The American Journal on Addictions 12:S26^S40, 2003 Published by Brunner-Routledge

# 2003 American Academy of Addiction Psychiatry 1055-0496/03 $12.00 + .00

DOI: 10.1080/10550490390202398

Dual Diagnosis: Alcoholism

and Co-Morbid Psychiatric
Disorders
Henry R. Kranzler, M.D., Richard N. Rosenthal, M.D.

Although alcohol use disorders are commonly associated with co-morbid drug
use and psychiatric disorders, such co-morbidity is frequently underdiagnosed
and inadequately treated. This paper reviews the epidemiological, diagnostic,
and treatment literature on the co-morbidity of alcoholism, with a focus
on the most common co-morbid disorders: drug abuse, mood disorders, anxiety
disorders, and antisocial personality disorder. The paper goes on to describe a
number of promising approaches to the treatment of these common co-morbid
disorders in alcoholics. Despite the difficulties inherent in treating dual diag-
nosis patients, the clinician must recognize that it is possible to derive
valid diagnoses and deliver efficacious treatment to such patients.
(Am J Addict 2003;12[Suppl 1]:S26^S40)

C o-morbidity is defined as the presence

of any co-occurring condition in a
patient with an index disease.1 In this
paper, we will focus on psychiatric dis-
orders that are co-morbid with alcohol
abuse or dependence (ie, alcoholism). We
will focus the discussion on the four most
common co-morbid conditions: drug use
disorders, mood disorders (specifically,
bipolar and major depressive disorder),
anxiety disorders, and antisocial personality
disorder (ASPD). The reader is referred to
other sources for more comprehensive con-
sideration of these and other psychiatric
disorders that occur with alcohol and drug
use disorders.2^4
Co-morbidity has important clinical
implications for alcoholics, among whom
psychiatric symptoms increase the risk for
suicide.5 Concurrent alcohol dependence is
also associated with increased suicidality
among depressed patients.6 In addition, a
lifetime psychiatric diagnosis generally
predicts a poorer outcome during the years

Received August 15, 2002; accepted December 30, 2002.

From the Department of Psychiatry and the Alcohol Research Center, University of Connecticut School of
Medicine, Farmington, Conn. (Dr. Kranzler); and the Department of Psychiatry, Columbia University College
of Physicians and Surgeons, New York, NY, and the Department of Psychiatry, St. Luke’s-Roosevelt Hospital
Center, New York, NY (Dr. Rosenthal). Address correspondence to Dr. Kranzler, Professor of Psychiatry and
Associate Scientific Director, Alcohol Research Center, University of Connecticut School of Medicine, 263
Farmington Ave., Farmington, CT 06030^2103. E-mail: kranzler@psychiatry.uchc.edu.

