Michael Bauer, Nanco Hefting, Annika Lindsten, Mette Krog Josiassen, Mary Hobart
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The primary endpoint was full remission: Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤10 and ≥50% decrease from randomisation (i.e. baseline) in MADRS total score for at least 8 consecutive weeks.</p><p><strong>Results: </strong>The primary efficacy analysis failed to show a statistically significant difference between the proportions of patients on ADT+brexpiprazole (21.4%) and ADT+placebo (24.9%) achieving full remission; odds ratio: 0.83; p=0.2641. The secondary endpoint of change from baseline to Week 6 in MADRS total score showed no difference between ADT+brexpiprazole and ADT+placebo (-0.4; p=0.3259). The most frequent treatment-emergent adverse event (TEAE) in patients receiving ADT+brexpiprazole was weight increased (9.5% vs. 5.0% in ADT+placebo). The incidence of TEAEs leading to withdrawal in the randomised treatment period was 6.3% in the ADT+brexpiprazole group and 3.4% in the ADT+placebo group.</p><p><strong>Conclusion: </strong>Adjunctive brexpiprazole did not differentiate from ADT+placebo on the primary endpoint of full remission. A number of design elements in this previously untried study design may have contributed to the study result. Brexpiprazole was well tolerated.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/neu.2018.23","citationCount":"21","resultStr":"{\"title\":\"A randomised, placebo-controlled 24-week study evaluating adjunctive brexpiprazole in patients with major depressive disorder.\",\"authors\":\"Michael Bauer, Nanco Hefting, Annika Lindsten, Mette Krog Josiassen, Mary Hobart\",\"doi\":\"10.1017/neu.2018.23\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To evaluate brexpiprazole adjunctive to antidepressant therapies (ADTs) as maintenance treatment in patients with major depressive disorder with inadequate response to ADT, utilising a novel study design.</p><p><strong>Methods: </strong>The study comprised an 8-week prospective treatment period with open-label ADT with double-blind placebo treatment and a 24-week randomised treatment period. Investigators and patients were blinded to treatment periods, randomisation criteria, and timing of randomisation. Patients with early response to open-label ADT were withdrawn at Week 6. Patients fulfilling criteria for inadequate response were randomised to ADT+brexpiprazole 1-3 mg/day, or ADT+placebo. The primary endpoint was full remission: Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤10 and ≥50% decrease from randomisation (i.e. baseline) in MADRS total score for at least 8 consecutive weeks.</p><p><strong>Results: </strong>The primary efficacy analysis failed to show a statistically significant difference between the proportions of patients on ADT+brexpiprazole (21.4%) and ADT+placebo (24.9%) achieving full remission; odds ratio: 0.83; p=0.2641. The secondary endpoint of change from baseline to Week 6 in MADRS total score showed no difference between ADT+brexpiprazole and ADT+placebo (-0.4; p=0.3259). 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引用次数: 21
摘要
目的:采用一种新颖的研究设计,评估brexpiprazole辅助抗抑郁治疗(ADTs)作为维持治疗对ADT反应不足的重度抑郁症患者的疗效。方法:该研究包括8周的前瞻性治疗期,采用开放标签ADT加双盲安慰剂治疗,以及24周的随机治疗期。研究者和患者对治疗期、随机化标准和随机化时间不知情。对开放标签ADT有早期反应的患者在第6周停药。满足不良反应标准的患者被随机分配到ADT+brexpiprazole (1- 3mg /天)或ADT+安慰剂组。主要终点为完全缓解:Montgomery-Åsberg抑郁评定量表(MADRS)总分≤10,MADRS总分从随机化(即基线)至少连续8周下降≥50%。结果:初步疗效分析未显示ADT+brexpiprazole(21.4%)与ADT+placebo(24.9%)达到完全缓解的患者比例有统计学差异;优势比:0.83;p = 0.2641。从基线到第6周MADRS总分变化的次要终点显示ADT+brexpiprazole和ADT+placebo之间没有差异(-0.4;p = 0.3259)。在接受ADT+brexpiprazole的患者中,最常见的治疗不良事件(TEAE)是体重增加(9.5% vs. ADT+安慰剂组5.0%)。在随机治疗期间,ADT+brexpiprazole组的teae导致停药的发生率为6.3%,而ADT+安慰剂组为3.4%。结论:辅助布雷吡拉唑与ADT+安慰剂在完全缓解的主要终点上没有区别。在这个以前未尝试过的研究设计中,许多设计元素可能对研究结果有贡献。Brexpiprazole耐受性良好。
A randomised, placebo-controlled 24-week study evaluating adjunctive brexpiprazole in patients with major depressive disorder.
Objective: To evaluate brexpiprazole adjunctive to antidepressant therapies (ADTs) as maintenance treatment in patients with major depressive disorder with inadequate response to ADT, utilising a novel study design.
Methods: The study comprised an 8-week prospective treatment period with open-label ADT with double-blind placebo treatment and a 24-week randomised treatment period. Investigators and patients were blinded to treatment periods, randomisation criteria, and timing of randomisation. Patients with early response to open-label ADT were withdrawn at Week 6. Patients fulfilling criteria for inadequate response were randomised to ADT+brexpiprazole 1-3 mg/day, or ADT+placebo. The primary endpoint was full remission: Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤10 and ≥50% decrease from randomisation (i.e. baseline) in MADRS total score for at least 8 consecutive weeks.
Results: The primary efficacy analysis failed to show a statistically significant difference between the proportions of patients on ADT+brexpiprazole (21.4%) and ADT+placebo (24.9%) achieving full remission; odds ratio: 0.83; p=0.2641. The secondary endpoint of change from baseline to Week 6 in MADRS total score showed no difference between ADT+brexpiprazole and ADT+placebo (-0.4; p=0.3259). The most frequent treatment-emergent adverse event (TEAE) in patients receiving ADT+brexpiprazole was weight increased (9.5% vs. 5.0% in ADT+placebo). The incidence of TEAEs leading to withdrawal in the randomised treatment period was 6.3% in the ADT+brexpiprazole group and 3.4% in the ADT+placebo group.
Conclusion: Adjunctive brexpiprazole did not differentiate from ADT+placebo on the primary endpoint of full remission. A number of design elements in this previously untried study design may have contributed to the study result. Brexpiprazole was well tolerated.
期刊介绍:
Acta Neuropsychiatrica is an international journal focussing on translational neuropsychiatry. It publishes high-quality original research papers and reviews. The Journal''s scope specifically highlights the pathway from discovery to clinical applications, healthcare and global health that can be viewed broadly as the spectrum of work that marks the pathway from discovery to global health.