PHARMACOLOGICAL AND PSYCHOLOGICAL METHODS IN THE EXECUTION OF THE COMBINE TRIAL
Co-Chairs: Bankole A. Johnson, D.Sc., M.D., Ph.D., and Allen Zweben, D.S.W.
Introduction
Neuroscientific progress on the biological underpinnings of alcohol-seeking behavior has heralded the development of pharmacological treatments for alcohol dependence. While earlier studies simply tested medications against a platform of standardized psychosocial treatment, there has been the growing realization that both medications and the psychosocial treatments have unique dose-response relationships that can interact within a clinical trial. Indeed, the most efficacious combination of medication and psychosocial treatment need not be the highest or most intense “dose” of both. Further, extrapolating from a research trial to clinical practice requires the measurement of not only efficacy but therapeutic effectiveness in terms of adherence and process interactions between the “dose” of pharmacotherapy and psychosocial treatment. In a twopronged presentation at this RSA meeting, COMBINE investigators first will provide a symposium on efficacy for the combined interactions of two pharmacotherapies (i.e., the mu-opioid antagonist naltrexone and the glutamate antagonist acamprosate) and two psychosocial treatments varying in minimum to maximum intensity (i.e., medication management and cognitive behavioral intervention). In this second presentation, COMBINE investigators will provide a workshop on the measurement of therapeutic effectiveness for the same trial. Together, these presentations will provide an integrated understanding of the scientific and ecological validity of this combined pharmacological and psychosocial treatment toward optimizing the management of alcohol dependence.
Acamprosate — Dosing and Adherence, by Barbara J. Mason, Ph.D.
Acamprosate has been used successfully in Europe for over a decade in the treatment of alcohol dependence. Recently approved by the Food and Drug Administration (FDA), this medication has been found to stabilize the glutamate-NMDA system during protracted withdrawal. Its use has been associated with relatively few adverse events; long-term studies have demonstrated efficacy at promoting abstinence. In this presentation, I shall outline the factors associated with medication compliance with acamprosate. Specifically, I shall examine dose and treatment adherence to acamprosate and how this is affected by the different intensities of psychotherapy. Factors associated with increased medication compliance and how this might translate from research trials to clinical practice will be discussed. Finally, I shall compare and contrast the treatment adherence results of acamprosate in COMBINE with other peer-reviewed studies.
Naltrexone — Dosing and Adherence, by Robert M. Swift, M.D., Ph.D., and Domenic A. Ciraulo, M.D.
The mu-opioid antagonist, naltrexone, was approved by the FDA for the treatment of alcohol dependence more than a decade ago and is utilized for that indication in about 30 other countries. Meta-analytic studies have consistently demonstrated efficacy for naltrexone, especially with the target of reducing heavy drinking. Nevertheless, some naltrexone trials have had difficulty finding efficacy due to less than optimal (<85%) medication compliance. In this presentation, we shall outline the processes and procedures utilized to maximize compliance with naltrexone treatment. Further, we shall outline how compliance is affected by psychosocial treatment intensity as well as patientrelated bio-psychosocial factors. Factors associated with increased medication compliance and how this might translate from research trials to clinical practice will be discussed. Finally, we shall compare and contrast the treatment adherence results of naltrexone in COMBINE with other peer-reviewed studies.
Medical Management in the Treatment of Alcohol Dependence: A Psychosocial Intervention that Supports Pharmacotherapy, by Helen M. Pettinati, Ph.D.
A structured, medically based intervention, called Medical Management (MM), was designed by experts in the field of alcoholism to be used when pharmacotherapy is given as part of the treatment for alcohol dependence. MM was developed as part of the NIAAA-supported COMBINE multi-site national study, which investigated combining pharmacotherapy and psychosocial interventions to treat alcohol dependence. MM is constructed to be implemented by medically trained practitioners in non-specialty settings, and it incorporates into each visit evaluations of medication safety and adherence, as well as monitoring alcohol use. The information from these evaluations then comprises the clinician’s individualized feedback and direct advice to the patient at that visit.
