syndromes and Relapse Prevention in

Management of Withdrawal
Syndromes and Relapse
Prevention in Drug and Alcohol
Dependence
NORMAN S. MILLER, M.D.,
University of Illinois College of Medicine,
Chicago, Illinois
MARK S. GOLD, M.D.,
University of Florida Brain Institute,
Gainesville, Florida
The primary care physician is in a good position to diagnose,
manage and intervene with patients who are undergoing the
process of treatment and recovery from alcohol and drug
disorders. Medications such as benzodiazepines are effective in
the treatment of withdrawal syndromes, and naltrexone and
disulfiram can be used to augment relapse prevention. Patients
may also participate in psychosocial methods of addiction
treatment that can reduce the risk of relapse and improve their
psychosocial, health, legal and employment status.
Nearly one half of the patients who visit a family practice have an
alcohol or drug disorder. Primary care physicians have an opportunity to
intervene at all stages during the course of addictive illness. Each stage
can be characterized by types and severity of withdrawal and relapse
prevention.1-3 Management of alcohol and drug disorders includes
assessment, intervention, prescription of medications, participation in
specific addiction treatment strategies and monitoring of recovery.
Pharmacotherapy for
Withdrawal Syndromes
Detoxification
Pharmacologic therapies are indicated
for use in patients with addictive
disorders to prevent life-threatening
withdrawal complications such as
seizures and delirium tremens, and to
increase compliance with psychosocial
forms of addiction treatment.
Laboratory testing is indicated to
In treating alcohol withdrawal,
the longer-acting
benzodiazepines provide a
smoother transition to
abstinence than shorteracting preparations.
assess the type and timing of drugs used addictively and to guide
management of withdrawal and recovery.4
Alcohol
Management of alcohol withdrawal is based on the patient's history and
current clinical status. The single best predictor of the likelihood of future
withdrawal symptoms when alcohol is concerned is the patient's previous
history, e.g., the presence or absence of seizures or delirium tremens
(Table 1).
TABLE 1
Signs and Symptoms of Alcohol and Drug Withdrawal
Drug
Peak
period Duration Signs
Symptoms
Alcohol
1 to 3
days
5 to 7
days
Elevated blood
pressure, pulse and
temperature,
hyperarousal,
agitation,
restlessness,
cutaneous flushing,
tremors, diaphoresis,
dilated pupils, ataxia,
clouding of
consciousness,
disorientation
Anxiety, panic,
paranoid
delusions,
illusions, visual
and auditory
hallucinations
(often derogatory
and intimidating)
Benzodiazepines
and other
sedative/hypnotics
Shortacting:
2 to 4
days
Longacting:
4 to 7
days
Shortacting:
4 to 7
days
Longacting:
7 to 14
days
Increased
psychomotor activity,
agitation, muscular
weakness,
tremulousness,
hyperpyrexia,
diaphoresis, delirium,
convulsions, elevated
blood pressure, pulse
and temperature,
tremor of eyelids,
tongue and hands
Anxiety,
depression,
euphoria,
incoherent
thoughts, hostility,
grandiosity,
disorientation,
tactile, auditory
and visual
hallucinations,
suicidal thoughts
Stimulants
(cocaine,
amphetamines and
derivatives)
1 to 3
days
5 to 7
days
Social withdrawal,
psychomotor
retardation,
hypersomnia,
hyperphagia
Depression,
anhedonia,
suicidal thoughts
and behavior,
paranoid
delusions
Opiates (heroin)
1 to 3
days
5 to 7
days
Drug seeking,
mydriasis,
piloerection,
diaphoresis,
rhinorrhea,
lacrimation, diarrhea,
insomnia, elevated
blood pressure and
pulse (mild)
Intense desire for
drugs, muscle
cramps, arthralgia,
anxiety, nausea,
vomiting, malaise
PCP/psychedelics
Days
to
weeks
Days to
weeks
Hyperactivity,
increased pain
threshold, nystagmus,
hyperreflexia,
hypertension and
tachycardia, eyelid
retraction (stare),
agitation and
hyperarousal, dry and
erythematous skin,
violent and selfdestructive behaviors
Anxiety,
depression,
delusions, auditory
and visual
hallucinations,
memory loss,
irritable and angry
mood and affect,
suicidal thoughts
PCP=phencyclidine.
