Prophylactic Cognitive Therapy for Depression

描述（由申请人提供）：在此竞争性续期申请中，我们要求资助五年，以完成第一个充分有效的安慰剂（PBO）对照随机临床试验，评估持续期认知疗法（C-CT）和氟西汀（FLX）对复发性重度抑郁症（MDD）门诊患者的疗效，这些患者复发的风险很高。这项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最后几周不完全缓解，而“低风险”定义为完全稳定缓解。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、需要更长疗程的患者。这种基于经验的决策规则可以通过为抑郁症发作提供足够的治疗来降低护理成本，既不会“过度治疗”风险较低的患者，也不会“治疗不足”风险较高的患者。该研究首次评估急性期CT不完全缓解后的持续期药物治疗（FLX）。此外，药物治疗组将允许对模式特异性和非特异性治疗活性进行测试。因变量衡量反应、复发、复发、缓解和恢复。计划进行盲评价和生存分析。在这一竞争性更新的06-09年，共有288名新患者入组（总n=724）。根据计划（盲法）中期分析的结果，该研究将继续作为三组试验（每组105例患者）完成，或者将受试者分配从第06年转移到两个积极治疗组（每组129例患者）。这一修改是为了最大限度地提高C-CT和FLX治疗比较的统计能力，而不会破坏C-CT与PBO的测试效果。根据迄今为止获得的结果（即C-CT复发率为8%，PBO估计复发率约为24%），中期分析将确定是否需要更多的受试者来回答主要问题（即C-CT与对照组），或者是否可以将努力转移到比较FLX相对于C-CT的相对优点上。具体来说，如果C-CT在“1期”结束时明显比PBO更有效，那么FLX也必须具有治疗活性。

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.