PMID- 37933521
OWN - NLM
STAT- MEDLINE
DCOM- 20240202
LR  - 20240206
IS  - 1440-1819 (Electronic)
IS  - 1323-1316 (Linking)
VI  - 78
IP  - 2
DP  - 2024 Feb
TI  - Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major 
      depressive disorder following inadequate response to antidepressants: a phase 
      2/3, randomized, double-blind (BLESS) study.
PG  - 113-122
LID - 10.1111/pcn.13615 [doi]
AB  - AIMS: Inadequate antidepressant response interrupts effective treatment of major 
      depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and 
      safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate 
      antidepressant therapy (ADT) response. METHODS: This placebo-controlled, 
      randomized, multicenter, parallel-group phase 2/3 study randomized Japanese MDD 
      patients (Hamilton Rating Scale for Depression 17-item total score >/= 14; 
      historical inadequate response to 1-3 ADTs) with inadequate response to 8-week 
      single-blind, prospective SSRI/SNRI treatment to 6-week adjunctive treatment with 
      brexpiprazole 1 mg, 2 mg, or placebo. The primary endpoint was change in 
      Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline. 
      Secondary endpoints included MADRS response, remission rate, and Clinical Global 
      Impression-Improvement score. Safety was comprehensively evaluated, especially 
      regarding antipsychotic adverse events (AEs). RESULTS: Of 1194 screened patients, 
      740 were randomized and 736 (1 mg, n = 248; 2 mg, n = 245; placebo, n = 243) had 
      >/=1 baseline/post-baseline MADRS total score. The LSM (SE) change from baseline in 
      MADRS total score at Week 6 by MMRM analysis was -8.5 (0.47) with brexpiprazole 1 
      mg, -8.2 (0.47) with brexpiprazole 2 mg, and -6.7 (0.47) with placebo 
      (placebo-adjusted LSM difference [95% CI]: 1 mg, -1.7 [-3.0, -0.4]; P = 0.0089; 
      2 mg, -1.4 [-2.7, -0.1]; P = 0.0312). Secondary efficacy results supported the 
      primary endpoint. Brexpiprazole was generally well tolerated. CONCLUSION: 
      Brexpiprazole 1 mg daily was an appropriate starting dose and both 1 mg and 2 mg 
      daily were effective and well tolerated as adjunctive therapy for Japanese MDD 
      patients not adequately responsive to ADT.
CI  - (c) 2023 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley 
      & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.
FAU - Kato, Masaki
AU  - Kato M
AUID- ORCID: 0000-0001-6727-7272
AD  - Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
FAU - Shiosakai, Masako
AU  - Shiosakai M
AD  - Clinical Development, Headquarters of Clinical Development Otsuka Pharmaceutical 
      Co. Ltd., Tokyo, Japan.
FAU - Kuwahara, Kazuo
AU  - Kuwahara K
AD  - Clinical Development, Headquarters of Clinical Development Otsuka Pharmaceutical 
      Co. Ltd., Tokyo, Japan.
FAU - Iba, Katsuhiro
AU  - Iba K
AD  - Clinical Development, Headquarters of Clinical Development Otsuka Pharmaceutical 
      Co. Ltd., Osaka, Japan.
FAU - Shimada, Yuki
AU  - Shimada Y
AD  - Clinical Development, Headquarters of Clinical Development Otsuka Pharmaceutical 
      Co. Ltd., Tokyo, Japan.
FAU - Saito, Mizuki
AU  - Saito M
AD  - Clinical Development, Headquarters of Clinical Development Otsuka Pharmaceutical 
      Co. Ltd., Tokyo, Japan.
FAU - Isogai, Yuki
AU  - Isogai Y
AUID- ORCID: 0009-0003-3483-3174
AD  - Medical Affairs, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan.
FAU - Sekine, Daisuke
AU  - Sekine D
AD  - Medical Affairs, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan.
FAU - Aoki, Kazuo
AU  - Aoki K
AD  - Medical Affairs, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan.
FAU - Koga, Nobuyuki
AU  - Koga N
AD  - Medical Affairs, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
FAU - Higuchi, Teruhiko
AU  - Higuchi T
AD  - Japan Depression Center, Tokyo, Japan.
AD  - National Center of Neurology and Psychiatry, Tokyo, Japan.
LA  - eng
GR  - N/A/Otsuka Pharmaceutical Co., Ltd./
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20231201
PL  - Australia
TA  - Psychiatry Clin Neurosci
JT  - Psychiatry and clinical neurosciences
JID - 9513551
RN  - 2J3YBM1K8C (brexpiprazole)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Thiophenes)
RN  - 0 (Quinolones)
SB  - IM
MH  - Humans
MH  - *Depressive Disorder, Major/drug therapy
MH  - Prospective Studies
MH  - Japan
MH  - Single-Blind Method
MH  - Drug Therapy, Combination
MH  - Antidepressive Agents/adverse effects
MH  - Treatment Outcome
MH  - Double-Blind Method
MH  - *Thiophenes
MH  - *Quinolones
OTO - NOTNLM
OT  - Japanese
OT  - adjunctive therapy
OT  - antipsychotic
OT  - brexpiprazole
OT  - major depressive disorder
EDAT- 2023/11/07 06:45
MHDA- 2024/02/02 06:43
CRDT- 2023/11/07 04:33
PHST- 2023/10/27 00:00 [revised]
PHST- 2023/09/07 00:00 [received]
PHST- 2023/11/04 00:00 [accepted]
PHST- 2024/02/02 06:43 [medline]
PHST- 2023/11/07 06:45 [pubmed]
PHST- 2023/11/07 04:33 [entrez]
AID - 10.1111/pcn.13615 [doi]
PST - ppublish
SO  - Psychiatry Clin Neurosci. 2024 Feb;78(2):113-122. doi: 10.1111/pcn.13615. Epub 
      2023 Dec 1.