S26

following treatment.7,8 Alcoholics with
ASPD have been shown to have an earlier
onset of alcoholism, more drug abuse,
lower rates of treatment retention, and a
poorer prognosis than alcoholics without
the disorder.7^10 Similarly, patients with
bipolar disorder and alcoholism have more
hospital admissions,11 a shorter period of
time before relapse,12 an earlier onset of the
mood disorder, more dysphoria, and a
poorer clinical course13 than bipolar
patients without alcoholism.
The paper begins with a review of the
epidemiology of alcoholism and common
co-morbid psychiatric disorders, including
estimates derived both from the com-
munity and clinical samples. This is
followed by a discussion of the diagnostic
and therapeutic issues that are unique to
the management of co-morbid disorders in
alcoholics.
INCIDENCE AND PREVALENCE OF
ALCOHOLISM AND CO-MORBID
DISORDERS
Community Studies
Two large-scale community studies
conducted over the past twenty years pro-
vide estimates of the lifetime and past year
prevalence of alcoholism and a variety of
co-morbid psychiatric disorders. The Epi-
demiological Catchment Area Survey
(ECA), which used DSM-III criteria,
included more than 18,000 household
respondents and more than 2,000 insti-
tutional respondents from five communi-
ties in the U.S.14 The National
Comorbidity Study (NCS), which used
DSM-III-R criteria, was a representative
household survey of more than 8,000
persons.15
The ECA estimated that 13.5% of the
U.S. population had experienced an alcohol
disorder at some time in his or her life,14
with the one-year prevalence estimate
being 7.3%.16 More than one-third of
THE AMERICAN JOURNAL ON ADDICTIONS
Kranzler & Rosenthal
respondents with a lifetime alcohol use dis-
order received at least one other psychiatric
diagnosis, a rate approximately double that
for community respondents with no life-
time alcohol disorder.14 Similarly, ECA
data demonstrate that a history of a mental
disorder nearly triples (ie, odds ratio [OR]
of 2.9) the likelihood that an individual
will have a lifetime alcohol disorder.14
The NCS estimated that the lifetime
prevalence of alcohol abuse or dependence
for adults 18 to 54 years was 9.4% and
14.1%, respectively.15 The prevalence of
alcohol abuse and dependence during the
twelve months preceding the interview was
2.5% and 4.4%, respectively.15 A co-
morbid psychiatric disorder is more
common among women with an alcohol
use disorder and more likely to occur with
alcohol dependence than alcohol abuse.
Among women, 86.0% of those with
alcohol dependence and 72.4% of those
with alcohol abuse had a co-morbid life-
time psychiatric or drug use disorder.15
Among men, the comparable figures for
alcohol dependence and abuse were 78.3%
and 56.8%, respectively.15
Women diagnosed with an alcohol dis-
order appear to be at greater risk for a
co-morbid psychiatric disorder, with the
relative risks for different types of disorder
also varying by gender.15,17 Among
women with a history of alcohol abuse or
dependence, anxiety and mood disorders
are the most common co-morbid disorders;
among men, drug disorders and antisocial
personality disorder account for the largest
proportion of co-morbid cases.
Drug Use Disorders. In the ECA, 21.5% of
alcoholics also had a lifetime drug use dis-
order (OR ¼ 7.1);14 similarly, among indi-
viduals with a drug use disorder, 47.3%
also had an alcohol disorder. The associ-
ation was strongest for individuals with
cocaine abuse/dependence, among whom
84.8% also had an alcohol use disorder
(OR ¼ 36.3). Other drug use diagnoses
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Alcohol Abuse and Alcoholism
with an odds ratio in excess of 10.0
included barbiturates, opiates, amphet-
amines, and hallucinogens.13
In the NCS, the prevalence of a drug
use disorder was also high among both
male and female alcoholics. In that study,
more than 40% of individuals with an
alcohol disorder had co-morbid drug
abuse or dependence.15 Although nicotine
dependence is a common co-morbid
disorder among alcoholics, recent national
survey data on the co-occurrence of
these disorders have not yet been
published.
Mood Disorders. In the ECA, mood dis-
orders were present in 13.4% of alcoholics
(OR ¼ 1.9),14 and 21.8% of individuals
with a mood disorder also had an alcohol
use disorder. This co-morbidity was par-
ticularly high among individuals with
bipolar disorder, 43.6% of whom had a life-
time alcoholism diagnosis (OR ¼ 5.1).
Other mood disorders, though generally
more common than bipolar disorder,
show substantially lower odds ratios with
alcoholism. Specifically, unipolar depres-
sive disorder, which is present in 16.5%
of alcoholics, has an odds ratio of only
1.3. Important gender differences in the
relations between diagnoses were evident.
Among alcoholics, women were about
four times as likely as men to receive a
mood disorder diagnosis.17 Similarly,
major depressive disorder was the
antecedent diagnosis in the majority of
cases of co-morbidity for women while
among men alcoholism was more likely
to be the antecedent diagnosis.15,17
Anxiety Disorders. In the ECA, 19.4% of
alcoholics had a co-morbid anxiety disorder.
This yielded an OR of only 1.5,14 which is
surprising given the high prevalence of
anxiety disorders in the general population.
Among individuals with an anxiety disorder,
17.9% had a co-morbid alcohol use disorder.
Of the anxiety disorders, panic disorder had
S28 VOLUME 12
SUPPLEMENT 1
2003
the strongest association with alcoholism:
28.7% of individuals with that disorder
also have an alcohol use disorder (OR ¼
2.6). Obsessive-compulsive disorder
(OR ¼ 2.1) is intermediate between panic
disorder and phobias (OR ¼ 1.4).14
Among alcoholics, women were more
than three times as likely as men to have
panic disorder and more than twice as
likely to have a phobia.17 Evidence suggests
that the onset of social phobia occurs prior to
the onset of alcohol use disorder and that
self-medication may play a role in the
co-occurrence of the two disorders.18 A his-
tory of posttraumatic stress disorder
(PTSD) has been found among 10.3% of
men and 26.2% of women with alcohol
dependence, and alcohol use disorders
have the highest prevalence of any
co-morbid mental disorder among men
with PTSD.15 In the NCS study, the onset
of an anxiety disorder appeared to precede
the onset of an alcohol use disorder for
women more commonly than for men.15
Antisocial Personality Disorder. In the
ECA, ASPD was present in 14.3% of
alcoholics for an OR of 21.0.14 Conversely,
73.6% of ECA respondents with ASPD
also met criteria for alcoholism. It should
be noted that there is substantial overlap
in diagnostic criteria for these disorders
(eg, antisocial behavior that is manifest
as a consequence of intoxication).
Clinical Studies
Although community prevalence rates
provide evidence that psychiatric disorders
occur commonly among alcoholics in the
community, the rates in treatment-seeking
populations are even higher. This may
reflect greater treatment-seeking behavior
among patients with co-morbidity, which
has come to be known as ‘‘Berkson’s
Bias.’’19 Despite the high community
prevalence of alcoholism, it has been esti-
mated that only 19% of patients with

