1/2-Ziprasidone Augmentation of SSRIs for Treatment-Resistant Depression (TRD)

1/2-齐拉西酮增强 SSRIs 治疗难治性抑郁症 (TRD)

• 批准号: 7613474
• 负责人: George I Papakostas
• 金额: $ 36.21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7613474
• 关键词: Adverse effects; Affinity; Ambulatory Care Facilities; Antidepressive Agents; Antipsychotic Agents; Anxiety; Clinical Research; Data; Dose; Double-Blind Method; Drops; Enrollment; Funding; General Hospitals; Label; Long-Term Effects; Major Depressive Disorder; Massachusetts; Measures; Pain; Patients; Phase; Placebos; Psychiatry; Relapse; Relative (related person); Resistance; Safety; Selective Serotonin Reuptake Inhibitor; Symptoms; Time; Universities; Visual; analog; atypical antipsychotic; depression; depressive symptoms; design; double-blind placebo controlled trial; experience; flexibility; improved; medical schools; novel; open label; programs; receptor; response; standard care; standard of care; treatment strategy; ziprasidone

DESCRIPTION (provided by applicant): Identifying novel treatments for resistant depression (TRD) is urgently needed to help improve the standard of care. To date, several preliminary studies have examined the use of atypical antipsychotic agents as adjuncts to standard antidepressants for TRD. However, the efficacy of this popular off-label treatment strategy has yet to be firmly established, while very little is known regarding the long-term effects (in terms of efficacy, tolerability and safety) of this treatment strategy. The atypical antipsychotic agent ziprasidone, in particular, may offer a unique opportunity to study as an adjunct for TRD for two principal reasons: I) its unique receptor-affinity profile, and, II) its favorable side-effect profile compared to the other agents in the class. Unfortunately, however, double-blind, placebo controlled trials of ziprasidone augmentation for TRD have not been conducted to date. If safe and effective as an antidepressant adjunct, ziprasidone would represent an attractive option for many of these patients who have had unsatisfactory initial response to standard treatment. If not found to be either safe or effective, the results of this proposed trial would also be highly informative given the significant proportion of TRD patients who, despite the relative paucity of data from independently-funded studies of rigorous design, are prescribed atypical antipsychotic agents off-label. The proposed study involves three phases. The first phase is an 8-week, open-label trial of an SSRI for MDD. Patients who do not experience sufficient symptom improvement following this open-label trial will be enrolled in an 8-week, double-blind, placebo controlled trial of ziprasidone augmentation (phase 2). Ziprasidone and placebo-remitters will then enter a 12-month, double-blind, extension phase (phase 3). The purpose of our study is to evaluate the efficacy, safety and tolerability of ziprasidone (20- 80mg twice-daily; flexible dose) as an adjunctive treatment in SSRI-resistant MDD. Secondary aims include: I) to determine whether ziprasidone augmentation is effective in relieving co-morbid anxious and painful symptoms of depression, and, II) to obtain preliminary data on the long-term safety and efficacy of adjunct ziprasidone. The study involves the enrollment of a total of 400 patients with MDD over the course of 5 years at either the Massachusetts General Hospital or the outpatient clinic of the department of Psychiatry at the Vanderbilt University School of Medicine. We estimate that 180 of these patients will enter the double-blind phase.

描述（由申请人提供）：迫切需要确定抗性抑郁症（TRD）的新型治疗方法以帮助改善护理标准。迄今为止，一些初步研究检查了使用非典型抗精神病药作为TRD标准抗抑郁药的辅助。但是，这种流行的标签外治疗策略的功效尚未牢固确定，而对于这种治疗策略的长期影响（在疗效，耐受性和安全性方面）知之甚少。尤其是非典型抗精神病药Ziprasidone，可能会为TRD作为辅助功能提供独特的机会，原因有两个主要原因：i）其独特的受体亲和力曲线，ii）与同类课程中的其他药物相比，其有利的副作用。然而，不幸的是，迄今为止，尚未进行双盲，安慰剂对照试验的Ziprasidone增强试验。如果作为抗抑郁药辅助手段安全有效，齐拉皮斯酮将代表许多对标准治疗初始反应不令人满意的患者的有吸引力的选择。如果未发现安全或有效，那么鉴于TRD患者的显着比例，该拟议试验的结果也将是有益的，尽管TRD患者的数据相对稀少，但由于严格设计的独立资金研究的数据相对稀少，但仍处方了非典型的抗精神病药。拟议的研究涉及三个阶段。第一阶段是对MDD的SSRI进行的为期8周的开放标签试验。这项开放标签试验后没有足够症状改善的患者将参加为期8周的双盲，安慰剂对照试验的Ziprasidone增强试验（第2阶段）。然后，Ziprasidone和安慰剂驱动器将进入12个月的双盲延伸阶段（第3阶段）。我们研究的目的是评估Ziprasidone（每天两次20-80mg;柔性剂量）的功效，安全性和耐受性，作为抗SSRI耐药的MDD的辅助治疗。次要目的包括：i）确定Ziprasidone增强是否有效缓解抑郁症的焦虑和痛苦症状，ii）获得有关辅助Ziprasidone的长期安全性和有效性的初步数据。该研究涉及在马萨诸塞州综合医院或范德比尔特大学医学院精神病学院的门诊诊所中，在5年内总共入学了400名MDD患者。我们估计其中180名患者将进入双盲阶段。