Alcohol withdrawal may be treated with a pharmacologic agent that
exhibits cross-tolerance with alcohol. Agents that are commonly
recommended include diazepam (Valium), lorazepam (Ativan),
chlordiazepoxide (Limbitrol), clorazepate (Tranxeme) and phenobarbital.
The usual initial dosage of diazepam or lorazepam is titrated according to
elevations of blood pressure, pulse rate, degree of agitation and presence
of delirium. In general, longer-acting preparations such as diazepam or
chlordiazepoxide provide a smoother and safer withdrawal than other
preparations. Shorter-acting preparations such as lorazepam are indicated
when elimination time for benzodiazepines is prolonged, such as in
patients with significant liver disease.
A loading dose of a long-acting benzodiazepine such as diazepam or
chlordiazepoxide may be given initially, and the dosage may then be
tapered. This method is often used in conjunction with a scale for
detoxification. It is also used frequently in an inpatient setting. The
physician should screen the patient for the presence of other sedating
drugs to avoid untoward drug interactions, particularly oversedation.
Initial loading doses for diazepam are in the range of 30 to 50 mg.
Suggested parameters and dosages are presented in Table 2.
TABLE 2
Medications for Alcohol Detoxification
Mild withdrawal
Diazepam (Valium),
5 to 10 mg orally as
needed
or
Lorazepam
(Ativan), 1 to 2 mg
orally every 4 to 6
hours as needed
for 1 to 3 days
Moderate
withdrawal
Severe
withdrawal
(delirium
tremens)*
Loading-dose
method
Diazepam:
15 to 20 mg orally
four times daily
on day 1
10 to 20 mg orally
four times daily
on day 2
5 to 15 mg orally
four times daily
on day 3
10 mg orally four
times daily on
day 4
5 mg orally four
times daily on
day 5
or
Lorazepam:
2 to 4 mg orally
four times daily
on days 1 and 2
1 to 2 mg orally
four times daily
on days 3 and 4
1 mg orally twice
daily on day 5
Diazepam, 10 to
25 mg orally as
needed every
hour while awake
until sedation
occurs
or
Lorazepam, 1 to 2
mg intravenously
as needed every
hour while awake
for 3 to 5 days (to
sedate)
Diazepam, 10 mg, or
chlordiazepoxide
(Limbitrol), 25 mg,
orally every hour
Diazepam may be
given intravenously
Systolic blood
pressure:
> 150 mm Hg
Systolic blood
pressure: 150 to
200 mm Hg
Systolic blood pressure: > 200 mm Hg
Diastolic blood
pressure: > 90 mm
Hg
Diastolic blood
pressure: 100 to
140 mm Hg
Diastolic blood pressure: > 140 mm Hg
Pulse: > 100
Pulse: 110 to 140 Pulse: > 140
Temperature:
>37.7°C (100°F)
Temperature:
37.7°C to 38.3°C
Administer
medication when:
Temperature: > 38.3°C (101°F)
(100°F to 101°F)
Tremulousness,
insomnia, agitation
are present
Tremulousness,
insomnia,
agitation are
present
Tremulousness, insomnia, agitation are
present
*--Monitoring in an intensive care unit is recommended for cardiac and respiratory function,
fluid and nutrition replacement, vital signs and mental status. Restraints are indicated in
patients who are confused or agitated to protect the patient from self and others (delirium
tremens can be a terrifying and life-threatening state). Thiamine, 100 mg intramuscularly or
orally every day for 3 to 7 days, hydration and magnesium replacement may be indicated,
according to the severity of the withdrawal state.5,6,10,21
Benzodiazepines and Other Sedative/Hypnotics
The signs and symptoms of benzodiazepine withdrawal are similar to
those for withdrawal of other sedative/hypnotics (barbiturates,
ethchylorvynol [Placidyl], glutethimide and meprobamate [Equanil])
(Table 1). The management of withdrawal for sedative/hypnotics
(barbiturates) is similar to that for benzodiazepines (Table 3).
