Randomized trial of sertraline treatment of depression in Chronic Kidney Disease

描述（由申请人提供）： 抑郁症是慢性肾脏病（CKD）慢性透析患者的常见合并症，也是住院和死亡的独立风险因素。我们的初步数据显示，21%患有透析前CKD的退伍军人患有重度抑郁发作（MDE），并且与合并症无关，与没有MDE的人相比，患有MDE的人在一年内住院，开始透析或死亡的可能性高出2倍。然而，只有少数患有抑郁症的CKD患者接受抗抑郁药治疗。治疗率低的原因包括缺乏明确支持或反驳抗抑郁药在CKD患者中的疗效和安全性的已发表数据。舍曲林抗抑郁剂心脏病发作随机试验显示舍曲林对心血管结局有益，但排除了中度至重度CKD患者。鉴于CKD患者心血管（CV）死亡率过高以及抑郁症与CV事件增加的相关性，不仅必须研究抑郁症治疗在这些患者中是否安全有效，而且还必须研究抑郁症治疗是否会导致CV死亡率降低。此外，先前的研究表明，部署压力源和暴露于战斗导致相当大的心理健康问题的风险，如严重抑郁症，特别是在退伍军人中，这导致社会功能和工作能力的损害。心理健康问题也导致增加利用医疗保健服务，因此，医疗保健相关的费用退伍军人。我们假设舍曲林短期治疗MDE可改善透析前3-5期CKD患者的抑郁症状严重程度和生活质量。我们进一步假设，在这些患者中，舍曲林治疗MDE不会导致比安慰剂治疗更严重的不良事件。本研究的具体目的是：1）在一项随机、双盲、安慰剂对照、灵活剂量、为期12周的试验中，确定舍曲林治疗与安慰剂治疗相比是否能改善抑郁症状的严重程度，该试验涉及200名患有透析前3-5期CKD的退伍军人; 2）确定舍曲林治疗是否改善了整体功能和生活质量，分别通过工作和社会适应量表和简表12评分进行评估;和3）确定舍曲林与安慰剂相比是否会导致更严重的不良事件，包括需要输血或住院的出血。现成的患者人群和我们经验证的测量抑郁症的方法学的应用是一个强大的组合，将有助于提供关于典型SSRI在CKD患者中的疗效和安全性的急需数据。这些数据可用于支持未来的多中心大规模试验，旨在确定抑郁症治疗是否改善CKD患者的发病率，死亡率和生活质量。 公共卫生相关性： 与退伍军人健康的相关性是提供关于慢性肾病患者中典型的阿托伐他汀选择性再摄取抑制剂的有效性和安全性的迫切需要的数据，这些数据可用于为未来的多中心大规模试验提供动力，例如退伍军人事务合作研究，旨在确定抑郁症的治疗是否改善发病率，死亡率和生活质量，以及减少医疗保健服务的利用，在这些患者中。这对退伍军人患者人群尤为重要，因为他们的抑郁症和慢性肾脏病等医学共病的患病率较高。

DESCRIPTION (provided by applicant): Depression is a common co-morbidity and an independent risk factor for hospitalization and death in Chronic Kidney Disease (CKD) patients on chronic dialysis. Our preliminary data revealed that 21% of Veterans with predialysis CKD suffer from a major depressive episode (MDE) and that, independent of co-morbidities, those with a MDE are 2 times more likely to be hospitalized, initiate dialysis or die within a year as compared to those without a MDE. However, only a minority of CKD patients with depression are treated with antidepressants. Reasons for low treatment rates include a lack of published data that clearly support or refute efficacy and safety of antidepressants in CKD patients. The Sertraline AntiDepressant Heart Attack Randomized Trial showed benefit of serotonin-selective reuptake inhibitor (SSRI) sertraline on cardiovascular outcomes but excluded patients with moderate to severe CKD. Given the excessive rates of cardiovascular (CV) death in CKD patients and the correlation of depression with increased CV events, it becomes imperative to not only investigate whether treatment of depression is safe and efficacious in these patients, but also whether it would result in a reduction in CV mortality. In addition, prior research has shown that deployment stressors and exposure to combat result in considerable risks of mental health problems such as major depression particularly in Veterans, which results in impairment in social functioning and in the ability to work. Mental health problems also lead to increased utilization of health care services and, therefore, health care-related costs among Veterans. We hypothesize that short-term treatment of a MDE with sertraline will improve depression symptom severity and quality of life in patients with predialysis stages 3-5 CKD. We further hypothesize that treatment of MDE with sertraline will not result in more serious adverse events than treatment with placebo in these patients. The specific objectives of this study are to 1) determine if treatment with sertraline, as compared with placebo, results in an improvement in depression symptom severity in a randomized, double-blinded, placebo-controlled flexible-dose 12-week trial involving 200 Veterans with predialysis stages 3-5 CKD; 2) determine if sertraline treatment improves overall function and quality of life as assessed by the Work and Social Adjustment Scale and the Short Form 12 scores, respectively; and 3) determine if sertraline, as compared with placebo, will result in more serious adverse events including bleeding requiring blood transfusion or hospitalization. The readily available patient population and the application of our proven methodology for measuring depression is a powerful combination that will help provide urgently needed data on the efficacy and safety of a typical SSRI in CKD patients. These data can be used to power a future multi-center large-scale trial designed to determine whether treatment of depression improves morbidity, mortality and quality of life in patients with CKD. PUBLIC HEALTH RELEVANCE: The relevance to Veteran's health is providing urgently needed data on the efficacy and safety of a typical serotonin-selective reuptake inhibitor in Chronic Kidney Disease patients that can be used to power a future multi-center large-scale trial, such as a Veterans Affairs Cooperative Study, designed to determine whether treatment of depression improves morbidity, mortality and quality of life, as well as lessens health care services utilization, in these patients. This becomes particularly important to the Veteran patient population that has a higher prevalence of both depression and medical co-morbidities such as Chronic Kidney Disease.