Treatment for Bipolar Depression: Acute & Prophylactic Efficacy with Citalopram

描述（由申请人提供）：本提案是NIMH MH-0708060-01新申请的首次重新提交，该申请要求5年的资助，题为“治疗双相抑郁症：西酞普兰的急性和预防性疗效”。要检验的主要假设与一项随机临床试验有关，研究抗抑郁药对双相抑郁症的疗效。申请人将研究将血清素再摄取抑制剂（SRI）西酞普兰添加到标准情绪稳定剂中，以双盲、安慰剂对照、随机方式进行6周急性疗效和1年维持疗效的影响。此外，该应用程序旨在通过基因组学和功能神经影像学的测量获得双相情感障碍抑郁症病理生理学的新知识，并首次获得治疗反应的生物学预测以及抗抑郁药（如躁狂症）的不良后果。该提案是在完成了对双相情感障碍长期抗抑郁疗效的主要研究者的R23奖之后提出的。理由：与单极重性抑郁症相比，双相抑郁症是研究最少的抑郁症之一，很少有关于抗抑郁药与情绪稳定剂联合使用的短期和长期疗效或安全性的研究，或者它们对双相情感障碍病程的影响。先前的研究已经确定了持续使用抗抑郁药治疗双相情感障碍可能存在的风险，包括诱发躁狂症、混合状态、精神病或快速循环。尽管存在这些潜在的风险，双相情感障碍的抑郁期在临床上是足够引人注目的，抗抑郁药而不是情绪稳定剂是双相情感障碍最常用的治疗方法，支持本建议的时效性。目前尚不清楚这些抗抑郁治疗在这种情况下是否有效，甚至是否安全。此外，虽然在单极抑郁症中已经研究了抗抑郁药物反应的功能神经影像学和遗传预测因素，但在双相抑郁症中，类似的机制在很大程度上是未知的。公共卫生影响：双相抑郁症是一种致命的情绪障碍，具有高自杀率和显著的工作和社会生产力损失。抗抑郁药被广泛使用，因此有必要知道它们是否应该被广泛使用，或者它们的使用是否应该受到更多限制；然而，关于它们在双相抑郁症中的有效性和安全性，几乎没有严谨的科学证据。特别是考虑到一些患者服用抗抑郁药可能会明显恶化，更好地了解何时使用抗抑郁药，何时不使用，双相情感障碍患者的抗抑郁药是一个主要的公共卫生问题。

DESCRIPTION (provided by applicant): This proposal represents the first resubmission of the new application NIMH MH-0708060-01, which requests 5 years of funding for the grant entitled "Treatment for Bipolar Depression: Acute & Prophylactic Efficacy with Citalopram." The primary hypothesis to be tested relates to a randomized clinical trial into antidepressant efficacy in bipolar depression. The applicant will study the impact of a serotonin reuptake inhibitor (SRI), citalopram, added to standard mood stabilizers in a double-blind, placebo- controlled, randomized fashion for 6 week acute efficacy, along with 1 year maintenance efficacy. In addition, the application seeks to acquire novel knowledge about the pathophysiology of depression in bipolar disorder using measures of genomics and functional neuroimaging, and, for the first time, biological predictors of treatment response as well as adverse outcomes with antidepressants (such as mania). The proposal follows up on completion of a R23 award to the principal investigator on long-term antidepressant outcome in bipolar disorder. Rationale: In contrast to unipolar major depression, bipolar depression is among the least studied depressive illnesses, with very little research on the short- and long-term efficacy or safety of antidepressants used in conjunction with mood-stabilizing agents, or their effect on the course of bipolar disorder. Previous studies have identified possible risks of sustained treatment with antidepressants in bipolar disorder, including induction of mania, mixed states, psychosis, or rapid-cycling. Despite these potential risks, the depressive phase of bipolar disorder is sufficiently compelling clinically that antidepressants rather than mood-stabilizing agents are the most commonly used treatments in bipolar disorder, supporting the timeliness of the present proposal. It is unknown if these antidepressant treatments are effective or even safe in these circumstances. Further, while functional neuroimaging and genetic predictors of response with antidepressants have been studied in unipolar depression, similar mechanisms in bipolar depression are largely unknown. Public Health Implications: Bipolar depression is a virulent mood disorder, with a high suicide rate and marked loss of work and social productivity. Antidepressants are commonly used, making it essential to know if they should be used extensively as they are, or whether their use should be more restricted; yet there is little to no rigorous scientific evidence regarding their efficacy and safety in bipolar depression. Especially given suggestions that some patients may markedly worsen with antidepressants, better understanding of when to use, and when not to use, antidepressants in bipolar disorder is a major public health concern.