Withdrawal from
benzodiazepines is not
usually marked by significant
elevations in blood pressure
and pulse as commonly occur
in patients undergoing
alcohol withdrawal.
Furthermore, supplemental
doses of sedatives taken as
needed are usually not
required for changes in vital
signs5-8 (Table 3). Since
benzodiazepines have crosstolerance within that drug
class as well as with other
sedative/hypnotic drugs,
benzodiazepines can be
substituted for other
sedative/hypnotics and vice
versa. Equivalent doses can
be calculated if the actual
doses are known before
beginning the tapering
process (Table 4).
A long-acting
benzodiazepine is more
effective than short-acting
preparations in suppressing
withdrawal symptoms and in
producing a gradual and
smooth transition to the
abstinent state. In general,
greater patient compliance
and lower morbidity can be
expected with the use of the
longer-acting
benzodiazepines, since
withdrawal symptoms are
less intense.
TABLE 3
Benzodiazepine (Barbiturate)
Withdrawal
Short-acting
detoxification
Long-acting
detoxification
7- to 10-day taper:
On day 1, give
diazepam (Valium),
10 to 20 mg orally
four times daily, and
taper until the
dosage is 5 to 10 mg
orally on last day.
Avoid giving the drug
"as needed."
Adjustments in
dosage according to
the patient's clinical
state may be
indicated.
10- to 14-day taper:
On day 1, give
diazepam, 10 to 20
mg orally four times
daily, and taper until
the dosage is 5 to 10
mg orally on last
day. Avoid giving the
drug "as needed".
Adjustments in
dosage according to
the patient's clinical
state may be
indicated.
or
or
7- to 10-day taper:
Calculate barbiturate
or benzodiazepine
equivalence and
give 50 percent of
the original dosage;
taper (if actual
dosage is known
before
detoxification). Avoid
giving the drug "as
needed."
10- to 14-day taper:
Calculate barbiturate
or benzodiazepine
equivalence and
give 50 percent of
the original dosage;
taper (if actual
dosage is known
before
detoxification). Avoid
giving the drug "as
needed."
Information from references 5 through 8.
A taper over eight to 12 weeks or longer may be indicated in patients who
have been taking benzodiazepines for several years (Table 5). The rate of
taper can be adjusted according to patient tolerance. The rate of taper is a
reduction in dosage of approximately 25 percent per quarter of the
withdrawal period (e.g., 25 percent per week for one month).
Stimulants (Cocaine, Amphetamines and Derivatives)
Supportive rather than specific treatment is indicated in patients who are
undergoing withdrawal from stimulants. Observation and monitoring for
depression and suicidal ideation are advised (Table 1). Since stimulant
withdrawal may cause significant irritability, a dosage of 5 to 10 mg of
diazepam given orally every six hours on a fixed schedule or as needed for
two to three days is recommended in patients with mild to moderate
withdrawal symptoms. For severe withdrawal symptoms with persistent
depression, therapy may be initiated with antidepressants such as
desipramine (Norpramin), at a dosage of 50 mg per day, titrated upward
every other day in 50-mg increments until a dosage of 150 to 250 mg per
day is attained. The dosage is maintained for three to six months and
discontinued by gradually tapering the drug over two weeks.4,9 However,
desipramine is not recommended routinely for management of withdrawal.
