TREATMENT OF ALCOHOL ABUSE/DEPENDENT PATIENTS WITH PSYCHIATRIC COMORBIDITY
RELEASE DATE: February 25, 2002
PA NUMBER: PA-02-067
EXPIRATION DATE: February 20, 2005, unless reissued.
PARTICIPATING INSTITUTES AND CENTERS (ICs):
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is
seeking research grant applications on the treatment of alcohol
dependent/abuse patients with comorbid psychiatric disorder(s)
(includes Axis I and Axis II disorders as defined by the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]). The
purpose of this program announcement is to not only develop effective
interventions, but to also develop behavioral techniques to enhance the
engagement, retention, and adherence of patients with comorbidities to
treatment programs. Research on the specific assessment and treatment
needs of this population is in early stages, and thus well-designed
research projects are needed. In particular, effective pharmacological
and behavioral interventions tailored to the comorbid conditions need
to be discovered, developed, and evaluated. It is also important to
understand the effects of treating the concurrent disorders on
alcoholism treatment outcomes. The intervention strategy to address
both the alcohol dependence and the psychiatric condition might depend
on the type of comorbidity and the subtype of comorbid alcoholic
patient. All applications submitted in response to this program
announcement should be conducted in humans.
Alcohol dependent individuals have exceptionally high rates of co-
For example, in the U.S.
alcohol abuse and dependent patients are 20.1 times more likely to have
a diagnosis of antisocial personality disorder than are nonalcoholics
(Regier et al., 1990). Comparable odds ratios are 1.7 to 3.6 times for
major depression, 2.4 times for panic disorder, 1.4 times for phobia,
5.1 times for bipolar disorder, 3.3 times for schizophrenia, and 7.1
times for other drug addiction (Helzer and Pryzbeck, 1988; Regier et
al. 1990, Grant and Harford, 1995). Moreover, a significant number of
alcoholics, especially women, exhibit two or more comorbidities.
Interestingly, this population is more likely to seek alcoholism
treatment than non-comorbid alcoholics. In spite of comorbidity rates
being especially high among alcoholics in treatment, the prognosis for
treatment is often poor, particularly among patients with more severe
psychiatric illness. Furthermore, alcoholics with collateral
psychopathology appear less compliant with treatment and are more
likely to drop out of treatment, have a higher suicide rate, and
receive less support for sobriety from family and the work environment
(Cornelius et al., 1995; Woody, 1996; Drake and Mueser, 1996;
Greenfield et al., 1998).
Development of effective strategies to treat this population is at
early stages of research. The type of strategy may depend on the type
of psychiatric disorder and the severity of the psychiatric condition.
For example, McLellan et al. (1983) demonstrated that alcoholics with
low psychiatric severity improved with all tested treatment programs,
those with medium psychiatric severity demonstrated a variation of
outcomes to different treatment interventions, while those with high
psychiatric severity showed no improvement in any treatment.
Progress has recently been made in conducting state-of-the-art studies
of pharmacological and behavioral interventions in a number of comorbid
psychiatric disorders. For example, several NIAAA-supported trials
have been completed in depressed alcoholics. Results have been mixed.
Mason et al. (1996) demonstrated that while the tricyclic
antidepressant desipramine reduced symptoms of depression in alcoholic
patients with major depression, it had limited success in reducing
drinking. Similarly, McGrath et al. (1996) found that the tricyclic
antidepressant imipramine was effective in reducing depressive symptoms
in alcoholics with mild to moderate depression, but no differences in
alcohol intake between the imipramine and placebo groups were evident.
Effects of selective serotonin reuptake inhibitors (SSRIs) are less
clear. Cornelius and colleagues (1997) showed that fluoxetine
diminished both depression and drinking in severely depressed
alcoholics. In contrast, Pettinati et al. (2001), McGrath (1998), and
Moak et al. (2001) reported that the SRRI sertraline or fluoxetine was
no more effective than placebo in reducing the severity of depression
or drinking in a population of less severely depressed alcoholics.
Thus it appears that although antidepressants, in at least certain
conditions, can improve depression, and to at least a limited extent,
reduce drinking, their effects may vary and may also be a function of
subtype of depressed alcoholics. Investigations are currently underway
to determine if the pharmacological treatment of both disorders
(naltrexone for alcoholism and sertraline or fluoxetine for depression)
is more effective than monotherapy.
Few studies have been conducted to test the efficacy of behavioral
therapies in depressed alcoholics (Brown and Ramsey, 2000). Brown et
al. (1997) found that cognitive-behavioral therapy for depression was
effective not only in improving depression but also in decreasing
frequency of drinking in alcoholics with elevated depressive symptoms.
However, future studies on depressed alcoholics need to develop and
test behavioral therapies that address both depression and alcohol
disorders and also to determine their optimal integration with
for alcohol abuse/dependent patients with generalized anxiety disorder,
social anxiety disorder, posttraumatic stress disorder (PTSD), and
panic disorder. Buspirone, a partial 5-HT1A agonist, has been evaluated
in several trials using alcoholic patients with a collateral
generalized anxiety disorder. Tollefson et al. (1992) and Kranzler et
al. (1994) found it effective in reducing the symptoms of anxiety in
anxious alcoholics. Moreover, Kranzler and colleagues showed that
concurrent with improvement of anxiety, patients treated with buspirone
were more likely to stay in treatment and to delay return to heavy
drinking. On the other hand, Malcolm et al. (1992) failed to
demonstrate differences in improvement of anxiety or reduction in
drinking outcome in buspirone-treated versus placebo-treated
In alcoholic patients suffering from a comorbid social anxiety
disorder, Randall et al. (2001) found unexpectedly that a cognitive
behavior therapy specific for alcohol dependence was more effective in
reducing drinking than one designed to simultaneously address both
alcoholism and social anxiety. Further, the improvement in social
anxiety was equivalent for both therapies. A new trial has been
initiated to determine efficacy of paroxetine in individuals with a
dual-diagnosis of alcohol use disorder and social anxiety disorder.
Najavits et al. (1998) reported that a group cognitive behavioral
therapy designed for women suffering from both substance dependence and
PTSD was effective in reducing substance use and improving trauma-
related symptoms and family functioning in this population (59 percent
were dependent on alcohol). Trials are currently underway to evaluate
naltrexone in comorbid PTSD alcoholics and a cognitive behavioral
therapy for panic disorder in patients dually diagnosed with alcohol
dependence and panic disorder.
Finally, even less is known about the treatment of alcoholics with a
more severe mental illness. NIAAA is currently supporting a trial of
valproate in alcohol dependent patients with bipolar disorder and
clozapine in schizophrenic alcoholics. In a recent pilot study,
clozapine was found to be effective in reducing the frequency of
drinking in patients dually diagnosed with alcohol use disorder and
schizophrenia or schizoaffective disorder (Drake et al., 2000).
In summary, research to evaluate effective pharmacological and
behavioral treatments for patients diagnosed with alcohol use disorder
and psychiatric comorbidity is still in early stages. The purpose of
this program announcement is to stimulate additional quality research
to develop effective treatments to improve outcome and also to increase
engagement, retention, and adherence to a treatment program across a
wide population of alcohol abuse/dependent subjects with
A wide variety of research opportunities exist for advancing the
treatment of this understudied population. Research on topics such as
the following is urged.
o Development and evaluation of specialized pharmacological and
behavioral interventions for comorbid patients. This would include
development of effective treatment strategies for alcoholic patients
with multiple comorbidities (e.g., depression, anxiety disorders, and
illicit drug addiction). Appropriate combination and sequencing of
pharmacological and behavioral therapies need to be explored.
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