12-month alcohol dependence are in any
outpatient treatment in a year.20 However,
psychiatric co-morbidity tends to drive up
service utilization. For example, co-
occurring 12-month anxiety or mood dis-
orders increased the rate of any outpatient
treatment of current alcoholics to 41% in
one year.20
Consistent with the patterns observed
in the general population, the most
common co-morbid disorders in clinical
samples are drug dependence, major
depressive disorder, ASPD, and anxiety
disorders.21^24 However, the prevalence
of co-morbid disorders in the clinical
setting varies with a number of factors,
including characteristics of the sample
(eg, gender), method of assessment, and
the time elapsed between assessment and
cessation of heavy drinking.25^32 Given
the overlap in the diagnostic criteria for
alcohol dependence and ASPD and the
effects of chronic heavy drinking on
mood and anxiety symptoms, care must
be taken to differentiate transient,
alcohol-related symptoms from those that
persist beyond the period of heavy
alcohol consumption. This issue is con-
sidered in greater detail in the following
section on assessment.
In a study of the lifetime prevalence of
DSM-III disorders among 565 male
inpatient alcoholic veterans, 63% had a
psychiatric diagnosis in addition to alcohol
dependence.21 The most common co-
morbid diagnosis in this sample was
depression (42% of all patients), followed
by mania (20%) and ASPD (20%).
Co-morbid drug abuse was present in 12%
of patients, with panic attacks, phobic dis-
order, and obsessive-compulsive disorder
each diagnosed in approximately 10% of
patients. With the exception of depression
and obsessive-compulsive disorder, the
onset of co-morbid disorders occurred
prior to the onset of alcoholism.
In a group of 321 individuals with
an alcohol use disorder recruited from
THE AMERICAN JOURNAL ON ADDICTIONS
Kranzler & Rosenthal
three different inpatient settings, 75%
of men and 80% of women received one
or more lifetime diagnoses in addition
to alcohol abuse/dependence.22 Overall,
drug abuse was the most prevalent life-
time diagnosis (45%), followed by ASPD
(41%), major depressive disorder (38%),
phobia (27%), obsessive-compulsive dis-
order (12%), panic disorder (10%), and
mania (4%). The prevalence of these dis-
orders varied by gender, with ASPD
being the most common among men
(49%) and depression the most common
among women (52%). The onset of most
co-morbid disorders in women preceded
the onset of alcohol abuse, while among
men most co-morbid disorders followed
the onset of alcohol abuse.
In a sample of 501 patients seeking
substance abuse treatment,23 370 patients
were diagnosed with an alcohol use dis-
order. Of this number, 25% had a
co-morbid drug diagnosis. Patients with
both alcohol and drug use disorders had a
higher prevalence of other lifetime psychi-
atric diagnoses (95%) than those with only
an alcohol diagnosis (78%). The most
common disorder among patients with
combined alcohol and drug use disorders
was ASPD (79%), followed by major
depression (36%), phobias (36%),
obsessive-compulsive disorder (18%), panic
disorder (17%), and mania (3%). A similar
distribution of co-morbid diagnoses was
obtained in patients without a co-morbid
drug diagnosis, although in each case, the
prevalence was lower. Alcoholism most
commonly occurred after the onset of
ASPD, phobias, and panic disorder.
Onset of the other co-morbid disorders
relative to an alcohol diagnosis was more
variable.
Generally speaking, clinical studies
that have examined a variety of co-morbid
disorders in alcoholics have not included
the diagnosis of nicotine dependence.
However, a review of eleven studies
revealed that 83% of alcoholics were
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Alcohol Abuse and Alcoholism
current smokers, nearly triple the rate of
smoking in the general population.33
Alcoholics were also more likely to smoke
heavily.33 Alcohol dependence, nicotine
dependence, and other psychiatric dis-
orders, such as major depression, have also
been shown to co-vary.34
In summary, both community and
clinical studies underscore the importance
of ASPD and drug abuse/dependence as
co-morbid diagnoses in alcoholics. The
odds ratios obtained for these disorders in
community studies suggest that these as-
sociations may be elevated not only as a
function of greater treatment-seeking
behavior in co-morbid individuals but also
because alcoholism may share with drug
use and antisocial personality disorders
some etiological and developmental
factors. In contrast, although mood and
anxiety disorders are highly prevalent in
clinical samples, their association with
alcoholism appears largely due to chance,
as these disorders are also highly prevalent
in the general population.
TABLE 1. Possible Interactions Between Alcoholism and Co-morbid Psychiatric
Symptoms
Interaction
Axis I or Axis II disorders as risk
factors for alcoholism
Psychiatric symptoms develop in the
course of a chronic intoxication
and follow the course of
alcoholism
Psychiatric disorder that occurs as a
consequence of substance use but
persists after cessation of
substance use
Substance abuse and psychiatric
symptomatology meaningfully
linked over time
No relationship between substance
abuse and psychiatric
symptomatology
Adapted From references 3 and 4.
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DIAGNOSTIC ISSUES IN ALCOHOLICS
WITH CO-MORBID DISORDERS
Given the high rate of co-morbidity of
alcoholism and psychiatric disorders, care-
ful psychiatric assessment should be con-
ducted routinely in patients being seen for
alcohol treatment, and alcohol use and
associated problems should routinely be
evaluated in patients being seen primarily
for other psychiatric conditions. In
alcoholics, one can see intentional or inad-
vertent distortion of personal history, so
the clinician should obtain a history from
significant others whenever possible.
However, once the diagnosis is made of a
co-occurring psychiatric and alcohol use
disorder, the clinician is faced with the task
of understanding the interactions that may
exist between the conditions. Table 1 pro-
vides an overview of the possible relation-
ships between alcoholism and co-morbid
psychiatric symptoms.
Although discerning the relationship
between the disorders can be challenging,
Example
The individual with social anxiety
who ‘‘prepares’’ for a party by
drinking to relieve anxiety
The individual whose heavy
drinking causes sleep impairment
and other mood symptoms that
remit gradually upon the cessation
of drinking
Panic attacks triggered by alcohol
withdrawal that persist long after
withdrawal has abated
Bipolar II patient whose heavy
drinking is limited to periods of
hypomania
The depressed alcoholic whose
symptoms do not remit with pro-
longed abstinence from alcohol
 Kranzler & Rosenthal