TABLE 4
Drug Dose Conversion* (Equivalent to 60 mg of Diazepam
[Valium] and 180 mg of Phenobarbital)
Drug
Dose
(mg)
Diazepam
(60 mg)
conversion
factor
Phenobarbital
(180 mg)
conversion
factor
6
150
24
90
240
12
60
60
10.0
0.4
2.5
0.6
0.25
5.0
1.0
1.0
30.0
1.2
7.5
2.0
0.75
15.0
3.0
3.0
600
600
600
180
0.1
0.1
0.1
0.33
0.3
0.3
0.3
1.0
2,400
0.025
0.075
Benzodiazepines
Alprazolam (Xanax)
Chlordiazepoxide
(Limbitrol)
Clonazepam (Klonopin)
Flurazepam (Dalmane)
Halazepam (Paxipam)
Lorazepam (Ativan)
Oxazepam (Serax)
Temazepam (Restoril)
Barbiturates
Butabarbital (Butisol)
Pentobarbital
(Nembutal)
Secobarbital (Seconal)
Phenobarbital
Glycerol
Meprobamate (Equanil)
Piperideinedione
Glutethimide (Doriden)
1,500
0.04
0.12
1,800
0.03
0.1
Quinazoline
Methaqualone
NOTE: To find the dose of chlordiazepoxide equivalent to that of diazepam, multiply by 0.4.
A dose of 150 mg of chlordiazepoxide is equivalent to a dose of 60 mg of diazepam. A dose
of 100 mg is equivalent to a dose of 40 mg, etc.
*--Conversion factor 3 dose=diazepam or phenobarbital dose equivalent. Divide this amount
in half to determine starting dosage.
Opiates
Withdrawal symptoms from heroin addiction are predictable and
identifiable (Table 1). Management of withdrawal can be accomplished
with clonidine (Catapres) or methadone. Patients for whom clonidine is
indicated include intranasal heroin users, outpatients and those who are
motivated to achieve abstinency. Patients for whom methadone is
indicated include intravenous users, inpatients, those who have medical
and psychiatric complications and patients with a history of poor
compliance when withdrawing from opiates5,9,10 (Table 6). Federal
regulations do not allow the use of methadone for detoxification if opiate
withdrawal is the primary diagnosis. However, methadone may be used if
the primary diagnosis is a medical condition and the secondary condition
is withdrawal from opiates.
Phencyclidine and Other Psychedelic Agents
Acute symptoms of withdrawal from psychedelic agents may be
diminished or reversed by using therapy with haloperidol (Haldol), 5 to 10
mg intramuscularly or orally every three to six hours as tolerated and
needed for behavior control. Lorazepam, 1 to 2 mg intravenously, or
diazepam, 5 to 10 mg orally every three to six hours, can also be given as
needed. Behavior control may also be indicated (e.g., isolation and
restraints).5,9,11
Medications for Relapse
Prevention
Disulfiram
Disulfiram is a major aversive
agent. It has been shown in a
randomized, double-blind,
placebo-controlled multisite trial12
to be effective as an adjunct to
other forms of addiction
treatment.
The key components to effective
use of disulfiram are overall
patient motivation for abstinence
and expectation of adverse
reactions. Selected patients who
have a commitment to working
with other treatments for
alcoholism may benefit from the
addition of disulfiram therapy.
The usual dosage of disulfiram is
250 mg per day, or 125 mg per
day in patients who experience
side effects such as sedation,
sexual dysfunction and elevated
liver enzymes.12,13
TABLE 5
Benzodiazepine Taper
Day
Dosage per day (mg)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10 mg three times daily=30 mg
10 mg three times daily=30 mg
10 mg three times daily=30 mg
5 mg four times daily=20 mg
5 mg four times daily=20 mg
5 mg four times daily=20 mg
5 mg three times daily=15 mg
5 mg three times daily=15 mg
5 mg three times daily=15 mg
5 mg twice daily=10 mg
5 mg twice daily=10 mg
5 mg twice daily=10 mg
5 mg every day=5 mg
5 mg every day=5 mg
5 mg every day=5 mg
Example: Patient taking 12 mg of
lorazepam (Ativan) per day=60 mg
diazepam (Valium) 3 (50 percent
reduction)=30 mg.
