Prophylactic Cognitive Therapy for Depression

描述（由申请人提供）：在本竞争性续期申请中，我们要求提供五年的资金，以完成第一项充分把握度的安慰剂（PBO）对照随机临床试验，评价持续阶段认知治疗（C-CT）和氟西汀（FLX）在复发高危复发性重度抑郁症（MDD）门诊患者中的疗效。该试验正在德克萨斯大学西南医学中心和匹兹堡大学医学院进行。“高风险”定义为急性期CT最后几周的不完全缓解，而“低风险”定义为完全和稳定的缓解。这项试验具有重大的公共卫生意义，因为它将帮助临床医生确定那些复发风险最大的患者，这些患者需要更长的治疗疗程。这种基于诊断的决策规则可以通过为抑郁发作提供足够的治疗来降低护理成本，而不会对低风险患者进行“过度治疗”或对高风险患者进行“治疗不足”。这项研究是第一个评估急性期CT不完全缓解后的继续阶段药物治疗（FLX）。此外，药物治疗组将允许测试模式特异性与非特异性治疗活性。因变量测量响应、复发、再发、缓解和恢复。计划进行盲法评价和生存分析。在本次竞争性更新的第6 - 9年，共将入组288例新患者（总计n=724）。根据计划（设盲）中期分析的结果，本研究将继续作为三组试验（每组105例患者）完成，或将受试者从第6年开始转移至两个活性治疗组（每组129例患者）。这一修改是为了最大限度地提高C-CT和FLX治疗比较的统计学功效，而不影响C-CT与PBO的试验有效性。根据迄今为止取得的结果（即，C-CT 8%复发，PBO估计约24%复发），中期分析将确定是否需要更多受试者来回答主要问题（即，C-CT与对照），或者是否可以将工作转移到比较FLX相对于C-CT的相对优点。具体而言，如果在“阶段1”结束时C-CT比PBO显著更有效，则FLX必须也具有治疗活性。

DESCRIPTION (provided by applicant): In this application for competing renewal, we request funding for five years to complete the first adequately powered, placebo (PBO) controlled randomized clinical trial evaluating the efficacy of continuation phase cognitive therapy (C-CT) and fluoxetine (FLX) in outpatients with recurrent Major Depressive Disorder (MDD) who are at high risk for relapse. The trial is being conducted at The University of Texas Southwestern Medical Center and The University of Pittsburgh School of Medicine. "Higher risk" is defined by incomplete remission during the final weeks of acute phase CT, while "lower risk" is defined as a complete and stable remission. This trial has great public health significance because it will help clinicians to identify those patients at greatest risk for relapse who warrant longer courses of treatment. Such empirically-based decision rules could lower the cost of care by providing enough treatment for a depressive episode without either "over-treating" patients at lower risk or "under-treating" those patients at higher risk. This study is the first to evaluate continuation phase pharmacotherapy (FLX) after incomplete remission with acute phase CT. Further, the pharmacotherapy group will permit tests of mode-specific vs. non-specific therapeutic activity. Dependent variables measure response, relapse, recurrence, remission, and recovery. Blind evaluations and survival analyses are planned. A total of 288 new patients will be enrolled in years 06-09 of this competing renewal (Total n=724). Based on results of a planned (blinded) interim analysis, the study will either continue to completion as a three-arm trial (105 patients per arm) or will shift allocation of subjects from year 06 onward into the two active treatment arms (129 patients per arm). This modification has been made to maximize the statistical power for comparisons of C-CT and FLX therapies, without undermining the test efficacy of C-CT versus PBO. Based on results obtained to date (i.e., C-CT 8% relapse, PBO estimate approximately 24% relapse), the interim analysis will determine if more subjects are needed to answer the primary question (i.e., C-CT versus control) or if efforts can be shifted to comparing the relative merits of FLX relative to C-CT. Specifically, if C-CT is significantly more effective than PBO at the end of "Phase 1," then FLX must also have therapeutic activity.