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。与非精神病性抑郁症相比，PD与更严重的抑郁程度、功能障碍和抗抑郁治疗的耐药性相关。从纵向上看，PD与更大的复发可能性、更短的无症状间隔、更大的残疾和增加的长期自杀风险相关。在老年患者中，PD也与高的一年死亡率相关。虽然电痉挛疗法（ECT）是一种非常有效的PD治疗方法，但药物治疗更容易实施，并且通常被许多患者和精神科医生首选。此外，少数民族、低收入患者和居住在农村地区的患者较少使用ECT，而且使用频率也较低。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，高剂量叔胺三环和常规抗精神病药物的联合使用比单独使用任何一种药物更有效。然而，这种组合与严重副作用的高发有关，特别是在老年患者中。

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.