Acute Pharmacotherapy of Unipolar Psychotic Depression

描述（由申请人提供）：精神病性抑郁症（PD）是一种严重的疾病，存在于20%的混合年龄住院患者和超过40%的老年住院患者中，用于治疗重度抑郁症。在急性期，PD比非精神病性抑郁症与更高水平的抑郁症严重程度、功能损害和抗抑郁治疗抵抗相关。纵向上，PD与更大的复发可能性、更短的无复发间期、更大的残疾和更高的长期自杀风险相关。在老年患者中，PD也与高1年死亡率相关。虽然电休克治疗（ECT）是一种非常有效的治疗PD，药物治疗更容易管理，通常是许多患者和精神科医生的首选。此外，少数民族群体、低收入患者和居住在农村地区的患者较少使用ECT。在20世纪80年代早期，一项具有里程碑意义的NIMH随机对照试验表明，高剂量的叔胺三环和常规抗精神病药的组合比任何一种药物的单一治疗更有效。然而，这种组合与显著副作用的高发生率相关，特别是在老年患者中。 这个合作U01项目建立在四个地点的主要研究者和其他人的研究结果的基础上。基于初步研究表明舍曲林（一种SSRI）和奥氮平（一种非典型抗精神病药）可能对PD的急性治疗有效，本研究采用双臂随机双盲平行组设计，比较这两种药物联合治疗与奥氮平单药治疗的疗效和耐受性。通过以1：1的比例阻断招募年龄大于或等于60岁的受试者，研究将确定年龄较大与缓解、至缓解时间和耐受性之间的关系。为期12周的急性期疗效研究之后是为期20周的延续试验，在此期间，达到部分缓解的受试者进入基于其初始分配的安慰剂对照增强试验。在稳定期间还对缓解受试者进行随访，以确定缓解的稳定性以及临床和功能恶化的预测因子。

DESCRIPTION (provided by applicant): Psychotic depression (PD) is a severe disorder that is present in 20% of mixed-age inpatients and in more than 40% of elderly inpatients hospitalized for the treatment of major depression. Acutely, PD is associated with a greater level of depression severity, functional impairment, and resistance to antidepressant treatment than nonpsychotic depression. Longitudinally, PD is associated with a greater likelihood of recurrence, a shorter symptom-free interval, greater disability, and an increased long-term risk of suicide. Among elderly patients, PD has also been associated with a high one year mortality rate. Although electroconvulsive therapy (ECT) is a highly effective treatment for PD, pharmacotherapy is more easily administered and generally preferred by many patients and psychiatrists. Furthermore, ECT is less available to, and less frequently used by minority ethnic groups, patients with low incomes, and those residing in rural areas. In the early 1980's a landmark NIMH randomized controlled trial demonstrated that a combination of high doses of both a tertiary amine tricyclic and a conventional antipsychotic was more efficacious than monotherapy with either medication. However, this combination has been associated with a high incidence of significant side effects, particularly in elderly patients. This collaborative U01 project builds on findings from the four sites principal investigators and others. Based on preliminary studies suggesting that sertraline, a serotonin-reuptake-inhibitor (SSRI) and olanzapine, an atypical antipsychotic, may be effective in the acute treatment of PD, this study uses a two-armed randomized double-blind parallel-group design to compare the efficacay and tolerability of combining these two medications to olanzapine alone. By blocking recruitment of subjects age greater than or equal to 60 on a 1:1 basis the study will determine the relationship between older age and remission, time to remission and tolerability. A 12-week acute phase efficacy study is followed by a 20-week continuation trial during which subjects who achieved partial remission enter a placebo-controlled augmentation trial that is based on their initial assignment. Remitted subjects are also followed during stabilization to determine the stability of remission and predictors of clinical and functional deterioration.