TABLE 2. Questions That May Help to Clarify the Relationship Between Alcohol Use and Psychiatric
Symptoms
1) When did psychiatric symptoms ¢rst occur (or, if an exacerbation, when did they recur)?
2) When did symptoms of alcohol use disorder ¢rst occur (or, if a relapse, when did they recur)?
3) What subjective e¡ects does the use of alcohol have on psychiatric symptoms (eg, relief, exacerbation)?
4) What e¡ects does cessation of drinking have on mental symptoms?
5) What e¡ects does the amelioration of psychiatric symptoms have on patterns of alcohol use?
Adapted From reference 3.

by considering phenomenology, time depressive symptoms declined substantially

course, and etiology, the clinician will be in
the best position to prescribe an efficacious
treatment. Diagnoses may require serial
treatment contacts to clarify the relation-
ship of the onset and persistence of mental
symptoms to the intervals over which
heavy drinking takes place. Other issues
that require consideration are shown in
Table 2.
In the differential diagnosis of
co-morbid disorders, it is important to
determine how long the symptoms have
persisted and whether they preceded the
onset of substance abuse (though
frequently, the chronology of onset of the
disorders cannot be established during the
initial evaluation). Establishing the chron-
ology of onset of diagnoses may be helpful
in planning treatment, as the clinical pic-
ture tends to run the course of the primary
disorder.10 For example, patients with pri-
mary alcoholism have significantly fewer
episodes of affective disorder compared to
bipolar patients with secondary
alcoholism.25^26
The way in which symptoms change
with the cessation of drinking may also be
an important clue as to the etiology of
those symptoms. The evaluation of
depressive symptoms, which are very
common in alcoholics, provides an example
of this approach, as frequently there is a
decrease in depressive symptoms once
sobriety is established.27^29 Dorus and
colleagues27 found that, whereas 67% of
patients were classified as depressed on
admission using a symptom inventory, any
by day 4, with only 50% of patients having
enough symptoms to be considered
depressed. Furthermore, using a diagnostic
interview on day 24 of the hospital stay,
only 16% of patients met criteria for major
depression.
Depressed alcoholics present a complex
picture: a chronic low-grade mood disorder
that may predispose the patient to drink,
with exacerbation of depressive symptoms
by chronic heavy drinking. The patient
may present with a complaint of severe
mood disturbance, and only with appropri-
ate history taking does the role of heavy
drinking in symptom exacerbation emerge.
Similar findings have been seen in
relation to anxiety symptoms. Although
such symptoms are prominent during
alcohol withdrawal,30 as with depressive
symptoms, alcoholics’ anxiety level declines
as a function of the duration of abstinence
from alcohol.31,32
TREATMENT OF ALCOHOLISM AND
CO-MORBID DISORDERS
Initial treatment for alcohol depen-
dence consists primarily of detoxification
and psychosocial strategies to maintain
abstinence. The presence of a co-morbid
psychiatric disorder can substantially com-
plicate these efforts. For example, depen-
dence on drugs other than alcohol may
augment or mask alcohol withdrawal
symptoms. Mood symptoms (eg, decreased
energy and interest) can interfere with an
individual’s active participation in

