A Multicenter, Open-Label Study to Evaluate the Long-term Safety and Efficacy of Adjunctive Brexpiprazole 2 mg Daily in Japanese Patients with Major Depressive Disorder.

IF 7.4 2区 医学 Q1 CLINICAL NEUROLOGY
CNS drugs Pub Date : 2024-12-01 Epub Date: 2024-10-18 DOI:10.1007/s40263-024-01124-w
Masaki Kato, Masako Shiosakai, Kazuo Kuwahara, Katsuhiro Iba, Yuki Shimada, Mizuki Saito, Daisuke Sekine, Kazuo Aoki, Yuki Shiomi, Teruhiko Higuchi
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引用次数: 0

Abstract

Background and objective: Inadequate response to antidepressant monotherapy is common among patients with major depressive disorder (MDD). The efficacy and safety of adjunctive brexpiprazole 2 mg/day has recently been confirmed during the 6-week, randomized, placebo-controlled phase 2/3 (BLESS) study, which evaluated brexpiprazole at 1 mg/day and 2 mg/day versus placebo as adjunctive therapy to antidepressant therapies in 740 Japanese patients with MDD and an inadequate response to antidepressant monotherapy. This study evaluated the long-term safety and efficacy of adjunctive fixed-dose brexpiprazole 2 mg/day in Japanese patients with MDD.

Methods: An open-label, 52-week study enrolled rollover patients who completed the 6-week, double-blind, randomized, placebo-controlled phase 2/3 BLESS study (NCT03697603), and de novo patients aged ≥ 65 years. Patients were titrated to fixed-dose brexpiprazole 2 mg/day from Week 1. Safety assessments included treatment-emergent adverse events (TEAEs; primary outcome) and clinical and laboratory variables. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression-Improvement (CGI-I) scale, Hamilton Depression Rating Scale (HAM-D) 17-item total score, and Sheehan Disability Scale (SDS) score.

Results: In total, 247 patients [rollover, n = 216; de novo (previously unexposed), n = 31] were included in the safety/efficacy populations, and 138 (rollover, n = 132; de novo, n = 6; 55.9%) completed the study. Common TEAEs (incidence ≥ 10%) were weight gain [33.2% (n = 82)], akathisia [23.5% (n = 58)], nasopharyngitis [21.1% (n = 52)], and somnolence [10.5% (n = 26)]. TEAEs leading to treatment discontinuation occurred in 26.7% of patients receiving brexpiprazole and 58.1% of de novo patients. The mean (SD) increase in body weight from baseline to Week 52 [observed cases (OC)] was 4.2 (6.5) kg (n = 138); 44.5% (n = 110) had weight gain ≥ 7% at any postbaseline visit. There were no cases of tardive dyskinesia and no AEs related to suicide/suicide attempts. One death occurred (unknown cause), which was unrelated to study treatment. Improvements in the MADRS total score were observed from baseline over the course of the 52-week study [mean (SD) change at Week 52 (OC): - 7.3 (8.7)] for all patients receiving brexpiprazole. The overall MADRS response rate and remission rate in patients receiving brexpiprazole was 41.3% (n = 57) and 34.8% (n = 48), respectively, at Week 52 (OC). Improvements in CGI-S, HAM-D 17 item total score, and SDS mean scores were also observed from baseline over the 52-week study, with a mean (SD) change from baseline at Week 52 (OC) of - 0.8 (1.0), - 5.9 (6.3), and - 1.0 (2.2), respectively, indicating a sustained improvement in symptoms with long-term brexpiprazole treatment.

Conclusions: This is the first study to evaluate the safety profile of brexpiprazole 2 mg/day in Japanese patients with MDD, including older adults, which is similar to previous reports, with no new safety risks, and continued efficacy over 52 weeks.

Study registration: ClinicalTrials.gov (NCT03737474; registered on 29 July 2018).

一项多中心、开放标签研究,旨在评估日本重度抑郁症患者每天服用 2 毫克布雷哌唑的长期安全性和有效性。
背景和目的:在重度抑郁障碍(MDD)患者中,对抗抑郁药单一疗法反应不充分的情况很常见。最近,为期6周的随机安慰剂对照2/3阶段(BLESS)研究证实了2毫克/天的布来哌唑辅助治疗的有效性和安全性,该研究评估了1毫克/天和2毫克/天的布来哌唑与安慰剂作为抗抑郁疗法辅助治疗的效果,740名日本重度抑郁障碍患者接受了该研究,但对抗抑郁单药治疗反应不佳。本研究评估了日本MDD患者服用固定剂量布来匹唑2毫克/天的长期安全性和有效性:这项为期52周的开放标签研究招募了完成6周双盲、随机、安慰剂对照2/3期BLESS研究(NCT03697603)的转回患者,以及年龄≥65岁的新患者。患者从第1周开始接受固定剂量的布来哌唑治疗,剂量为2毫克/天。安全性评估包括治疗突发不良事件(TEAEs;主要结果)以及临床和实验室变量。疗效评估采用蒙哥马利-阿斯伯格抑郁评定量表(MADRS)、临床总体印象-改善(CGI-I)量表、汉密尔顿抑郁评定量表(HAM-D)17项总分和希恩残疾量表(SDS)评分:共有 247 名患者[滚动,n = 216;从头开始(以前未接触过),n = 31]被纳入安全性/有效性人群,138 人(滚动,n = 132;从头开始,n = 6;55.9%)完成了研究。常见的TEAEs(发生率≥10%)为体重增加[33.2%(n = 82)]、运动障碍[23.5%(n = 58)]、鼻咽炎[21.1%(n = 52)]和嗜睡[10.5%(n = 26)]。26.7%的接受布来哌唑治疗的患者和58.1%的新患者出现了导致停药的TEAE。从基线到第52周,体重增加的平均值(标度)[观察病例(OC)]为4.2(6.5)千克(n = 138);44.5%(n = 110)的患者在基线后的任何访视中体重增加≥7%。无迟发性运动障碍病例,无与自杀/自杀未遂相关的AEs。有一例死亡病例(原因不明)与研究治疗无关。在为期52周的研究过程中,所有接受布来哌唑治疗的患者的MADRS总分均较基线有所改善[第52周(OC)的平均(标度)变化:- 7.3 (8.7)]。在第52周(OC),接受布来哌唑治疗的患者的MADRS总体反应率和缓解率分别为41.3%(n = 57)和34.8%(n = 48)。在为期52周的研究中,还观察到CGI-S、HAM-D 17项总分和SDS平均分与基线相比有所改善,第52周(OC)与基线相比的平均(标清)变化分别为-0.8(1.0)、-5.9(6.3)和-1.0(2.2),这表明布雷克普拉唑的长期治疗可持续改善症状:这是首次评估日本MDD患者(包括老年人)使用2 mg/天的布来哌唑安全性的研究,其安全性与之前的报告相似,没有新的安全风险,疗效可持续52周:ClinicalTrials.gov(NCT03737474;2018年7月29日注册)。
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来源期刊
CNS drugs
CNS drugs 医学-精神病学
CiteScore
12.00
自引率
3.30%
发文量
82
审稿时长
6-12 weeks
期刊介绍: CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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