PMID- 33691517
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220425
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Print)
IS  - 0269-8811 (Linking)
VI  - 35
IP  - 8
DP  - 2021 Aug
TI  - Two randomized, double-blind, placebo-controlled trials and one open-label, 
      long-term trial of brexpiprazole for the acute treatment of bipolar mania.
PG  - 971-982
LID - 10.1177/0269881120985102 [doi]
AB  - BACKGROUND: Brexpiprazole is a dopamine/serotonin receptor partial agonist (D(2), 
      5-HT(1A)) and antagonist (5-HT(2A)) approved for treatment of schizophrenia and 
      major depressive disorder (adjunct to antidepressants). AIMS: This study aimed to 
      investigate brexpiprazole as monotherapy in acute mania (bipolar I disorder) in 
      two short-term (ST) studies (study 080 and study 081) and one open-label (OL) 
      extension (study 083). METHODS: ST studies were three-week randomized, 
      double-blind, flexible dose (2-4 mg/day), placebo-controlled studies. The primary 
      endpoint was mean change in Young Mania Rating Scale (YMRS) total score from 
      baseline to day 21. The OL study was a 26-week flexible dose (2-4 mg/day) study 
      for patients completing the ST studies. RESULTS: A total of 164 and 158 (study 
      080) and 170 and 162 (study 081) inpatients with DSM-5 mania with/without mixed 
      features were randomized to placebo or brexpiprazole, respectively. The primary 
      analyses did not show a statistically significant difference between 
      brexpiprazole and placebo: study 080: least squares mean difference (95% 
      confidence limits): 0.14 (-1.74, 2.03), p = 0.8797; study 081: -1.62 (-3.56, 
      0.32), p = 0.1011. OL study patients (n = 381) demonstrated a gradual improvement 
      in YMRS total score. Akathisia was the only adverse event, with an incidence of 
      ⩾5% with brexpiprazole and more than placebo in the ST studies, or ⩾5% in the OL 
      study. Brexpiprazole was more efficacious in patients with impaired or no insight 
      (predominantly EU patients) than in patients with excellent insight 
      (predominantly US patients). CONCLUSIONS: Further studies are necessary to 
      address the potential efficacy of brexpiprazole in acute mania, which should 
      ensure that the study sample is severe enough (especially with regard to 
      insight), and that the dose/titration schedule is not too modest.
FAU - Vieta, Eduard
AU  - Vieta E
AUID- ORCID: 0000-0002-0548-0053
AD  - Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, 
      CIBERSAM, Barcelona, Spain.
FAU - Sachs, Gary
AU  - Sachs G
AD  - Massachusetts General Hospital, Boston, USA.
FAU - Chang, Denise
AU  - Chang D
AD  - Otsuka Pharmaceutical Development and Commercialization, Inc., Princeton, USA.
FAU - Hellsten, Johan
AU  - Hellsten J
AD  - H. Lundbeck A/S, Valby, Denmark.
FAU - Brewer, Claudette
AU  - Brewer C
AD  - Otsuka Pharmaceutical Development and Commercialization, Inc., Princeton, USA.
FAU - Peters-Strickland, Timothy
AU  - Peters-Strickland T
AD  - Otsuka Pharmaceutical Development and Commercialization, Inc., Princeton, USA.
FAU - Hefting, Nanco
AU  - Hefting N
AD  - H. Lundbeck A/S, Valby, Denmark.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20210310
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Dopamine Agonists)
RN  - 0 (Quinolones)
RN  - 0 (Serotonin Agents)
RN  - 0 (Thiophenes)
RN  - 2J3YBM1K8C (brexpiprazole)
SB  - IM
MH  - Adult
MH  - Bipolar Disorder/*drug therapy/physiopathology
MH  - Dopamine Agonists/*administration & dosage/adverse effects/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Psychiatric Status Rating Scales
MH  - Quinolones/*administration & dosage/adverse effects/pharmacology
MH  - Serotonin Agents/*administration & dosage/adverse effects/pharmacology
MH  - Thiophenes/*administration & dosage/adverse effects/pharmacology
MH  - Treatment Outcome
PMC - PMC8366183
OTO - NOTNLM
OT  - Bipolar I disorder
OT  - brexpiprazole
OT  - clinical trial
OT  - dopamine
OT  - insight
OT  - serotonin receptor partial agonist and antagonist
COIS- Data availability: To submit inquiries related to Otsuka clinical research, or to 
      request access to individual participant data (IPD) associated with any Otsuka 
      clinical trial, please visit https://clinical-trials.otsuka.com/. For all 
      approved IPD access requests, Otsuka will share anonymized IPD on a remotely 
      accessible data sharing platform. Declaration of conflicting interests: The 
      authors declared the following potential conflicts of interest with respect to 
      the research, authorship, and/or publication of this article: E.V. has received 
      grants and served as consultant, advisor, or CME speaker for the following 
      entities: AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, 
      Galenica, Janssen, Lundbeck, Novartis, Otsuka, Richter, Sage, Sanofi-Aventis, and 
      Takeda, outside the submitted work. G.S. reports consulting fees from 
      AstraZeneca, Blackthorne, Intra-Cellular Therapies, Otsuka, Pfizer, Sunovion, 
      Supernus, Takeda, and Teva outside the submitted work and is a full-time employee 
      of Signant Health. D.C., C.B., and T.P.-S. are full-time employees of Otsuka 
      Pharmaceutical Development and Commercialization, Inc., Princeton, NJ, USA. J.H. 
      and N.H. are full-time employees of H. Lundbeck A/S, Valby, Denmark.
EDAT- 2021/03/12 06:00
MHDA- 2022/02/03 06:00
PMCR- 2021/08/16
CRDT- 2021/03/11 05:39
PHST- 2021/03/12 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/03/11 05:39 [entrez]
PHST- 2021/08/16 00:00 [pmc-release]
AID - 10.1177_0269881120985102 [pii]
AID - 10.1177/0269881120985102 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2021 Aug;35(8):971-982. doi: 10.1177/0269881120985102. Epub 
      2021 Mar 10.