Treatment for Bipolar Depression: Acute & Prophylactic Efficacy with Citalopram

描述（由申请人提供）：该提案代表了新申请NIMH MH-0708060-01的首次重新提交，该申请要求为题为“双相抑郁症的治疗：西酞普兰的急性和预防性疗效”的赠款提供5年的资金。“要检验的主要假设与双相抑郁症抗抑郁疗效的随机临床试验有关。申请人将以双盲、安慰剂对照、随机化的方式研究5-羟色胺再摄取抑制剂（SRI）西酞普兰加入标准情绪稳定剂中对6周急性疗效以及沿着1年维持疗效的影响。此外，该申请旨在获得新的知识，抑郁症的病理生理学在双相情感障碍使用基因组学和功能性神经影像学的措施，并为第一次，治疗反应的生物学预测因子，以及与抗抑郁药（如躁狂症）的不良后果。该提案是在双相情感障碍长期抗抑郁结局的主要研究者完成R23奖励后提出的。基本原理：与单相重性抑郁症相比，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，或者它们对双相障碍病程的影响。先前的研究已经确定了双相情感障碍患者持续使用抗抑郁药的可能风险，包括诱发躁狂、混合状态、精神病或快速循环。尽管有这些潜在的风险，双相情感障碍的抑郁阶段在临床上足够引人注目，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，支持本提案的及时性。目前尚不清楚这些抗抑郁治疗在这些情况下是否有效甚至安全。此外，虽然功能性神经影像学和抗抑郁药反应的遗传预测因子已在单相抑郁症中进行了研究，但双相抑郁症的类似机制在很大程度上尚不清楚。公共卫生影响：双相抑郁症是一种恶性情绪障碍，自杀率高，工作和社会生产力明显下降。抗抑郁药是常用的，因此必须知道它们是否应该广泛使用，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疗效和安全性，几乎没有严格的科学证据。特别是考虑到一些患者使用抗抑郁药可能会明显恶化的建议，更好地了解何时使用，何时不使用，双相情感障碍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.