Disulfiram inhibits acetaldehyde dehydrogenase, an enzyme that catalyzes
the degradation of acetaldehyde (formed by the action of alcohol
dehydrogenase on alcohol). An accumulation of acetaldehyde produces an
unpleasant reaction when alcohol is consumed that is similar to a severe
hangover. It is potentially lethal, although only a small number of fatalities
have been reported. The reaction to disulfiram is characterized by
headache, diaphoresis, tachycardia, nausea and vomiting, cardiovascular
collapse, delirium, seizures and, occasionally, death. Before using
disulfiram, patients must have a blood alcohol level of zero and must be
able to comprehend the risks and benefits of treatment.12,13
Methadone
Methadone maintenance is a form of pharmacologic management of
opiate addiction. Methadone maintenance is performed in programs that
are in compliance with federal regulations. Patients must meet admission
requirements and must conform to clinic standards to participate in the
program. Typically, methadone is given daily in oral doses ranging from
30 to 100 mg or greater. Methadone is administered under the supervision
of a physician. Studies of methadone maintenance show initial efficacy
following entrance to the program, and the medication remains effective in
conjunction with other psychosocial forms of addiction treatment.
Moreover, some studies show a reduction in intravenous drug use as well
as in the rate of tests positive for human immunodeficiency virus
infection.5,9,14
Methadone is an opiate agonist that acts competitively at opiate receptor
sites to produce effects similar to those of other forms of opioids, such as
heroin. Methadone is itself addicting, and patients commonly relapse to
use of other drugs such as cocaine, alcohol, benzodiazepines and heroin.
Nonetheless, methadone maintenance can be an alternative for patients
who are addicted to intravenous heroin, particularly those who cannot or
will not accept an abstinence-based addiction treatment program.5,9,14
TABLE 6
Opiate Detoxification (Heroin/Morphine Withdrawal)
Clonidine (Catapres) substitution
Methadone substitution
Clonidine, 0.1 or 0.2 mg orally, given
every 4 to 6 hours as needed for
signs and symptoms of withdrawal
for 5 to 7 days. (Peak dosages are
given between 2 and 4 days.) Check
blood pressure before each dose
and do not give medication if patient
is hypotensive.
Methadone test dose of 10 mg given orally in
liquid or crushed tablet. Additional 10- to 20mg doses are given for signs and symptoms
of withdrawal every 4 to 6 hours for 24 hours
after initial dose. Range for daily dose is 15 to
30 mg in 24 hours. Repeat total first day dose
in a single dose or two divided doses
(stabilization dose) for 2 to 3 days, then
reduce dosage by 5 to 10 mg per day until
medication is completely withdrawn.
Methadone cannot be given for detoxification
from other opiates unless licensed by the
federal government or a medical comorbidity
is the condition of primary treatment.
Information from references 5, 9 and 10.
Naltrexone
Naltrexone (ReVia) is an opioid antagonist that acts at opiate receptors to
competitively inhibit effects of opiate agonists. It has no analgesic activity
of its own. Preliminary controlled double-blind studies suggest that
naltrexone is effective in decreasing the mean number of drinking days per
relapse and in reducing the subjective craving for alcohol. Study subjects
who relapsed tended to drink less alcohol and had shorter relapse periods
than control subjects. Naltrexone was considered to be an adjunctive
treatment, since all study subjects also were undergoing psychosocial
forms of treatment for alcoholism.15-17
While interest in developing these agents appears warranted, caution is
urged because of disappointment in the clinical efficacy of naltrexone in
previous studies of patients addicted to opiates (except those who are most
highly motivated).
Use of Psychosocial
Addiction Treatment to
Prevent Relapse
Medical management of alcohol and
drug withdrawal often is not sufficient
to produce sustained abstinence from
recurrent use. Therefore, other types
of addiction treatment are indicated to
prevent relapse to alcohol and drug
use following treatment of
withdrawal.18
Methadone itself is addicting
but because it decreases
intravenous drug use and HIV
infection, it may be useful in
those who cannot or will not
accept an abstinence-based
addiction treatment program.
