Divalproex and Placebo, Lithium, or Quetiapine for Mania

描述（由申请人提供）：在过去五年中，用于治疗双相情感障碍患者的新药物选择有所扩展。虽然单药治疗研究是为了获得FDA对新药的批准，但很少有联合治疗研究已经完成，特别是超过三周的急性期。尽管缺乏证据，但联合治疗已成为常见的临床实践，如多项调查和出版物所反映的。我们提出了一个随机，安慰剂对照研究双丙戊酸钠（DVP）加盲安慰剂（PBO），碳酸锂（Li），或奎替鲁胺（QTP）在105例患者目前轻躁狂超过12周的急性期。 我们假设在急性期12周试验中，联合治疗（DVP+Li和DVP+QTP）与单药治疗（DVP+PBO）相比，轻躁狂和躁狂症状的减轻程度更大。所有入组的患者都将符合双相I型障碍的标准，并至少经历中度轻躁狂。第12周时符合恢复标准的患者将继续接受14周DVP加设盲药物（PBO、Li或QTP）治疗。该阶段将提供关于初始治疗组合的应答者的特征和病程的探索性数据。研究中纳入了许多程序，以确保患者保护。一个盲态的精神病学家和研究助理将在四周内每周一次看望病人，然后在他们参与的期间每两周一次。一位非盲态精神科医生将监测症状、实验室检查结果和血清水平。症状测量将包括杨氏躁狂评定量表、汉密尔顿抑郁评定量表、双相情感障碍临床总体评估以及其他生活质量、功能和身体症状和副作用的测量。 本研究将提供关于最合适的初始治疗策略的基本信息和关于继续治疗的初步证据。我们计划使用三组之间的斜率（响应率）测试对主要目的（表现症状的变化）进行随机回归分析。次要目标集中在抑郁症状和副作用。使用调节者和中介者方法的探索性分析将寻求这些治疗对谁最有帮助以及研究设计中的关键要素是什么的信息，以提高未来双相情感障碍治疗研究的效应量。

DESCRIPTION (provided by applicant): There has been an expansion of new medication options for the treatment of patients with bipolar disorder in the last five years. While monotherapy studies are done to win FDA approval of a new drug, few combination studies have been completed, particularly extending beyond a three-week acute period. Despite the lack of evidence combination therapy has become usual clinical practice, as reflected in multiple surveys and publications. We propose a randomized, placebo-controlled study of divalproex (DVP) plus blinded placebo (PBO), lithium carbonate (Li), or quetiapine (QTP) in 105 patients currently hypomanic over a 12-week acute period. We hypothesize the combination treatments (DVP+Li and DVP+QTP) will be associated with greater reduction in symptoms of hypomania and mania than monotherapy alone (DVP+PBO) durng the acute phase 12-week trial. All patients entering will meet criteria for bipolar I disorder and be experiencing at least moderate hypomania. Patients meeting criteria for recovery at 12 weeks will be offered a 14-week continuation on DVP plus blinded medication (PBO, Li, or QTP). This phase will provide exploratory data on the characteristics and course of responders to the initial treatment combinations. Many procedures are incorporated into the study to ensure patient protection. A blinded psychiatrist and research assistant will see patients at weekly intervals for four weeks, and then every two weeks for the duration of their involvement. An unblinded psychiatrist will monitor symptoms, laboratory results, and serum levels. Symptom measures will include the Young Mania Rating Scale, Hamilton Rating Scale for Depression, Clinical Global Assessment for Bipolar Disorder, and other measures of quality of life, functioning, and physical symptoms and side effects. This study will provide fundamental information on the most appropriate initial treatment strategy and preliminary evidence on continuation treatment. We plan a random regression analysis of the primary aim of change of presenting symptoms using a test of slopes (response rates) among the three groups. Secondary aims focus on depressive symptoms and side effects. An exploratory analysis using the Moderator and Mediator approach will seek information on whom these treatments will be most helpful for and what are critical elements within the study design to enhance effect size in future studies on treatment of bipolar disorder.