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Alcohol Abuse and Alcoholism
treatment, and anxiety symptoms (eg,
social anxiety) may make it difficult to
attend AA meetings or to participate in
group therapy. Alcoholics with ASPD may
show manipulative or aggressive behaviors
that can interfere with their recovery and
that of other patients.
Despite a need for evidence-based
approaches to the treatment of alcoholics
with co-morbid disorders, the treatment
literature relevant to this population is
dominated by antidepressant trials for
depressed alcoholics. Although cognitive
behavioral therapy (CBT) has been shown
to be useful in treating patients with
alcohol dependence as well as those with
depressive and anxiety disorders, there has
been limited research on the utility of
integrated psychotherapeutic interventions
that address the needs of alcoholics with
co-morbid disorders. Given the paucity of
empirical research on specific interventions
for co-morbid disorders, most of what is
recommended in this section has an
experiential/rational basis and has yet to be
validated scientifically. Nonetheless, it
should be clear that no one approach will
suffice in the treatment of co-morbid
disorders.
For acutely ill patients, the appropriate
intensity of services will depend upon the
presenting severity of illness as well as
factors such as medical risk or the need for
protection from self- or other-directed
harm. Two traditional approaches to
treating dually diagnosed patients are serial
treatment (where either the mental disorder
or alcohol use disorder is addressed first)
and parallel treatment (where both dis-
orders are addressed concurrently, but
typically without formal interaction of the
clinicians or programs involved).
Models of integrated treatment aim to
synthesize traditional mental health and
addiction counseling, with the result being
treatment that appears seamless to patients
with respect to its general approach, philo-
sophical underpinnings, and psycho-
S32 VOLUME 12
SUPPLEMENT 1
2003
educational content.35^37 Such coordinated
psychiatric and alcohol rehabilitation ser-
vices may lead to better outcomes.38
Treatment Modalities
Psychotherapeutic Approaches. Many clini-
cians integrate elements of supportive
therapy, cognitive-behavioral therapy
(CBT), and motivational techniques in
their psychotherapeutic approach to the
dual diagnosis patient. Efforts to enhance
motivation for recovery can be initiated
during the first contact with the patient
(eg, during detoxification) and can be
accomplished by providing nonjudgmental
feedback to the patient on the specific
medical, social, interpersonal, or psychiatric
effects of his or her drinking. Relapse pre-
vention (ie, CBT) strategies can be added
after detoxification is complete, assuming
that the patient is adequately motivated
for such treatment. CBT focuses on the
acquisition of skills that can be used to
manage high-risk drinking situations or
reduce psychiatric symptoms. Depressed
or anxious mood states are often a cue
for drinking, so teaching patients to
avoid high-risk drinking situations can
readily be paired with teaching them to
manage such moods more effectively.
In summary, psychotherapeutic
interventions aimed at alcoholics with
co-morbid psychiatric disorders should
address both the alcohol dependence and
the co-morbid psychiatric disorder.
Specifically, an effort should be made to
assess and enhance motivation, engage and
retain patients in treatment, educate the
patient on the relationship between alcohol
use and psychiatric symptoms, and teach
him or her skills to manage symptoms.
Pharmacological Treatment Approaches. Since
many psychiatric symptoms subside with
abstinence, the use of medications to allevi-
ate such symptoms should generally be
 Kranzler & Rosenthal

