Clinical Psychopharmacology

Alexander H. Glassman, M.D., Chief of Psychiatric Research
B. Timothy Walsh, MD, Psychiatrist II
Steven P. Roose, MD, Psychiatrist Research II
Lirio S. Covey, Ph.D., Research Scientist V
Michael J. Devlin, MD, Psychiatrist II
Juli A. Goldfein, Ph.D., Instructor of Clinical Psychology
Evelyn Attia, M.D, Psychiatrist II
Laurel Meyer, M.D., Assistant Professor of Clinical Psychiatry
Pamela Raizman, Ph.D., Instructor of Clinical Psychology
Stuart Seidman, M.D., Assistant Professor of Clinical Psychiatry
Sara Wolk, Ph.D., Instructor of Clinical Psychology
Ellen Zimmerli, PhD., Assistant Clinical Professor

OVERVIEW
Our research efforts have focused on depression, reward systems and their comorbidity. Areas of interest include: biological characteristics and treatment modalities in patients with late-life depression; the relationship of depression to the development of cardiac disease and to mortality/morbidity in heart attack, unstable angina, and coronary artery bypass patients; pharmacological and psychological treatment of eating disorders; psychological concomitants of and risk factors for eating disorders; and smoking dependence, with special interest in the relationship between nicotine addiction and depression, as well as the prevention of smoking relapse.

CURRENT RESEARCH
Late Life Depression Center The Late Life Depression Center was established in 1991 by the Departments of Clinical Psychopharmacology and Biological Psychiatry to focus on the study of the phenomenology, biology, and treatment of depressed older adults. The Center is the only research clinic focusing on depression in the elderly in New York City. Depression is a common illness in this growing segment of the population and research efforts have not been commensurate with the public health significance of the disorder. Studies have demonstrated that a mild, chronic type of depression, called dysthymia, occurs in older patients, and initial trials have suggested that medication may be of help to these patients. One of the unique studies conducted at the Center compared the efficacy of a tricyclic antidepressant to a serotonin reuptake inhibitor in elderly patients with ischemic heart disease. This study established that for these patients, an SSRI is equally effective and a safer treatment than a TCA. Current federally funded projects in the Center include studies of the effectiveness of antidepressant medications in older adults; cerebrovascular abnormalities in late-onset depression; elderly, depressed cognitively impaired patients; cerebral blood flow in elderly depressed patients; and the effectiveness of testosterone replacement as a treatment for depression in men. The Center was also the lead site in the first multi-center study of treatment of depression in the old-old, i.e., patients over 80. For the past six years the Center has been a training site for the development of clinical researchers in geriatric psychiatry and this effort is supported by a NIMH training grant. Recently completed study documents that severe form of depression called melancholia does not respond well to treatment with most popular antidepressant medications called SSRIs.

Current studies focus on the treatment of patients with depression and cognitive impairment and the treatment of atypical depression.

Antidepressant Studies In Patients With Ischemic Heart Disease There are significant data to support the observation that depression dramatically increases the risk of dying following a myocardial infarction or unstable angina. However, it has been uncertain if using antidepressant drugs after a heart attack is safe and their efficacy in reducing the associated increase in mortality was unclear. We have recently completed a large multi-site study of the safety and efficacy of sertraline immediately following an infarction or unstable angina. Drug treatment proved to be both safe and effective, and there was a strong suggestion that morbidity and mortality was reduced. This study was published in the Journal of the American Medical Association. Efforts are now underway to obtain funding to do a definitive study testing whether these drugs will reduce mortality in depressed with acute coronary disease.

Study and Treatment of Nicotine Dependence
Smoking Cessation and Relapse Prevention We are continuing our work in drug development and extending our research to better understand genetic and other biological factors that contribute to nicotine dependence. Advances in tobacco dependence treatment have resulted in a number of efficacious therapies for smokers who wish to stop smoking. These treatments, however, which are typically four to eight weeks in duration, have not solved the problem of a high relapse rate associated with tobacco cessation. Through a 5-year grant funded by the National Institute on Drug Abuse (NIDA), we are entering over 700 moderate-to-heavy smokers in a 12-month study to determine the efficacy of maintenance pharmacotherapy for reducing the rate of relapse to smoking. This study will enable us to determine which combination of pharmacotherapy (bupropion, nicotine replacement, or the combination) will best reduce the relapse rate. In addition, we are studying the demographic, psychological, personality, and psychiatric factors that influence cessation and relapse, and measure the cost-effectiveness of each type of maintenance treatment.

Smokers of Racial/ethnic Minority Background Most of the available information regarding nicotine dependence and treatment has been obtained from predominantly Caucasian populations. We are extending the knowledge base to other racial/ethnic groups, through supplementary funds from NIDA to study: a) the nature of nicotine dependence, b) those factors influencing successful cessation using bupropion, nicotine patch, and counseling, and c) the efficacy of long-term use of pharmacotherapy with Hispanic, African-American, and Asian smokers.

