Citalopram in First Episode Schizophrenia

西酞普兰在第一集精神分裂症中的应用

• 批准号: 8266009
• 负责人: DONALD C. GOFF
• 金额: $ 57.85万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-20 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8266009
• 关键词: Affect; Antidepressive Agents; Area Under Curve; Biological Markers; Biological Preservation; Brain-Derived Neurotrophic Factor; Chronic Schizophrenia; Citalopram; Clinical; Cognition; Cognitive Therapy; Disease Progression; Evaluation; Feeling suicidal; Frequencies; Genetic Markers; Genotype; Hippocampus (Brain); Hospitalization; Measurement; Measures; Mediating; Mental Depression; Methods; Neurons; Patients; Pharmacology; Placebo Control; Plasma; Prevention and Treatment Evaluation; Property; Protocols documentation; Quality of life; Recurrent disease; Relapse; Risperidone; Role; Schizophrenia; Selective Serotonin Reuptake Inhibitor; Stress; Suicide; Symptoms; Time; Visit; clinical practice; cognitive function; depressive symptoms; design; first episode schizophrenia; genetic analysis; gray matter; hippocampal atrophy; improved; neurogenesis; neurotrophic factor; placebo controlled study; primary outcome; programs; psychoeducation; response

DESCRIPTION (provided by applicant): Depressive symptoms are common early in the course of schizophrenia and are associated with poor quality of life, relapse, and suicidality. As a result, selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed, but their efficacy in first episode patients has not been studied. In a naturalistic study, prodromal patients treated with antidepressants were significantly less likely to progress to schizophrenia. SSRIs release brain derived neurotrophic factor (BDNF) which protects neurons from stress and stimulates neurogenesis. In schizophrenia, BDNF is dysregulated and BDNF genotype has been shown to predict cortical grey matter loss in first episode patients. These findings suggest that SSRI administration might protect against depression, relapse, and disease progression during the early course of the illness. Methods: We propose, in 100 first episode schizophrenia patients, a placebo-controlled, parallel-group, twelve month trial of citalopram added to risperidone treatment plus a psychoeducation protocol designed to enhance compliance and retention. Patients with significant depression or currently treated with an SSRI will be excluded from study and a CBT module targeting depression will be provided if depressive symptoms emerge during the trial. The primary outcome is depressive symptoms analyzed as the area under the curve per unit time. In addition, we will examine suicidality, negative symptoms, cognition, and relapse rates. Biomarkers will include BDNF Val66Met genotype, plasma BDNF concentrations, and gray matter volume to assess a possible relationship between SSRI treatment, enhanced BDNF activity, preservation of cortical gray matter, and improved clinical course. Significance: The evaluation of SSRI treatment for depressive symptoms, suicidal ideation and relapse in first episode patients is of considerable clinical importance. In addition, the potential role of SSRI-induced BDNF release in promoting neurogenesis and improving the course of the illness offers an exciting new direction for the pharmacology of schizophrenia.

描述(由申请人提供)：抑郁症状是精神分裂症病程早期的常见症状，与生活质量差、复发和自杀有关。因此，选择性5-羟色胺再摄取抑制剂(SSRI)经常被开出，但其对首发患者的疗效尚未被研究。在一项自然主义研究中，接受抗抑郁药物治疗的前驱症状患者进展为精神分裂症的可能性显著降低。SSRIs释放脑源性神经营养因子(BDNF)，保护神经元免受压力并刺激神经发生。在精神分裂症患者中，BDNF基因表达失调，BDNF基因可以预测首发患者的皮质灰质丢失。这些发现表明，在疾病的早期，SSRI给药可能防止抑郁、复发和疾病进展。方法：我们建议，在100名首发精神分裂症患者中，在利培酮治疗的基础上加用西酞普兰12个月，再加上旨在提高依从性和保留性的心理教育方案，作为安慰剂对照的平行分组试验。患有严重抑郁症或正在接受SSRI治疗的患者将被排除在研究之外，如果在试验期间出现抑郁症状，将提供针对抑郁症的CBT模块。主要结果是抑郁症状被分析为单位时间曲线下的面积。此外，我们还将检查自杀、阴性症状、认知和复发率。生物标志物将包括BDNF Val66Met基因型、血浆BDNF浓度和灰质体积，以评估SSRI治疗、增强BDNF活性、保留皮质灰质和改善临床病程之间的可能关系。意义：评价SSRI治疗首发患者的抑郁症状、自杀意念和复发具有相当重要的临床意义。此外，SSRI诱导的BDNF释放在促进神经发生和改善病程方面的潜在作用为精神分裂症的药理学提供了一个令人兴奋的新方向。