postponed until at least one or two weeks
of abstinence have been achieved. At
least three weeks of abstinence from alcohol
may be necessary to identify patients whose
symptoms are unlikely to subside
spontaneously.29 However, under certain
clinical circumstances (eg, severe symptoms
and a clear history of a primary psychiatric
disorder that responded to medication),
more immediate action may be required.
In other cases, the assessment of symptoms
at regular intervals throughout treatment
will help to determine whether medications
are indicated. As with the pharmacotherapy
of alcohol dependence, the efficacy of
medication treatment of co-morbid dis-
orders is enhanced by concomitant
psychosocial interventions, including
those that increase medication com-
pliance.39 Although there is inadequate evi-
dence to permit a differential therapeutic
approach, there are some common-sense
principles that can be applied to the use
of medications in dually diagnosed patients,
as shown in Table 3.
Self-help Approaches. Although alcoholics
with co-morbid disorders may find AA
useful, they often require extra encourage-
ment to initiate and continue attendance
at fellowship meetings. Dual-diagnosis
patients may find it difficult to relate to
other AA members whose lives may
improve more rapidly than theirs as a
consequence of abstinence from alcohol.
Although not a formal position of
Alcoholics Anonymous, some members
hold the view that recovery should be
medication free and may discourage
patients from taking psychotropic
medications prescribed for a comorbid dis-
order. Patient education, an important
aspect of treatment, should include a dis-
cussion of how medications, psychiatric
symptoms, and drinking may interact
with one another. The physician should
discuss with the patient the potential for
criticism to be leveled against the use of
medication. Strategies should be considered
that allow the patient to derive the benefits
of AA attendance without having it disrupt
the treatment of a co-existing disorder.
Treatments for Specific Co-morbidities
Co-morbid Alcohol and Drug Use Dis-
orders. There is considerable overlap in
the psychosocial treatment of alcohol and
drug use disorders. Self-help groups that
deal with patients who abuse both classes
of substance promote abstinence from
both, on the theory that the use of
either alcohol or drugs increases the risk
for relapse to both. A systematic analysis
of the effects of treatment interventions
on both alcohol and drug use, however,
is limited.
A study of the addition of contin-
gency management (CM) to an 8-week
partial hospital program illustrates the
potential utility of this approach to the
treatment of co-morbid alcohol and drug
use disorders.40 In a sample of
alcohol-dependent patients, more than
half of whom had a history of cocaine
and/or opioid dependence, CM was sig-
nificantly better than standard treatment

TABLE 3. Basic Principles of Pharmacotherapy for Dually Diagnosed Patients

1) Treat alcohol-induced disorders acutely only for reasons of safety or medical management.
2) Try to avoid medications with a high abuse liability.
3) Be parsimonious in your choice of medications and their dosage, without undertreating.
4) Focus on treatment of syndromes that are less risky to treat than symptoms.
5) Provide psychoeducation and support for compliance with the prescribed regimen.
Adapted from reference 3.

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Alcohol Abuse and Alcoholism
with respect to both treatment
completion and abstinence from alcohol.
CM also significantly reduced the
number of urine tests that were positive
for drugs of abuse.
With respect to pharmacological
treatments, a pilot study by Carroll et al.41
showed an advantage for disulfiram over
naltrexone among patients with co-morbid
alcohol and cocaine dependence. Consistent
with these findings, Hersh et al.42 found no
advantage for naltrexone over placebo
among subjects with both alcohol and
cocaine use disorders. Carroll et al.43 exam-
ined CBT and Twelve Step facilitation
(TSF) alone and in combination with dis-
ulfiram for the treatment of co-morbid
alcohol and cocaine dependence. Although
the study did not include a placebo control,
the addition of disulfiram was associated
with significantly better retention in treat-
ment and a longer duration of abstinence
from alcohol and cocaine. The two active
psychotherapies (CBT and TSF) were also
associated with reduced cocaine use com-
pared with clinical management. The
results of this study underscore the poten-
tial clinical advantage of combining
psychotherapy with medication to treat
co-morbid alcohol and cocaine
dependence.
Liebson et al.44 evaluated the effects of
contingent administration of disulfiram
among alcohol-dependent opiate addicts
who were threatened with discharge from
methadone treatment due to their
alcoholism. Patients were randomly
assigned to a contingent disulfiram con-
dition, in which methadone was dispensed
only if the subject ingested disulfiram, or
non-contingent methadone, in which
subjects were encouraged but not required
to take disulfiram to receive their
methadone. Patients in the CM group had
significantly fewer drinking days than the
non-contingent disulfiram group. The CM
group also had less illicit drug use, lower
arrest rates, and higher employment rates
S34 VOLUME 12
SUPPLEMENT 1
2003
than the non-contingent group. These
findings also underscore the potential value
of combining a specific psychotherapeutic
approach with pharmacotherapy to treat
co-morbid alcohol and drug use disorders.
With respect to co-morbid alcohol and
nicotine dependence, a variety of treatment
approaches are available.45 Included among
these are nicotine replacement (gum, patch,
nasal spray, inhaler, and lozenge), largely
available over-the-counter, and bupropion;
all of these appear to be equal in efficacy,
with an approximate doubling of the quit
rate over placebo. Concomitant behavioral
or supportive therapy can further increase
this rate of response. The literature does
not yet provide a clear indication as to
which approach is optimal for smokers
who are alcohol dependent.
Co-Morbid Alcohol Dependence and Mood
Disorders. Although early studies of tri-
cyclic antidepressants (TCAs) showed
them to be no better than placebo for the
treatment of depression in alcoholics, this
lack of efficacy may have been due to the
methodological shortcomings of these
trials.46 Placebo-controlled trials of
imipramine47,48 and desipramine,49 which
take these methodological considerations
into account, suggest that TCAs reduce
depressive symptoms in depressed
alcoholics. However, SSRIs and other,
newer antidepressants have a much better
safety profile than TCAs. A placebo-
controlled study by Cornelius et al.50 demon-
strated the efficacy of fluoxetine in reducing
not only mood symptoms in depressed
alcoholics but also the frequency of drinking
and of heavy drinking. However, fluoxetine
should probably not be used to maintain
abstinence or reduce drinking in earlier-
onset (ie, high-risk/severity or Type B)
alcoholics, as it may result in poorer
drinking-related outcomes compared to pla-
cebo treatment.51 A study by Roy52 showed
that sertraline also decreases depressive
symptoms in depressed alcoholics; however,