International Tobacco Research Through additional funding from NIDA, the parent maintenance study is being replicated in the Philippines, a country that has one of the highest rates of smoking. This study is being conducted with investigators from the Departments of Psychiatry and Pulmonology at the School of Medicine of the University of the Philippines.

Smoking Reduction: an Alternative Treatment Goal for Nicotine Dependent Smokers
We have begun a new study that is expected to provide additional knowledge about the nature of nicotine dependence and new strategies for nicotine dependence treatment. Despite the availability of efficacious treatments, many smokers are unwilling or unable to achieve complete cessation, rendering them at continued high risk for tobacco-related morbidity and mortality. Tobacco harm reduction (THR) through reduced tobacco exposure has increasingly received attention as an alternative treatment goal for these smokers. In a new study, we will explore the feasibility, sustainability, and health effects of smoking reduction. A sample of female African-American and Caucasian smokers who were unable to stop smoking in the parent maintenance treatment study will be entered. This study is funded by the National Cancer Institute. We are collaborating with investigators from the Graduate Center of the City University of New York and the Institute for Cancer Prevention in Valhalla, New York.

Genetic Factors in Nicotine Dependence With researchers from the Medical Genetics Department, we are continuing a 5-year study funded by the National Institute on Drug Abuse to conduct a genetic linkage study to identify and locate genetic risk factors for persistent smoking. DNA and clinical data are collected from same sex-sibling pairs both of whom have a history of persistent smoking and meet criteria for nicotine dependence.

Training We have begun an affiliation with the Center for Applied Public Health Research at the School of Public Health, Columbia University. Through funding provided by the American Legacy Foundation a network of Columbia University tobacco researchers provides mentoring to junior investigators and doctoral students planning a research career in nicotine and tobacco research.

Treatment and Psychobiological Concomitants of Bulimia Nervosa, Anorexia Nervosa, and Binge Eating Disorder
Bulimia Nervosa In the past year, we have published two studies which inform our treatment of Bulimia Nervosa. One study documented the utility of antidepressant medication for adolescents with bulimia, and a separate study found that, in a primary care setting, antidepressant medication, but not a self-help program, was more useful than general medical care. In addition, we are continue work aimed at examining some of the psychobiological concomitants of bulimia nervosa: eating behavior, stomach functioning, and levels of CCK, a hormone that is released into the blood after eating to signal "fullness,” and received another five years of funding to support this work. We continue a collaborative, translational research grant among several groups studying various aspects of eating regulation: researchers studying drug abuse/dependence (Dr. Richard Foltin), researchers studying peripheral controls of appetite and satiety in animals (Drs. Norcross Geary, Gary Schwartz, and Gerard Smith), and CNS reward mechanisms involved in eating (i.e. “sugar addiction”) in animals (Dr. Bart Hoebel). The purpose of this grant is to apply the concepts and methodology used by these other groups to study dysregulation of eating in humans.

Anorexia Nervosa We have completed and published a study documenting that cognitive behavioral therapy (CBT) is more effective than nutritional counseling in preventing post-hospitalization relapse among patients recently treated for Anorexia Nervosa. We will soon complete, in collaboration with colleagues in Toronto, the largest study of medication in the treatment of this potentially devastating illness. We have recently initiated a controlled evaluation of atypical antipsychotic medication in this disorder. In addition to these treatment-based investigations, we are conducting studies that examine some of the psychobiological concomitants of Anorexia Nervosa. One study aims to measure serotonin activity in women with anorexia nervosa undergoing re-feeding. Another study examines changes in body composition, metabolic rate, and hormone levels in women with anorexia at low weight and after weight has normalized. The above mentioned translational research grant is examining the phenomenon of exercise dependence in women with anorexia nervosa.

Binge Eating Disorder We have recently completed the follow-up phase of a controlled treatment study to determine the relative and additive efficacy of two contrasting treatments for women and men with Binge Eating Disorder who participate in standard group behavioral weight-control treatment: individual CBT and antidepressant medication. We are participating in a multicenter study of the efficacy of topiramate in treating binge eating disorder. We are continuing to conduct laboratory studies of eating behavior in obese women with and without binge eating disorder. Finally, we have begun to study the relationship between eating disorders, such as binge eating and night eating, and outcome in patients who have gastric bypass surgery for obesity.

EDUCATION AND TRAINING
The unit staff is active in a broad range of training programs. The educational objectives for all residents are to learn how to recognize and treat major depression and eating disorders and the principles of pharmacology that govern the use of psychotropic medications.

PATIENT CARE
The 5th Floor Clinical Service is a research unit devoted to, among other things, the study and treatment of eating disorders. Treatment modalities include antidepressant medication and cognitive behavior therapy.

SPECIAL ACTIVITIES
In addition to regional seminars in psychopharmacology, the department administers a statewide psychopharmacology "Hotline." This is a service offered to NYS DMH facilities across the state through which physicians may, by phone, get immediate expert advice on any drug related psychiatric problem. It functions to improve the level of patient care throughout the New York State psychiatric system.

BIBLIOGRAPHY