1/4-Sustaining Remission of Psychotic Depression

1/4-精神病性抑郁症的持续缓解

• 批准号: 8650921
• 负责人: BARNETT MEYERS
• 金额: $ 45.16万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-06 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8650921
• 关键词: Acute; Address; Adverse effects; Age; Antidepressive Agents; Antipsychotic Agents; Benefits and Risks; Cholesterol; Clinical; Collaborations; Combined Modality Therapy; Disease; Disease remission; Double-Blind Method; Drug Kinetics; Elderly; Electroconvulsive Therapy; Exposure to; Funding; Genetic Polymorphism; Goals; Guidelines; Hypertriglyceridemia; Impaired cognition; Inpatients; Leadership; Lipids; Major Depressive Disorder; Mental Depression; Mental disorders; Metabolic; Morbidity - disease rate; National Institute of Mental Health; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Placebos; Population; Prevalence; Principal Investigator; Public Health; Randomized; Randomized Controlled Trials; Relapse; Research; Risk; Role; Sertraline; Site; Weight; Weight Gain; age effect; atypical antipsychotic; clinically relevant; clinically significant; evidence base; innovation; meetings; mortality; olanzapine; older patient; open label; premature; prevent; psychotic depression; randomized placebo controlled trial; response; young adult; Acute; Address; Adverse effects; Age; Antidepressive Agents; Antipsychotic Agents; Benefits and Risks; Cholesterol; Clinical; Collaborations; Combined Modality Therapy; Disease; Disease remission; Double-Blind Method; Drug Kinetics; Elderly; Electroconvulsive Therapy; Exposure to; Funding; Genetic Polymorphism; Goals; Guidelines; Hypertriglyceridemia; Impaired cognition; Inpatients; Leadership; Lipids; Major Depressive Disorder; Mental Depression; Mental disorders; Metabolic; Morbidity - disease rate; National Institute of Mental Health; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Placebos; Population; Prevalence; Principal Investigator; Public Health; Randomized; Randomized Controlled Trials; Relapse; Research; Risk; Role; Sertraline; Site; Weight; Weight Gain; age effect; atypical antipsychotic; clinically relevant; clinically significant; evidence base; innovation; meetings; mortality; olanzapine; older patient; open label; premature; prevent; psychotic depression; randomized placebo controlled trial; response; young adult

DESCRIPTION (provided by applicant): Psychotic depression (PD) is a severe disabling disorder with considerable morbidity and mortality. Between 19% and 45% of inpatients with major depression have psychotic features, with greater prevalence in older patients. Although electroconvulsive therapy has well-established efficacy in the treatment of PD, its use is limited by several factors. As a result, the pharmacologic treatment of PD is common. Expert guidelines recommend the combination of antidepressant and antipsychotic medications in the pharmacologic treatment of PD. The recently completed Study of the Pharmacotherapy of Psychotic Depression (STOP-PD) was the first NIMH-funded randomized controlled trial (RCT) to examine the efficacy and tolerability of newer antidepressant and antipsychotic medications in the acute treatment of younger and older persons with PD. The combination of sertraline and olanzapine was significantly more efficacious than olanzapine combined with placebo. Both treatments were equally well tolerated, but were associated with clinically significant weight gain and elevation of lipids. Older persons, however, had significantly less weight gain than younger persons. Little is known about the continuation treatment of PD. Of particular concern, it is not known whether antipsychotic medication needs to be continued once an episode of PD responds to pharmacotherapy. This issue has profound clinical relevance. On the one hand, the unnecessary continuation of antipsychotic medication exposes a patient to adverse effects, such as weight gain and metabolic disturbance. On the other hand, premature discontinuation of antipsychotic medication has the potential risk of early relapse of a severe disorder. The primary goal of this Renewal application, therefore, is to assess the risks versus benefits of continuing olanzapine in younger and older patients with PD, once the episode of depression has responded to treatment with sertraline and olanzapine. This goal will be addressed through a 36-week double-blind RCT, in which placebo is substituted for olanzapine in half the study group, following a period of sustained remission. We hypothesize that sertraline+olanzapine will be more efficacious than sertraline+placebo in preventing relapse of PD. This study provides the unique opportunity to systematically assess the effect of antipsychotic discontinuation (as opposed to switching from one antipsychotic to another) on olanzapine-related weight gain and metabolic disturbance. Additional innovative aims of the study are to examine age and genetic polymorphisms as predictors/moderators of treatment variability, potentially leading to more personalized treatment of PD, and to employ population pharmacokinetics to determine the magnitude and consistency of exposure to study drugs. Olanzapine is selected because it is the only atypical antipsychotic with established efficacy and tolerability in the treatment of both younger and older adults with PD . This research will be transformative, by providing clinicians with a much-needed evidence base to guide the continuation treatment of one of the most disabling and lethal psychiatric disorders.

描述（由申请人提供）：精神病抑郁症（PD）是一种严重的残疾疾病，具有相当大的发病率和死亡率。患有严重抑郁症的住院患者的19％至45％具有精神病特征，老年患者患病率更高。尽管电击疗法在PD的治疗方面具有良好的功效，但其使用受到多种因素的限制。结果，PD的药理治疗很常见。专家指南建议将抗抑郁药和抗精神病药物结合在PD的药理学治疗中。最近完成的对精神病抑郁症药物治疗（Stop-PD）的研究是NIMH资助的随机对照试验（RCT），用于检查新抗抑郁药和抗精神病药在急性治疗PD的急性治疗中的疗效和耐受性。舍曲林和奥氮平的结合比奥氮平的结合与安慰剂相结合。两种治疗方法均具有良好的耐受性，但与临床上显着的体重增加和脂质升高有关。但是，老年人的体重增加明显少于年轻人。关于PD的持续处理知之甚少。特别令人担忧的是，一旦PD发作对药物治疗做出反应，是否需要继续进行抗精神病药。这个问题具有深远的临床意义。一方面，抗精神病药的不必要延续使患者暴露于不良反应，例如体重增加和代谢障碍。另一方面，抗精神病药物的过早停用具有严重疾病早期复发的潜在风险。因此，该更新应用的主要目的是评估抑郁症的发作对舍曲雷林和奥氮平的治疗做出反应，在年轻和老年患者中继续使用奥氮平的风险与益处。该目标将通过一个36周的双盲RCT来解决，在持续缓解后，安慰剂在研究组的一半中代替奥氮平。我们假设舍曲林+奥氮平比舍曲林+安慰剂在防止PD复发方面更有效。这项研究提供了独特的机会，可以系统地评估抗精神病药停药的影响（与从一种抗精神病药转换为另一种抗精神病药）对奥氮平相关的体重增加和代谢障碍的影响。该研究的其他创新目的是研究年龄和遗传多态性，作为治疗变异性的预测因子/主持人，可能导致对PD的更个性化的治疗，并使用人群药代动力学来确定研究药物的暴露程度和一致性。之所以选择奥氮平是因为它是唯一的非典型抗精神病药，在治疗PD的年轻和老年人方面具有既定功效和耐受性。通过为临床医生提供急需的证据基础，以指导对最残疾和致命的精神疾病之一的继续治疗，这项研究将具有变革性。