Improving Depression Treatment Outcomes with an Insulin-Sensitizing Agent

使用胰岛素增敏剂改善抑郁症治疗效果

• 批准号: 8067099
• 负责人: PATRICK J LUSTMAN
• 金额: $ 62.78万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-10 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8067099
• 关键词: Abate; Acute; Affect; Amputation; Anthropometry; Antidepressive Agents; Blindness; Body Composition; Cardiovascular Diseases; Cause of Death; Clinical; Clinical Treatment; Complications of Diabetes Mellitus; Cox Proportional Hazards Models; Depressed mood; Diabetes Mellitus; End stage renal failure; Epidemic; Ethics; Exposure to; Goals; Healthcare; Homeostasis; Hydrocortisone; Hyperglycemia; Individual; Insulin; Insulin Resistance; Limb structure; Maintenance; Major Depressive Disorder; Measures; Mental Depression; Metformin; Modeling; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Outcome; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physical activity; Placebos; Population; Prevalence; Prevention; Public Health; Quality of life; Randomized; Randomized Clinical Trials; Recovery; Recurrence; Research; Risk; Sampling; Sertraline; Severities; Testing; Time; Treatment outcome; depressive symptoms; diet and exercise; double-blind placebo controlled trial; glycemic control; heuristics; improved; insulin sensitivity; insulin sensitizing drugs; lifetime risk; meetings; mortality; novel; response; rosiglitazone; treatment adherence; treatment effect; treatment strategy

DESCRIPTION (provided by applicant): Depression affects 1 in 4 individuals with type 2 diabetes, the principal manifestation of insulin resistance (IR), and is associated with hyperglycemia, diabetes complications, and mortality. Glycemic control improves significantly with depression treatment, and the gains are sustained throughout the subsequent depression- free interval. However, current depression treatment strategies fail to induce recovery in one-half of these patients and permit recurrence in one-third within a year. Several lines of evidence indicate that IR (depression-related or depression-independent) interferes with response to depression treatment and maintenance of the depression-free state. Therefore, we propose a two-phase (acute, 16 weeks; maintenance, 24 weeks), randomized, double-blind, placebo-controlled trial of treatment for major depressive disorder (MDD) in persons with IR, testing the following hypothesis: reduction in depression symptoms is greater (acute phase) and recurrence of depression is delayed (maintenance phase) in patients receiving insulin sensitizer augmentation of conventional antidepressant pharmacotherapy compared to patients treated with conventional pharmacotherapy alone. 200 subjects with MDD and IR [BMI >28.7 kg/m2 and homeostasis model of insulin resistance (HOMA-IR) >3.6] receive sertraline (SRT) and additional randomly assigned treatment with rosiglitazone (ROS) or placebo (PBO). For practical and ethical reasons, only patients with IR and without overt diabetes will be included. Those meeting criteria for MOD recovery will continue treatment for an additional 6 months while nonrecovered subjects will be referred for out-of- study depression management. Measures of depression, IR (from OGTT minimal model), glycemia, anthropometries, treatment adherence, physical activity and quality of life will be taken at baseline (pre- treatment) and the point of depression recovery/nonrecovery. In the recovered subset, additional measures will be taken at the time of MDD recurrence or 6 months after recovery in those remaining depression free. The primary endpoints are the reduction in depression symptom severity during the acute phase and elapsed time-to-recurrence (TTR) of MDD during the maintenance phase. Multiple regression (acute phase) and Cox proportional hazards models (maintenance phase) will be used to determine treatment effects as well as independent predictors of depression improvement and TTR. The principal hypotheses are that reduction in depression is greater and TTR is significantly longer in patients treated with SRT+ROS compared to those receiving SRT+PBO, and that reduction in IR independently predicts these favorable outcomes. If the hypotheses are supported, the study would have far-reaching scientific and public health implications: It will identify a novel treatment and a new treatment target for enhancing responsiveness to antidepressant therapy and lengthening the subsequent depression-free interval in patients with IR (With or without diabetes). The findings would represent a significant advance in depression treatment.

描述（由申请人提供）：抑郁症会影响4分之一的2型糖尿病患者，胰岛素抵抗（IR）的主要表现，并且与高血糖，糖尿病并发症和死亡率有关。通过抑郁治疗，血糖控制可显着改善，并且在随后的抑郁间隔内持续增长。但是，当前的抑郁症治疗策略无法诱导这些患者的一半恢复，并且在一年内允许三分之一复发。几条证据表明，IR（与抑郁症无关或与抑郁症无关）会干扰抑郁症治疗和无抑郁状态的响应。因此，我们提出了两相（急性，16周；维持，24周），随机，双盲，安慰剂控制的重度抑郁症治疗试验（MDD）在患有IR的患者中，测试以下假设：抑郁症状的减少：抑郁症的抑郁症的抑郁症较大（急性相结合）在抑郁症中的延迟（急性渗透率）是延迟的（维持胰岛素的复发）。单独接受常规药物治疗的患者。 200名MDD和IR [BMI> 28.7 kg/m2的受试者以及胰岛素耐药性（HOMA-IR）> 3.6]接受舍曲林（SRT）和其他随机分配的治疗方法（ROSIGLITAZONE（ROS）（ROS）或安慰剂（PBO）。出于实际和道德原因，只有IR和没有明显糖尿病的患者才能包括在内。那些满足国防部恢复标准的人将继续治疗6个月，而未被批准的受试者将被转移到研究外抑郁管理中。抑郁症的度量，IR（来自OGTT最小模型），血糖，拟人化，治疗依从性，体育活动和生活质量将在基线（前治疗）以及抑郁症的恢复/不恢复点时采取。在回收的子集中，将在MDD复发时采取其他措施，或者在恢复抑郁症的人恢复后6个月后将采取其他措施。主要终点是急性阶段抑郁症状严重程度的降低，并在维护阶段经过MDD的时间次数（TTR）。多重回归（急性期）和COX比例危害模型（维持阶段）将用于确定治疗效果以及抑郁改善和TTR的独立预测指标。主要假设是，与接受SRT+PBO的患者相比，用SRT+ROS治疗的患者的抑郁症减少更大，TTR明显更长，而IR的减少则独立预测这些有利的结果。如果支持假设，该研究将具有深远的科学和公共卫生影响：它将确定一种新的治疗方法和新的治疗范围，以增强对抗抑郁药治疗的反应性并延长IR患者（或患有糖尿病患者）的随后无抑郁间隔。这些发现将代表抑郁症治疗的重大进展。