Cost Benefits of Treatment
Historically, addiction treatment has not been integrated within the
mainstream of the health care system, even though such treatment is
effective and reduces health care costs. More accurate data on treatment
outcomes and costs are needed so that informed and rational decisions
about addiction treatment can be formulated by consumers, insurers,
physicians and policy makers. Fortunately, the results of several recent
health services research studies unequivocally demonstrate the cost
effectiveness of addiction treatment.19-22
Treatment Approaches and Effectiveness
The abstinence-based method is commonly used to treat alcohol/drug
addiction (95 percent of programs surveyed). This method utilizes
cognitive behavior techniques and referral to 12-step recovery programs,
such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA).23
One-year abstinence rates of 80 to 90 percent were achieved when patients
participated in weekly continuing care and/or AA meetings after discharge
from the treatment program (Table 7). Also, one-year abstinence rates
were associated with reduced rates of medical and psychiatric utilization18
(Table 8).
TABLE 7
One-Year Abstinence by Continuum of Care and Self-Help
Support
Inpatients (N=6,508)
Care criteria
Outpatients
(N=1,572)
Attending Abstinent Attending Abstinent
(%)
(%)
(%)
(%)
Months of continuing care
attending in one year
0
1 to 5
6 to 11
12
42
32
19
8
53
55
71
88
34
33
18
14
48
61
68
89
54
46
47
74
43
57
49
80
AA attendance
Non-attender
Regular attender
AA=Alcoholics Anonymous
Information from reference 23.
TABLE 8
Medical Care Utilization One Year Before and After Treatment
Inpatients (N=6,508)
Care criteria
Outpatients
(N=1,572)
Attending Abstinent Attending Abstinent
(%)
(%)
(%)
(%)
Hospitalizations
Medical
Psychiatric
Detoxification
Any admission
23
5
16
28
10
2
4
14
16
4
9
21
7
1
2
9
31
3
30
22
1
24
29
3
29
22
1
23
Emergency department use
Medical
Psychiatric
Any emergency
department use
Information from references 18 and 23.
Recovery in Alcoholics Anonymous
According to results of a 1992 survey conducted by AA, the following
recovery rates were achieved. (1) Of those members sober in AA less than
one year, 41 percent will attend AA another year. (2) Of those members
sober more than one year and less than five years, 83 percent will attend
AA another year. (3) Of those members sober five years or more, 91
percent will attend AA another year.23
Attendance in an abstinence-based treatment program such as AA can
increase recovery rates from 41 to 80 percent in patients with
alcoholism.18,23 For this reason, patients with alcoholism should be referred
to AA following withdrawal treatment and during maintenance therapy.
The Authors
NORMAN S. MILLER, M.D.,
is associate professor of psychiatry and neurology and chief of the division
of addiction programs at the University of Illinois School of Medicine,
Chicago. He received a medical degree from Howard University,
Washington, D.C., and completed a residency in psychiatry at Johns
Hopkins Hospital, Baltimore, and a residency in neurology at the
University of Minnesota, Minneapolis.
MARK S. GOLD, M.D.,
is professor of psychiatry at the University of Florida Brain Institute,
Gainesville. He received a medical degree from the University of Florida
College of Medicine, Gainesville, and served a residency in psychiatry at
Yale University, New Haven, Conn.
Address correspondence to Norman S. Miller, M.D., University of
Illinois at Chicago Department of Psychiatry (MC 913), 912 S.
Wood Street, Chicago, IL 60612-7327. Reprints are not available
from the authors.
REFERENCES
1. U.S. Department of Health and Human Services, Public Health Service,
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
National Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism. Epidemiology of alcohol use and alcohol-related consequences. In:
Alcohol and health. Eighth special report to the U.S. Congress from the
Secretary of Health and Human Services. September 1993:1-35.
Bennett JC, Plum F, eds. Cecil textbook of medicine. 20th ed. Philadelphia:
Saunders, 1996.
