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)
 (http://www.niaaa.nih.gov)
 
THIS PA CONTAINS THE FOLLOWING INFORMATION

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
o References

PURPOSE
 
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.

RESEARCH OBJECTIVES

Background

Alcohol dependent individuals have exceptionally high rates of co-
occurring psychiatric disorders (Regier et al., 1990; Grant and 
Harford, 1995; Kessler et al., 1996).   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 
pharmacological agents.

Research has just begun to identify and evaluate effective treatments 
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 
anxious alcoholics.

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 
psychiatric disorder(s).

Specific Areas of Interest

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.
 
o Identification of patient characteristics associated with concurrent 
disorders.  These include diagnostic status, biological status, 
phenotype, and developmental stage. Treatment strategies particularly 
suited to varying types of comorbid alcoholics need to be developed 
and tested.

o Determination of the effects of concurrent disorders on alcoholism 
treatment outcomes.  Does the treatment of either alcoholism or the 
concurrent psychiatric disorder improve outcome for the other disorder?

o Design of effective treatments for comorbidity in special populations 
including minorities, the elderly, adolescents, women, especially those 
who are pregnant, individuals with fetal alcohol syndrome, those in the 
criminal justice system, and individuals who are HIV positive or at 
high risk of becoming HIV positive.  It may be helpful to identify 
social and cultural factors that mediate and moderate motivation for 
treatment, adherence to treatment, and treatment outcomes. 

o Determination of the biological and behavioral overlaps of alcoholism 
and the comorbid condition. For example, do these conditions share 
similar neuronal circuit pathways?  Do they interact in a way that 
causes an increase in severity of one or both conditions?  This 
information may be helpful in the development of more effective 
treatment interventions.  

o Development of techniques for the engagement, retention, and 
adherence of comorbid patients in treatment.  Promising behavioral 
techniques include motivational interviewing and contingency 
management.  However, such techniques might have to be tailored to the 
type of comorbidity.  

o Development and evaluation of assessment and outcome instruments that 
measure the dimensions and characteristics of the psychopathology condition. 

o Identification of possible interactions of medications to treat 
alcoholism and concurrent psychiatric conditions as well as 
interactions with alcohol.  Pharmacokinetic studies might also be 
appropriate.  For example, Ciraulo et al. (1982) demonstrated that at a 
given dose of imipramine, patients who were both alcoholic and 
depressed attained lower blood levels of the medication than 
nonalcoholic depressed subjects.

MECHANISM(S) OF SUPPORT 

This PA will use the NIH research project grant (R01) small grant (R03) 
and exploratory/developmental grant (R21) award mechanism.  As an 
applicant, you will be solely responsible for planning, directing, and 
executing the proposed project. The total project period for a research 
project grant (R01) application submitted in response to this Program 
Announcement may not exceed 5 years.  Exploratory/developmental grants 
(R21) are limited to 3 years for up to $100,000/year for direct costs. 
(See Program Announcement PA- 99-131, "NIAAA Exploratory/Developmental 
Grant Program," https://grants.nih.gov/grants/guide/pa-files/PA-99-131.html, 
for a complete description of the R21 mechanism.)

Under the NIAAA Small Grant mechanism (R03) applicants may request 
either $25,000 or $50,000 in direct costs per year for up to two years.  
These awards are not renewable; however, a no-cost extension
of up to one year may be granted to the grantee institution prior to 
expiration of the project period. Before completion of the R03, 
investigators are encouraged to seek continuing support for research 
through a research project grant (R01).  (See Program Announcement PA-
99-098, "NIAAA Small Grant Program," 
https://grants.nih.gov/grants/guide/pa-files/PAR-99-098.html, for a 
complete description of the R03 mechanism.)
    
This PA uses just-in-time concepts.  It also uses the modular as well 
as the non-modular budgeting formats (see 
https://grants.nih.gov/grants/funding/modular/modular.htm).  
Specifically, if you are submitting an application with direct costs in 
each year of $250,000 or less, use the modular format.  Otherwise 
follow the instructions for non-modular research grant applications.

ELIGIBLE INSTITUTIONS 

You may submit (an) application(s) if your institution has any of the 
following characteristics:
	
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
o Faith-based organizations

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support.  Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.
 
WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the 
opportunity answer questions from potential applicants.  Inquiries may 
fall into three areas:  scientific/research, peer review, and financial 
or grants management issues:

o Direct your questions about scientific/research issues to:

Charlene E. LeFauve, Ph.D.
Division of Clinical and Prevention Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulvard, Suite 505 MSC 7003
Bethesda, MD  20892-7003
For express mail use:
Rockville, MD  20852)
Telephone:  (301) 402-9401
Fax:  (301) 443-8774
Email:  clefauve@NIAAA.nih.gov

o Direct your questions about financial or grants management matters to:

Judy Fox Simons
Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulvard, Suite 505 MSC 7003
Bethesda, MD  20892-7003
(For express mail use:
Rockville,MD  20852)
Telephone:  (301) 443-2434
Email:  jsimons@niaaa.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at https://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email:  GrantsInfo@nih.gov.

APPLICATION RECEIPT DATES: Applications submitted in response to this 
program announcement will be accepted at the standard application 
deadlines, which are available at 
https://grants.nih.gov/grants/dates.htm.  Application deadlines are also 
indicated in the PHS 398 application kit.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications 
requesting up to $250,000 per year in direct costs must be submitted in 
a modular grant format.  The modular grant format simplifies the 
preparation of the budget in these applications by limiting the level 
of budgetary detail.  Applicants request direct costs in $25,000 
modules.  Section C of the research grant application instructions for 
the PHS 398 (rev. 5/2001) at 
https://grants.nih.gov/grants/funding/phs398/phs398.html includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at 
https://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER 
YEAR: Applications requesting $500,000 or more in direct costs for any 
year must include a cover letter identifying the NIAAA staff member who 
has agreed to accept assignment of the application.   

Applicants requesting more than $500,000 must carry out the following steps:
	
1)	Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2) Obtain agreement from the IC staff that the IC will accept your 
application for consideration for award; and,
  
3) Identify, in a cover letter sent with the application, the staff 
member and IC who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), 
competing continuation (type 2), competing supplement, or any amended 
or revised version of these grant application types. Additional 
information on this policy is available in the NIH Guide for Grants and 
Contracts, October 19, 2001 at 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the checklist, and five signed 
photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING: Applications must be received by or mailed 
before the receipt dates described at 
https://grants.nih.gov/grants/funding/submissionschedule.htm.  The CSR 
will not accept any application in response to this PA that is 
essentially the same as one currently pending initial review unless the 
applicant withdraws the pending application.  The CSR will not accept 
any application that is essentially the same as one already reviewed.  
This does not preclude the submission of a substantial revision of an 
application already reviewed, but such application must include an 
Introduction addressing the previous critique.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review 
group convened in accordance with the standard NIH peer review 
procedures (http://www.csr.nih.gov/refrev.htm) will evaluate 
applications for scientific and technical merit.

As part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a selection process in which only those applications deemed 
to have the highest scientific merit, generally the top half of 
applications under review, will be discussed and assigned a priority score
o Receive a second level review by the appropriate national advisory 
council or board
	
REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to discuss the 
following aspects of your application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The scientific review group will address and consider each of these 
criteria in assigning your application's overall score, weighting them 
as appropriate for each application.  Your application does not need to 
be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
you may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

(1) SIGNIFICANCE:  Does your study address an important problem? If the 
aims of your application are achieved, how do they advance scientific 
knowledge?  What will be the effect of these studies on the concepts or 
methods that drive this field?

(2) APPROACH:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Do you acknowledge potential problem areas and 
consider alternative tactics?

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project 
challenge existing paradigms or develop new methodologies or technologies?

(4) INVESTIGATOR: Are you appropriately trained and well suited to 
carry out this work?  Is the work proposed appropriate to your 
experience level as the principal investigator and to that of other 
researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your work 
will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements?  Is there 
evidence of institutional support?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed with respect to the following:

PROTECTIONS:  The adequacy of the proposed protection for humans, 
animals, or the environment, to the extent they may be adversely 
affected by the project proposed in the application.

INCLUSION:  The adequacy of plans to include subjects from both 
genders, all racial and ethnic groups (and subgroups), and children as 
appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects will also be evaluated. (See 
Inclusion Criteria included in the section on Federal Citations, below)

BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.
 
AWARD CRITERIA

Applications submitted in response to a PA will compete for available 
funds with all other recommended applications.  The following will be 
considered in making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research 
components involving Phase I and II clinical trials must include 
provisions for assessment of patient eligibility and status, rigorous 
data management, quality assurance, and auditing procedures.  In 
addition, it is NIH policy that all clinical trials require data and 
safety monitoring, with the method and degree of monitoring being 
commensurate with the risks (NIH Policy for Data Safety and Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 
https://grants.nih.gov/grants/guide/notice-files/not98-084.html).