There are several principal themes in MM treatment. One theme is the education that the clinician provides to the patient — about the disorder, how it has manifested or might manifest itself in the specific patient, and what treatment options are available. As part of this education, the pharmacotherapy to be used is fully explained by the clinician. That is, information is provided on how to take the medication(s) as prescribed, what the patient should expect from the medication(s), and what kinds of events the clinician will need to know about while the patient is in treatment. Another focus in MM treatment is to discuss strategies with the patient for ensuring medication safety and adherence to taking what is prescribed. MM is delivered best when the clinician provides the patient maximum support and optimism for recovery. In this presentation, I shall detail the MM intervention, its implementation, and supportive data collected as part of the COMBINE study. Additionally, I shall examine the critical and functional processes associated with MM and with medication compliance, thereby providing practical information on the translation of MM from research trials to clinical practice.
The Application of Combined Behavioral Intervention in a Combined Pharmacotherapy and Behavioral Treatment Trial, by Allen Zweben, D.S.W.
In this presentation, I shall examine a number of issues pertaining to combined behavioral intervention (CBI), a state-of-the-art treatment approach employed in the COMBINE Study. CBI is a moderately intensive behavioral intervention that integrates several evidence-based treatment methods employed previously in Project MATCH and other clinical trials. Unlike behavioral therapies employed in earlier trials, CBI allows for normal clinical flexibility in terms of the number and spacing of sessions and provides a menu of options for participants to choose treatment components most relevant to their individual needs (e.g., assertiveness skill training and mood management). Additionally, pull-out procedures are employed to address special needs of participants (e.g., case management) as they often arise during the course of therapy. Also in this presentation, I shall examine and detail COMBINE findings on therapist fidelity and participant adherence. Specifically, how do differences found in session attendance and use of various components of the model impact on treatment outcome? Finally, I shall place the use of CBI as a behavioral platform for pharmacotherapy in the context of other psychosocial interventions.
Panel Discussion: Integration of Pharmacotherapy and Counseling into Primary Care Settings, by Bankole A. Johnson, Barbara J. Mason, Helen M. Pettinati, Robert M. Swift, Domenic A. Ciraulo, and Allen Zweben
General medical practice manages a wide variety of chronic disorders in coordination with specialty treatment such as diabetes, HIV, congestive heart failure, and depression. Yet, primary care settings have generally avoided managing the care of individuals with chronic alcohol problems. Given the drastic reduction of specialty treatment for alcohol problems, there is a need to expand opportunities to address alcohol use disorders within nonspecialty or health care settings. Recent advances in medications and behavioral therapies have provided new opportunities to manage the care of serious alcohol use disorders in these settings. Having access to effective medications and counseling could transform the practice of community treatment for alcohol dependence.
PARTICIPANT LIST
Bankole A. Johnson, D.Sc., M.D., Ph.D., Alumni Professor of Psychiatric Medicine and Professor of Neuroscience; Chairman, Department of Psychiatric Medicine, University of Virginia, P.O. Box 800623, Charlottesville, VA 22908-0623. Telephone: 434-924-5457. Fax: 434-244-7565. E-mail: .
Allen Zweben, D.S.W., Professor and Associate Dean for Research and Sponsored Projects, School of Social Work, Columbia University, 1255 Amsterdam Avenue, Room 829, New York, NY 10027. Telephone: 212-851-2387. Fax: 212-851-2005. E-mail: .
[PowerPoint projector and laptop.]
Barbara J. Mason, Ph.D., Professor, Molecular and Integrative Neurosciences Department; Director, Laboratory of Clinical Psychopharmacology; Co-Director, Pearson Center for Alcoholism and Addiction Research, The Scripps Research Institute, 10550 N. Torrey Pines Road, TPC-5, La Jolla, CA 92037. Telephone: 858-784-7324. Fax: 858-784-7340. E-mail: .
Robert M. Swift, M.D., Ph.D., Professor, Department of Psychiatry and Human Behavior, Brown University Medical School; Associate Chief of Staff for Research, Providence VA Medical Center; 830 Chalkstone Avenue, Providence, RI 02908. Telephone: 401-457-3066. Fax: 401-457-3305. E-mail: .
Domenic A. Ciraulo, M.D., Professor and Chairman, Division of Psychiatry, Boston University School of Medicine, 720 Harrison Avenue, Suite 914, Boston, MA 02118. Telephone: 617-638-8141. E-mail: .
Helen M. Pettinati, Ph.D., Professor, Department of Psychiatry; Director, Treatment Research Division, Center for Studies of Addiction, University of Pennsylvania, 3900 Chestnut Street, Philadelphia, PA 19104-6178. Telephone: 215-222-3200, ext. 139. Fax: 215-386-6770. E-mail: .
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