Adams RD, Victor M, Ropper AH. Principles of neurology. 6th ed. New York:
McGraw-Hill, Health Professions Division, 1997.
Miller NS, Gold MS, Smith DE, eds. Manual of therapeutics for addictions.
New York: Wiley-Liss, 1997.
American Society of Addiction Medicine. Principles of addiction medicine.
Washington, D.C.: The Society, 1994.
Miller NS, Gold MS. Abuse, addiction, tolerance, and dependence to
benzodiazepines in medical and nonmedical populations. Am J Drug Alcohol
Abuse 1991;17:27-37.
Rickels K, Schweizer E, Case WG, Greenblatt DJ. Long-term therapeutic use of
benzodiazepines. I. Effects of abrupt discontinuation. Arch Gen Psychiatry
1990;47:899-907 [Published erratum appears in Arch Gen Psychiatry
1991;48:51].
Schweizer E, Rickels K, Case WG, Greenblatt DJ. Long-term therapeutic use of
benzodiazepines. II. Effects of gradual taper. Arch Gen Psychiatry 1990;47:90815.
Gorelick DA. Overview of pharmacologic treatment approaches for alcohol and
other drug addiction. Intoxication, withdrawal, and relapse prevention. Psychiatr
Clin North Am 1993;16:141-56.
Gold MS. Pharmacological therapies of opiate addiction. In: Miller NS, Gold
MS, eds. Pharmacologic therapies for drug and alcohol addictions. New York:
Marcel Dekker, 1995.
Giannini AT. Phencyclidine. In: Miller NS, ed. Comprehensive handbook of
drug and alcohol addiction. New York: Dekker, 1991:383-94.
Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, et al.
Disulfiram treatment of alcoholism. A Veterans Administration cooperative
study. JAMA 1986;256:1449-55.
Banys P. The clinical use of disulfiram (Antabuse): a review. J Psychoactive
Drugs 1988;20:243-61.
Weddington WW. Methadone maintenance for opioid addiction. In: Miller NS,
Gold MS, eds. Pharmacological therapies for drug and alcohol addictions. New
York: Dekker, 1995:411-18.
Volpicelli JR, Alterman AI, Hayashida M, O'Brien CP. Naltrexone in the
treatment of alcohol dependence. Arch Gen Psychiatry 1992;49:876-80.
16. O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B.
17.
18.
19.
20.
21.
22.
23.
Naltrexone and coping skills therapy for alcohol dependence. A controlled
study. Arch Gen Psychiatry 1992;49:881-7.
O'Malley SS. Opioid antagonists in the treatment of alcohol dependence: clinical
efficacy and prevention of relapse. Alcohol Alcohol 1996;31(Suppl 1):77-82.
Miller NS. Treatment of the addictions: applications of outcome research for
clinical management. New York: Haworth, 1995.
Gerstein DR, Johnson RA, Harwood H, Fountain D, Suter N, Malloy K.
Evaluating recovery services: the California Drug and Alcohol Treatment
Assessment (CALDATA). Sacramento, Calif.: State of California Department of
Drug and Alcohol Programs, 1994.
Iglehart JK. The American health care system. Managed care. N Engl J Med
1992;327:742-7.
Holder HD, Blose JO. The reduction of health care costs associated with
alcoholism treatment: a 14-year longitudinal study. J Stud Alcohol 1992;53:
293-302.
Turnure C. Minnesota Consolidated Fund, annual cost offsets. Minnesota
Department of Human Services, 1993.
Chappel JN. Long-term recovery from alcoholism. Psychiatr Clin North Am
1993;16:177-87.
Copyright © 1998 by the American Academy of Family
Physicians.
This content is owned by the AAFP. A person viewing it
online may make one printout of the material and may use
that printout only for his or her personal, non-commercial
reference. This material may not otherwise be downloaded,
copied, printed, stored, transmitted or reproduced in any
medium, whether now known or later invented, except as
authorized in writing by the AAFP.