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy 
of the NIH that women and members of minority groups and their sub-
populations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided 
indicating that inclusion is inappropriate with respect to the health of 
the subjects or the purpose of the research. This policy results from 
the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the AMENDMENT 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at 
https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.  
The amended policy incorporates: the use of an NIH 
definition of clinical research; updated racial and ethnic categories 
in compliance with the new OMB standards; clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398; and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic 
group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN 
SUBJECTS:  The NIH maintains a policy that children (i.e., individuals 
under the age of 21) must be included in all human subjects research, 
conducted or supported by the NIH, unless there are scientific and 
ethical reasons not to include them. This policy applies to all initial 
(Type 1) applications submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the inclusion of children as 
participants in research involving human subjects that is available at 
https://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  
NIH policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: 
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom 
of Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at 
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and 
proposals for NIH funding must be self-contained within specified page 
limitations. Unless otherwise specified in a NIH solicitation, Internet 
addresses (URLs) should not be used to provide information necessary to 
the review because reviewers are under no obligation to view the 
Internet sites.   Furthermore, we caution reviewers that their 
anonymity may be compromised when they directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2010," a PHS-led national activity for setting priority 
areas. This PA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93.273, and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.  Awards are made under authorization of 
Sections 301 and 405 of the Public Health Service Act as amended (42 
USC 241 and 284) and administered under NIH grants policies described 
at https://grants.nih.gov/grants/policy/policy.htm and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in some cases, any portion of a 
facility) in which regular or routine education, library, day care, 
health care, or early childhood development services are provided to 
children.  This is consistent with the PHS mission to protect and 
advance the physical and mental health of the American people.

REFERENCES

Brown, R.A., and Ramsey, S.E. (2000).  Addressing comorbid depressive 
symptomatology in alcohol treatment.  Professional Psychology: Research 
and Practice 31:418-422.

Brown, R.A., Evan, D.M., Miller, I.W., Burgess, E.S., and Mueller, T.I. 
(1997).  Cognitive—behavioral treatment for depression in alcoholism.  
Journal of Consulting and Clinical Psychology 65:715-726.

Ciraulo, D.A., Alderson, L.M., Chapron, D.J., Jaffe, J.H., Subbarao, 
B., and Kramer, P.A. (1982).  Imipramine disposition of alcoholics.  
Journal of Clinical Psychopharmacology 2:2-7.

Cornelius, J.R., Salloum, I.M., Ehler, J.G., Jarrett, P.J., Cornelius, 
M.D., Perel, J.M., Thase, M.E., and Black, A. (1997).  Fluoxetine in 
depressed alcoholics.  Archives of General Psychiatry 54:700-705.

Cornelius, J.R., Salloum, I.M., Mezzich, J., Cornelius, M.D., Jr., 
Fabrega, H., Ehler, J.G., Ulrich, R.F., Thase, M.E., and Mann, J.J. 
(1995).  Disproportionate suicidality in patients with comorbid major 
depression and alcoholism.  The American Journal of Psychiatry 152:358-364. 

Drake, R.E., Xie, H., McHugo, G.J., and Green, A.I. (2000).  The 
effects of clozapine on alcohol and drug use disorders among patients 
with schizophrenia.  Schizophrenia Bulletin 26: 441-449.

Drake, R.E., and Mueser, K.T. (1996).  Alcohol-use disorder and severe 
mental illness.  Alcohol Health and Research World 20:87-93.

Grant, B.F. and Harford, T.C. (1995). Comorbidity between DSM-IV 
alcohol use disorders and major depression: Results of a national 
survey.  Drug and Alcohol Dependence 39: 197-206.

Greenfield, S.F., Weiss, R.D., Muenz, L.R., Vagge, L.M., Kelly, J.F. 
Bello, L.R., and Michael, J. (1998).  The effect of depression on 
return to drinking: A prospective study.  Archives of General 
Psychiatry 55:259-265.

Helzer, J.E., and Pryzbeck, T.R. (1988).  The co-occurrence of 
alcoholism with other psychiatric disorders in the general population 
and its impact on treatment.  Journal of Studies on Alcohol 49:219-224.

Kessler, R.C., Nelson, C.B., McGonagle, K.A., Edlund, M.J., Frank, 
R.G., and Leaf, P.J. (1996).  The epidemiology of co-occurring 
addictive and mental disorders: Implications for prevention and service 
utilization.  American Journal of Orthopsychiatry 66:17-31.

Kranzler, H.R., Burleson, J.A., Del Boca, F.K., Babor, T.F., Korner, 
P., Brown, J., and Bohn, M.J. (1994).  Buspirone treatment of anxious 
alcoholics: A placebo-controlled trial.  Archives of General Psychiatry 
51:720-731.

Malcom, R., Anton, R.F., Randall, C.L., Johnston, A., Brady, K., and 
Thevos, A. (1992).  A placebo-controlled trial of buspirone in anxious 
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