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

描述（由申请人提供）：迫切需要确定难治性抑郁症（TRD）的新治疗方法，以帮助提高护理标准。迄今为止，一些初步研究已经检验了使用非典型抗精神病药物作为标准抗抑郁药的辅助治疗TRD。然而，这种流行的标签外治疗策略的疗效尚未得到确定，而对这种治疗策略的长期效果（在疗效、耐受性和安全性方面）知之甚少。特别是非典型抗精神病药物齐拉西酮，可能提供了一个独特的机会来研究作为TRD的辅助药物，主要有两个原因：1)其独特的受体亲和力；2)与同类药物中其他药物相比，其良好的副作用。然而，不幸的是，迄今为止还没有进行齐拉西酮增强治疗TRD的双盲安慰剂对照试验。如果齐拉西酮作为抗抑郁药物的辅助治疗是安全有效的，那么对于许多最初对标准治疗反应不满意的患者来说，齐拉西酮将是一个有吸引力的选择。尽管独立资助的严格设计的研究的数据相对缺乏，但考虑到很大比例的TRD患者在标签外使用非典型抗精神病药物，如果没有被发现是安全或有效的，这项拟议试验的结果也将具有很高的信息性。拟议的研究包括三个阶段。第一阶段是一项为期8周的SSRI治疗重度抑郁症的开放标签试验。在这项开放标签试验后，症状没有得到充分改善的患者将被纳入一项为期8周、双盲、安慰剂对照的齐拉西酮增强试验（2期）。齐拉西酮和安慰剂缓解者将进入12个月的双盲延长期（第三期）。本研究的目的是评价齐拉西酮（20- 80mg，每日2次，灵活剂量）作为辅助治疗ssri耐药MDD的疗效、安全性和耐受性。次要目的包括：1)确定齐拉西酮增强是否能有效缓解抑郁症的共病焦虑和疼痛症状，2)获得辅助齐拉西酮长期安全性和有效性的初步数据。这项研究包括在马萨诸塞州总医院或范德比尔特大学医学院精神病学门诊共登记了400名重度抑郁症患者，时间长达5年。我们估计其中180名患者将进入双盲阶段。

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.