Treatment for Bipolar Depression: Acute & Prophylactic Efficacy with Citalopram

双相抑郁症的治疗：急性

• 批准号: 7261466
• 负责人: Nassir GHAEMI
• 金额: $ 41.18万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-10 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7261466
• 关键词: Acute; Affective; Alleles; Anterior; Antidepressive Agents; Award; Benefits and Risks; Biological; Bipolar Depression; Bipolar Disorder; Brain; Characteristics; Citalopram; Clinical; Comorbidity; Condition; DSM-IV; Deoxyglucose; Depressed mood; Disease; Disease remission; Doctor of Medicine; Double-Blind Method; End Point; Functional disorder; Funding; Genes; Genetic; Genetic Polymorphism; Grant; Hippocampus (Brain); Image; Insula of Reil; Intervention; Knowledge; Label; Life; Lithium; Maintenance; Major Depressive Disorder; Manic; Measures; Medical; Mental Depression; Mental disorders; Meta-Analysis; Metabolic; Mood Disorders; Mood stabilizers; Moods; Morbidity - disease rate; National Institute of Mental Health; Numbers; Observational Study; Outcome; Outcome Study; Parietal; Patients; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Positron; Premature Mortality; Principal Investigator; Productivity; Psychotic Disorders; Public Health; Randomized; Randomized Clinical Trials; Rate; Recovery; Recurrence; Research; Residual state; Risk; Risk Factors; Safety; Selective Serotonin Reuptake Inhibitor; Social Work; Source; Stabilizing Agents; Standards of Weights and Measures; Suggestion; Testing; Time; Time Study; Tricyclic Antidepressive Agents; Unipolar Depression; Variant; Virulent; Week; comparative; depressive symptoms; emission spectroscopy; experience; fluorodeoxyglucose positron emission tomography; follow-up; functional disability; functional genomics; functional status; genetic association; hypomania; lamotrigine; neuroimaging; novel; placebo controlled study; prevent; prophylactic; research study; response; safety practice; serotonin transporter; single episode major depressive disorder; suicidal risk; suicide rate

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.

描述（由申请人提供）：本提案代表新申请 NIMH MH-0708060-01 的首次重新提交，该申请要求为题为“双相抑郁的治疗：西酞普兰的急性和预防功效”的拨款提供 5 年的资助。要测试的主要假设涉及一项关于双相抑郁症抗抑郁疗效的随机临床试验。申请人将以双盲、安慰剂对照、随机的方式研究添加到标准情绪稳定剂中的血清素再摄取抑制剂 (SRI) 西酞普兰对 6 周急性疗效和 1 年维持疗效的影响。此外，该应用程序还试图通过基因组学和功能神经影像学测量来获取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以及抗抑郁药不良后果（例如躁狂症）的生物预测因子。该提案是在向主要研究者授予双相情感障碍长期抗抑郁治疗结果的 R23 奖项之后提出的。理由：与单相重度抑郁症相比，双相抑郁症是研究最少的抑郁疾病之一，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或其对双相情感障碍病程的影响的研究很少。先前的研究已经确定了持续使用抗抑郁药物治疗双相情感障碍可能存在的风险，包括诱发躁狂、混合状态、精神病或快速循环。尽管存在这些潜在风险，但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，支持了本提案的及时性。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经在单相抑郁症中进行了研究，但双相抑郁症中的类似机制在很大程度上尚不清楚。公共健康影响：躁郁症是一种严重的情绪障碍，自杀率很高，工作和社会生产力明显下降。抗抑郁药很常用，因此有必要了解它们是否应该广泛使用，或者是否应该更加限制其使用；然而，关于它们治疗双相抑郁症的功效和安全性，几乎没有严格的科学证据。特别是考虑到一些患者服用抗抑郁药物后病情可能会明显恶化，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物是一个主要的公共卫生问题。