COMBINED PHARMACOTHERAPY IN DEPRESSED ALCOHOLICS

我们拟在一项双盲、安慰剂对照、随机、平行组试验中，检验纳洛酮和氟西汀联合治疗与氟西汀单药治疗酒精中毒和合并重度抑郁症患者的疗效。美国有近800万人受到影响，酒精中毒和严重抑郁症共病是一个严重的公共卫生问题。合并症的存在对治疗反应和结果有显著的负面影响，导致自杀风险增加和昂贵的住院精神病护理率增加。缺乏有效的药物治疗来解决这两种疾病。在评价抗抑郁药单药治疗抑郁症酗酒者的研究中，仅获得部分应答。我们以前的工作与SSRI氟西汀已经证明了积极的结果发表到目前为止，在严重抑郁的酗酒者。我们以前的工作与SSRI氟西汀已表明最积极的结果发表到目前为止，在严重抑郁症酗酒者。然而，该研究中的氟西汀组仅显示出部分治疗反应，戒断率低，抑郁症状和酒精滥用持续存在。然而，我们最初的和扩展的试点工作，评估联合纳洛酮和氟西汀的有用性，表明一个强大的反应，与酒精使用和抑郁症状显着减少。我们对这两种药物之间潜在相互作用的研究表明，纳洛酮不会增加大多数患者的氟西汀或去甲氟西汀血药浓度。我们提出的研究将建立在我们以前的工作和建立的记录，在这个复杂的和高风险的人群中进行药物疗效试验，并在开发必要的基础药理学方法，以调查拟议的地毯相互作用研究。这种合并症的高患病率以及联合药物治疗在临床实践中的广泛但未经检验的使用强调了我们提出的研究的及时性。因此，我们的研究将填补我们在高风险临床人群治疗方面的知识空白。我们假设氟西汀和纳洛酮联合治疗将为合并重度抑郁症的酗酒者提供更好的治疗。氟西汀除了针对与酒精中毒相关的强迫性消费行为外，还将针对抑郁症，而纳洛酮将针对与病理性酒精使用相关的积极强化作用和释放风险。我们要求五年的支持，以实现以下目标：1）检查纳洛酮加氟西汀与氟西汀和安慰剂相比，在治疗患有DSM-IV酒精依赖和单相重性抑郁症的患者中的疗效。2)评估药物反应的特定预测因素; 3）对持续性抑郁症状对酒精使用的影响进行前瞻性评估。在为期6个月的双盲研究和为期6个月的治疗后随访阶段，将对106名急性抑郁和主动饮酒的受试者进行随机化和前瞻性随访。

We propose to test the efficacy of the combination of naltrexone and fluoxetine versus fluoxetine alone in the treatment of patients with alcoholism and co-morbid major depression in a double-blind, placebo- controlled, randomized, parallel group trial. With nearly eight million affected individuals in the U.S., co-morbid alcoholism and major depressive disorder represent a significant public health problem. The presence of co-morbidity has a significant negative impact on treatment response and outcome, resulting in increased risk for suicide and increased rates of costly inpatient psychiatric care. Effective pharmacologic treatments addressing thee dual disorders are lacking. Only partial response has been obtained in studies evaluating anti- depressant monotherapy in depressed alcoholics. Our previous work with the SSRI fluoxetine has demonstrative the positive results published to date in severely depressed alcoholics. Our previous work with the SSRI fluoxetine has demonstrative the most positive results published to date in severely depressed alcoholics. The fluoxetine group in that study, however, displayed only a partial treatment response, with low abstinence rates and persistent depressive symptoms and alcohol abuse. However, our original and extended pilot work evaluating the usefulness of combined naltrexone and fluoxetine suggest a robust response, with a significant decrease in alcohol use and depressive symptoms. Our study of potential interactions between these two medications documents that naltrexone does not increase fluoxetine or norfluoxetine blood levels in most patients. Our proposed study will build on our previous work and established record both in conducting medication efficacy trials in this complex and high risk population, and in developing fundamental pharmacological methodologies necessary to investigate the proposed rug interaction studies. The timeliness of our proposed study is underscored by the high prevalence of this co-morbid condition and by the widely but untested use of the combined medication treatment in clinical practice. Thus, our study our will fill an important gap in our knowledge regarding the treatment of high risk clinical population. We hypothesize that combined fluoxetine and naltrexone treatment will offer enhanced treatment for alcoholics with co-morbid major depression. While the fluoxetine will target the depressive disorders in addition to the compulsive consumatory behavior related to alcoholism, the naltrexone will target the positive reinforcing effect and release risk related to pathological alcohol use. We request five years of support to achieve the following aims: 1) Examine the efficacy of naltrexone plus fluoxetine compared to fluoxetine and placebo in the treatment of patients with co- morbid DSM-IV alcohol dependence and unipolar major depression.; 2) Assess specific predictors of medication response; 3) Conduct a prospective assessment of the effect of persistent depressive symptoms on alcohol use. One hundred and six acutely depressed and actively drinking subjects will be randomized and prospectively followed during a 6 month double-blind study, and a 6-month post-treatment follow-up phase.