Divalproex and Placebo, Lithium, or Quetiapine for Mania

描述(由申请人提供)：在过去的五年中，双相情感障碍患者的治疗有了新的药物选择的扩展。虽然单一疗法研究是为了获得FDA对新药的批准，但很少有联合研究完成，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那样。我们提出了一项随机、安慰剂对照研究，对105名目前躁狂症状较低的患者进行为期12周的急性期异丙丙胺(DVP)加盲用安慰剂(PBO)、碳酸锂(Li)或奎硫平(QTP)的研究。 我们推测，在为期12周的急性期试验中，联合治疗(DVP+LI和DVP+QTP)与单一治疗(DVP+PBO)相比，将更大程度地减轻轻躁狂和躁狂症状。所有进入的患者都将符合双相I型障碍的标准，并至少经历中度的轻躁狂。符合12周恢复标准的患者将接受14周的DVP加盲药(PBO、LI或QTP)的治疗。这一阶段将提供有关初始治疗组合应答者的特征和疗程的探索性数据。许多程序被纳入研究中，以确保患者的保护。一位失明的精神病学家和研究助理将在四周内每周一次为患者看病，然后在他们参与治疗的过程中每两周一次。一位非盲目的精神病学家将监测症状、实验室结果和血清水平。症状测量将包括青年躁狂评定量表、汉密尔顿抑郁量表、双相情感障碍临床全球评估，以及其他生活质量、功能、身体症状和副作用的测量。 这项研究将为最合适的初始治疗策略提供基本信息，并为继续治疗提供初步证据。我们计划通过对三组患者的斜率(反应率)的测试，对改变症状的主要目的进行随机回归分析。次要目标是关注抑郁症状和副作用。使用调解人和调解人方法的探索性分析将寻求关于这些治疗对谁最有帮助的信息，以及研究设计中的关键因素是什么，以在未来的双相情感障碍治疗研究中提高效果大小。

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.