Optimizing Pharmacotherapy for Bipolar Alcoholics

优化双相酗酒者的药物治疗

• 批准号: 7368095
• 负责人: IHSAN M SALLOUM
• 金额: $ 50.05万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7368095
• 关键词: Abstinence; Acute; Address; Adherence; Adult; Advocate; Affect; Age of Onset; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Anxiety Disorders; Applications Grants; Area; Bipolar Disorder; Clinical; Combined Modality Therapy; Comorbidity; Controlled Study; Counseling; DSM-IV; Depressed mood; Diagnosis; Disease; Double-Blind Method; Drug Addiction; Evaluation; Evidence based treatment; Frequencies; General Population; Hand; Heavy Drinking; Hospitalization; Individual; Intervention; Label; Maintenance; Major Depressive Disorder; Manic; Mediating; Mediator of activation protein; Mental disorders; Moods; Morbidity - disease rate; NIH Program Announcements; Naltrexone; Naltrexone hydrochloride; Narcotic Antagonists; National Institute of Drug Abuse; National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; Opioid; Outcome; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Pilot Projects; Placebo Control; Placebos; Population; Psychiatry; Psychopathology; Public Health; Publishing; Randomized; Randomized Controlled Trials; Rate; Recruitment Activity; Recurrence; Relapse; Research; Research Personnel; Research Proposals; Rest; Review Literature; Risk; Schizophrenia; Severities; Social support; Stabilizing Agents; Stress; Substance Use Disorder; Substance abuse problem; Symptoms; Syndrome; System; Testing; Therapeutic; Time; Valproate Sodium; Week; Woman; Work; addiction; alcohol abstinence; alcohol abuse therapy; alcohol effect; base; compliance behavior; craving; day; depressive symptoms; design; desire; disability; disorder later incidence prevention; drinking; dual diagnosis; efficacy trial; experience; follow-up; improved; medication compliance; men; mortality; placebo controlled study; problem drinker; prospective; response; suicidal risk; therapy adherence; valproate

This is a revision of application 1 R01 AA015385-01 that focuses on the evaluation of a promising pharmacological intervention for patients with alcoholism complicated by comorbid bipolar disorder, an area of major unmet treatment needs. We propose a double-blind, placebo-controlled, randomized, parallel group trial to test the efficacy of the combination of the opioid antagonist, naltrexone, and the antikindling mood stabilizing agent valproate, versus valproate alone, in the treatment of patients with comorbid alcoholism and bipolar disorder. With nearly two million affected individuals in the U.S., comorbid alcoholism and bipolar disorder represents a significant public health challenge. This comorbidity is associated with severe disability, morbidity, and heightened risk for suicide. Surprisingly, little research and limited evidence-based treatment options exist for this high-risk population. Our recently published randomized controlled trial of valproate efficacy in bipolar alcoholics remains the only such study completed to date (Arch Gen Psychiatry 2005; 62:37-45). The results of that study suggested an advantage of valproate over placebo in reducing heavy alcohol use. However, a significant proportion of valproate treated subjects continued to consume alcohol at abusive levels. There are compelling theoretical, and accruing clinical evidence suggesting that combined valproate + naltrexone may have synergistic effects on decreasing alcohol use. Valproate, may decrease alcohol use by stabilizing pathological mood states, and by dampening the negative reinforcing effects of acute and protracted alcohol withdrawal. Conversely, naltrexone would decrease the positive reinforcing effects of alcohol by decreasing the desire to drink alcohol. The results of our open-label, randomized, pilot study suggests that valproate + naltrexone robustly enhances abstinence from alcohol, decreases craving, and improves mood and functioning. All are particularly desirable outcomes in patients suffering from severe psychopathology. These results provide compelling evidence for testing this approach in a randomized, controlled trial. We propose the following aims: 1) Examine the efficacy of naltrexone plus valproate compared to valproate and placebo in the treatment of patients with DSM-IV alcohol dependence and comorbid bipolar I disorder; 2) Assess the effects of primary vs. secondary alcoholism, bipolar subtype (depressed vs. manic/mixed subtype), and the presence of another substance use disorder (SUD) as moderators of alcohol use outcome; 3) Assess the effects of medication compliance, persistence of mood symptoms or SUD, and social support as mediators of alcohol use outcome. One hundred and four acutely ill and actively drinking adult subjects will be randomized and prospectively followed during a 3-month double-blind study, and a 3-month follow-up phase. All subjects will receive individual counseling designed to enhance treatment adherence.

这是对申请1 R01 AA015385-01的修订，重点是对有前途的药物进行评估