in a subsequent study, Pettinati et al.53 found
that sertraline was superior to placebo only in
later-onset (ie, low-risk/severity or Type A)
alcoholics. A secondary analysis of those
data yielded the counter-intuitive finding
that the active medication was superior to
placebo only among patients with no lifetime
history or family history of major
depression.54 More recently, nefazodone
was found to decrease depressive symptoms
in depressed alcoholics.55
The psychotherapeutic treatment of
co-morbid alcohol and depressive disorders
has received little research attention. One
randomized trial of alcoholics with high
levels of depression being treated in a
partial hospital program56 showed that
cognitive behavioral therapy of depression
produced significantly greater reductions
in depression and anxiety than relaxation
control treatment. At six-month follow-up,
patients in the experimental group had sig-
nificantly reduced drinking measures and
greater AA attendance.
To date, there are few published, con-
trolled studies of psychotherapy or
pharmacotherapy for bipolar disorder in
alcoholics. Although both lithium and
valproate have demonstrated efficacy in the
treatment of mania, limited evidence
suggests that substance abusers tend to have
subtypes of bipolar disorder (ie, mixed and
rapid cycling) that are less responsive
to lithium.12, 57 This possibility, coupled
with the potential toxicity of lithium in
overdose, has led clinicians increasingly to
prescribe anticonvulsants for the treatment
of co-morbid bipolar disorder in alcoholics.
Weiss et al. have developed an integrated
cognitive behavioral group psychotherapy
for co-morbid bipolar disorder and sub-
stance use disorder that focuses upon
relapse prevention for both disorders.58
Results of a pilot study demonstrated sig-
nificantly improved ASI drug composite
scores and months of abstinence in patients
who received the integrated group
therapy.59
THE AMERICAN JOURNAL ON ADDICTIONS
Kranzler & Rosenthal
Co-Morbid Alcohol Dependence and Anxiety
Disorders. Benzodiazepines, sometimes
used to treat anxiety in alcoholics, are
themselves subject to abuse and the poten-
tial for additive depressant effects with
alcohol. Therefore, buspirone, a non-
benzodiazepine anxiolytic, has been studied
in this patient group. A double blind,
placebo-controlled trial found significantly
greater retention in treatment and greater
decreases in alcohol craving, anxiety,
and depression in buspirone-treated
alcoholics.60 The groups showed compar-
able reductions in drinking. Similarly,
Tollefson and colleagues61 found that
buspirone-treated subjects were less likely
to discontinue treatment prematurely and
had greater reductions in anxiety than
placebo-treated subjects. An advantage
on a global measure of drinking was
also observed for the buspirone group,
although quantitative measures of alcohol
consumption were not reported in this
study, confirming previous studies.
Kranzler et al.62 found that buspirone
was superior to placebo in terms of
retaining anxious alcoholics in treatment.
Regardless of whether a specific anxiety dis-
order was present, buspirone treatment
reduced anxiety among subjects with the
highest anxiety symptom scores. The
active drug also delayed relapse to heavy
drinking. In contrast, a placebo-controlled
trial of alcoholic veterans showed no differ-
ence between buspirone and placebo on
measures of anxiety or alcohol con-
sumption,63 though in this study, the
medication was not administered in the con-
text of a psychosocial treatment program. In
summary,when combined with appropriate
psychosocial treatment, buspirone appears
useful in the treatment of alcoholics with per-
sistent anxiety. Furthermore, it may be
necessary to prescribe buspirone at the
highest recommended dosage (60 mg/day)
to obtain a good treatment response.
Despite evidence that a variety of
antidepressants are efficacious in the
S35
Alcohol Abuse and Alcoholism
treatment of panic disorder and social
phobia, there are no published, controlled
trials of the pharmacological treatment of
these disorders in alcoholics. Although the
efficacy of the SSRIs has not been
evaluated in alcoholics with these anxiety
disorders, these agents are the safest.
Further, with PTSD, SSRIs are the most
appropriate first-line medication, and
recent pilot evidence suggests that they
may be beneficial in co-morbid alcohol
dependence.64,65
With respect to psychotherapeutic
interventions, both serial and concurrent
models have been applied in the treatment
