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

描述(由申请人提供)：迫切需要为难治性抑郁症(TRD)寻找新的治疗方法，以帮助提高护理标准。到目前为止，几项初步研究已经检查了非典型抗精神病药物作为标准抗抑郁药的辅助治疗TRD的情况。然而，这种流行的非标签治疗策略的有效性尚未得到确定，而关于这种治疗策略的长期影响(就有效性、耐受性和安全性而言)也知之甚少。特别是，非典型抗精神病药物齐拉西酮可能提供一个独特的机会作为TRD的辅助药物进行研究，主要原因有两个：i)其独特的受体亲和力特征，以及ii)与同类药物相比其良好的副作用特征。然而，不幸的是，到目前为止还没有进行齐拉西酮强化TRD的双盲、安慰剂对照试验。如果作为抗抑郁药的辅助药物安全有效，齐拉西酮对许多对标准治疗的初始反应不满意的患者来说将是一个有吸引力的选择。如果不被发现是安全或有效的，这项拟议试验的结果也将是非常有信息量的，因为尽管严格设计的独立资助研究的数据相对匮乏，但TRD患者中有相当大一部分人在标签外开了非典型抗精神病药物。建议的研究分三个阶段进行。第一阶段是针对MDD的SSRI的为期8周的开放标签试验。在这项开放标签试验后症状没有得到充分改善的患者将参加为期8周的双盲安慰剂对照齐拉西酮强化试验(第2阶段)。然后，齐拉西酮和安慰剂汇款患者将进入为期12个月的双盲延期阶段(第三阶段)。本研究的目的是评价齐拉西酮(20-80 mg，每日2次，剂量灵活)作为辅助治疗耐SSRI的MDD的有效性、安全性和耐受性。次要目标包括：i)确定Ziprasidone增强剂是否能有效缓解抑郁症的焦虑和疼痛症状，以及ii)获得有关辅助性Ziprasidone长期安全性和有效性的初步数据。这项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系的门诊诊所招募总共400名MDD患者，为期5年。我们估计，其中180名患者将进入双盲期。

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.