Prophylactic Cognitive Therapy for Depression

描述(申请人提供)：在这份竞争性续签申请中，我们申请为期五年的资金，以完成第一项充分有效的安慰剂(PBO)对照随机临床试验，评估持续阶段认知疗法(C-CT)和氟西汀(Floxetine)对复发风险高的重度抑郁障碍(MDD)门诊患者的疗效。该试验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”被定义为在急性期CT的最后几周不完全缓解，而“低风险”被定义为完全稳定的缓解。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哪些患者的复发风险最高，需要进行更长的疗程。这种基于经验的决策规则可以降低护理成本，因为它可以为抑郁发作提供足够的治疗，而不会对风险较低的患者进行过度治疗，也不会对风险较高的患者进行治疗不足。这项研究是首次通过急性期CT评估不完全缓解后继续期药物治疗(FLX)的效果。此外，药物治疗组将允许对特定模式与非特定治疗活动进行测试。因变量衡量反应、复发、复发、缓解和恢复。计划进行盲目评估和生存分析。在这一竞争更新的06-09年间，总共将有288名新患者入选(总计724名)。根据计划(盲法)中期分析的结果，这项研究将继续作为三组试验(每组105名患者)完成，或者将从06年起将受试者分配到两个积极的治疗组(每组129名患者)。这一修改是为了最大限度地提高C-CT和FLX疗法比较的统计能力，而不会破坏C-CT与PBO的测试效果。根据到目前为止获得的结果(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)，或者是否可以将精力转移到比较Flx相对于C-CT的相对优点。具体地说，如果C-CT在“第一阶段”结束时明显比PBO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.