of alcoholics with PTSD, generating
controversy about the proper sequencing
of treatment. Clinicians advocating for con-
current approaches support reducing
PTSD symptoms and dysphoria by
addressing traumatic events earlier in treat-
ment in order to reduce the risk of relapse
to substance use.66,67 Although exposure
therapy for six months is considered appro-
priate therapy in PTSD,64 serial treatment
proponents have taken the position that
stable sobriety must be achieved before the
PTSD symptomatology is addressed in
alcoholics.68^70 In addition, current
research has not differentiated the treat-
ment sequencing between those with
PTSD who later developed alcoholism and
alcoholics who were traumatized and devel-
oped PTSD. Clearly, psychotherapeutic
interventions that focus on developing
coping skills and the direct reduction of
anxiety are first line interventions in PTSD
patients with co-morbid alcoholism.
There is limited research on
psychotherapeutic interventions for
alcoholics with other anxiety disorders.
One of the few studies to address this
issue showed that among anxious
alcoholics, those receiving anxiety manage-
ment and relaxation training experienced
greater decreases in anxiety symptoms
than a health education group.71 However,
there was no differential treatment effect
S36 VOLUME 12
SUPPLEMENT 1
2003
on drinking outcomes, either during treat-
ment or during a three-month follow-up
period.
Co-morbid Alcoholism and Antisocial Person-
ality Disorder. Although the role of
medications in treating ASPD patients
has been limited, certain medications may
improve symptoms associated with
ASPD, such as aggression and impulsivity.
For instance, a three-month course of
lithium was found to be efficacious in man-
aging aggression in prison inmates but
have no effect on other antisocial behaviors
in this population.72 In addition, there is
some evidence that fluoxetine helps per-
sonality-disorder patients with prominent
histories of impulsive, aggressive
behavior.73 However, it must be empha-
sized that the decision to prescribe
medications for these patients must be con-
sidered carefully. This includes identifying
target symptoms that may benefit from
medications, considering the potential
risks and benefits of a specific medication
and avoiding the use of medications with
abuse liability.
Despite substantial evidence of a
poorer prognosis among alcoholics with
ASPD,7,8 some studies have shown no dif-
ference in treatment response among
alcohol- and cocaine-dependent patients
based on the presence of co-morbid
ASPD.74 Similarly, in another study,
employed ASPD alcohol abusers
responded as well to abstinence-focused
CBT as did a heterogeneous group of
non-ASPD alcohol abusers.75 Contingency
contracting with explicit rules of conduct,
if negotiated at the outset of treatment, has
also been used in an effort to reduce disrup-
tive behaviors.
How to identify in advance those
ASPD alcoholics who can benefit from
treatment is an important question. The
ability to experience distress (eg, anxiety or
depression) may predict a positive
treatment response in ASPD alcoholics.76

Clinical features that contraindicate
psychotherapy in patients with ASPD
include a history of violent behavior that
results in serious injury or death, the
absence of remorse or rationalization of
antisocial behavior, the inability to develop
emotional attachments, and the elicitation
of intense fear in the skilled clinician by the
patient’s predatory behavior.77 Alcoholic
patients with moderate to severe ASPD
may require such highly structured pro-
gramming that treatment may not be poss-
ible in a regular outpatient setting and
under some circumstances, it may be
necessary to refer the patient to a long-term
residential treatment facility.
In the area of personality disorders,
dialectical behavior therapy (DBT) has
shown efficacy in the treatment of
borderline personality disorder (BPD),
which is characterized by instability of
mood, problematic interpersonal relations,
impulsivity, and self-destructive beha-
viors.78 In a randomized clinical trial,
Linehan et al. demonstrated better treat-
ment retention and reductions in substance
abuse in drug-dependent women with
BPD who are treated with DBT instead of
a more typical course of treatment.79 The
overlap of symptoms (eg, impulsive
aggression) among ASPD, BPD, and
alcohol dependence suggests that DBT
might profitably be adapted to address
some of the problematic behaviors of
heavy drinkers with ASPD.
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