Oakes Tina M, Dellva Mary Anne, Waterman Karen, Greenbaum Michael, Poppe Christopher, Goldberger Celine, Ahl Jonna, Perahia David G
Lilly Research Laboratories, Eli Lilly and Company , Indianapolis, IN , USA.
Curr Med Res Opin. 2015 Jun;31(6):1179-89. doi: 10.1185/03007995.2015.1037732. Epub 2015 May 6.
When patients with major depressive disorder (MDD) are partial responders to antidepressant therapy, adjunctive treatment with an agent that has a different mode of action may provide additional benefit. We investigated the efficacy of edivoxetine, a highly selective norepinephrine reuptake inhibitor (NRI), as adjunctive treatment to selective serotonin reuptake inhibitors (SSRIs) in the prevention of re-emergence of depressive symptoms in patients with MDD (ClinicalTrials.gov identifier: NCT01299272).
Adult outpatients with MDD who were partial responders to SSRI treatment (N = 1249) entered an open-label 8 week flexibly dosed (12-18 mg/day) adjunctive edivoxetine period. Patients who achieved remission (Montgomery-Åsberg Depression Rating Scale total score ≤10 at week 8) entered a 12 week open-label fixed-dose (12 mg or 18 mg/day) stabilization period, and those still in remission at each of weeks 18, 19, and 20 were randomized to continue treatment at the same dose of edivoxetine or switch to placebo for a 24 week double-blind withdrawal period. All patients remained on SSRI therapy throughout the study. The primary outcome was time to re-emergence of depressive symptoms during double-blind withdrawal.
Two hundred and ninety-four patients were randomized to continue adjunctive edivoxetine and 292 were switched to adjunctive placebo. Comparing adjunctive edivoxetine with adjunctive placebo, differences were not significant for time to re-emergence of symptoms (Kaplan-Meier log-rank p = 0.485), rates of symptom re-emergence (9.9% vs 8.2%, p = 0.565) or rates of sustained remission (75.4% vs 76.7%, p = 0.771). Treatment-emergent adverse events were consistent with the noradrenergic mechanism of action.
Edivoxetine failed to demonstrate superiority vs placebo as adjunctive treatment in the prevention of symptom re-emergence during maintenance treatment in SSRI partial responders with MDD. While no selective NRIs are approved for adjunctive treatment to SSRIs in MDD, the use of NRIs in this population is nonetheless accepted practice, but our data do not support the efficacy of this approach.
当重度抑郁症（MDD）患者对抗抑郁治疗仅部分有效时，联合使用一种具有不同作用模式的药物可能会带来额外益处。我们研究了高选择性去甲肾上腺素再摄取抑制剂（NRI）依地西汀作为选择性5-羟色胺再摄取抑制剂（SSRI）的辅助治疗手段，用于预防MDD患者抑郁症状再次出现的疗效（ClinicalTrials.gov标识符：NCT01299272）。
对SSRI治疗仅部分有效的成年MDD门诊患者（N = 1249）进入为期8周的开放标签依地西汀辅助治疗期，剂量灵活（12 - 18毫克/天）。达到缓解的患者（蒙哥马利 - 艾斯伯格抑郁量表总分在第8周时≤10）进入为期12周的开放标签固定剂量（12毫克或18毫克/天）巩固期，在第18、19和20周仍处于缓解状态的患者被随机分配，以相同剂量的依地西汀继续治疗或换用安慰剂进行为期24周的双盲撤药期。在整个研究过程中，所有患者均继续接受SSRI治疗。主要结局指标是双盲撤药期内抑郁症状再次出现的时间。
294例患者被随机分配继续接受依地西汀辅助治疗，292例患者换用安慰剂辅助治疗。将依地西汀辅助治疗与安慰剂辅助治疗进行比较，症状再次出现的时间（Kaplan - Meier对数秩检验p = 0.485）、症状再次出现的发生率（9.9%对8.2%，p = 0.565）或持续缓解率（75.4%对76.7%，p = 0.771）差异均无统计学意义。治疗中出现的不良事件与去甲肾上腺素能作用机制一致。
在预防MDD且对SSRI仅部分有效的患者维持治疗期间症状再次出现方面，依地西汀作为辅助治疗未显示出优于安慰剂的效果。虽然目前尚无选择性NRI被批准用于MDD患者SSRI的辅助治疗，但在该人群中使用NRI仍是普遍做法，不过我们的数据并不支持这种方法的疗效。
