title: Efficacy of brexpiprazole in patients with acute schizophrenia: Review of three randomized, double-blind, placebo-controlled studies.
abstract: Brexpiprazole, a serotonin-dopamine activity modulator, is a partial agonist at 5-HT1A and dopamine D2 receptors, and antagonist at 5-HT2A and noradrenaline α1B and α2C receptors, all at similar potency. Efficacy of brexpiprazole was evaluated in patients with acutely exacerbated schizophrenia in three short-term, randomized, double-blind, placebo-controlled studies. In a Phase 2 study, patients were randomized to brexpiprazole 0.25mg (fixed dose), 1.0±0.5mg, 2.5±0.5mg, 5.0±1mg (flexible-dose ranges), placebo, or aripiprazole 15±5mg. In two Phase 3 studies, patients were randomized to fixed-dose brexpiprazole 0.25mg, 1mg, 2mg, or 4mg, or placebo. For this review, brexpiprazole 2mg and 4mg arms from the Phase 3 studies were combined. Primary efficacy endpoint was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline at week 6; key secondary endpoint was change in Clinical Global Impression-Severity of illness (CGI-S) score at week 6. Primary outcome moderator analyses explored effects of sex, age, race, and illness duration. There were no statistically significant differences vs. placebo in the Phase 2 brexpiprazole and aripiprazole groups for primary and key secondary endpoints. Combined brexpiprazole 2mg (n=359) and 4mg (n=359) were superior to placebo (n=358) in change in PANSS total score (least square mean difference from placebo: -5.46, p=0.0004, and -6.69, p<0.0001, respectively) and CGI-S (-0.25, p=0.0035, and -0.38, p<0.0001, respectively). Changes from baseline in efficacy endpoints were minimal in the 0.25mg group, while the 1mg group exhibited suboptimal improvement. No relevant moderators were identified. Meta-analysis of the pivotal studies indicates brexpiprazole 2mg and 4mg are effective in treating acute schizophrenia.
authors.affiliation: The Zucker Hillside Hospital, Department of Psychiatry Research, 75-59 263rd Street, Glen Oaks, NY 11004, USA; Hofstra Northwell School of Medicine, Department of Psychiatry and Molecular Medicine, Hempstead, NY 11549, USA. Electronic address: ccorrell@nshs.edu.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Drive, 1 University Square Drive, Princeton, NJ 08540, USA. Electronic address: Aleksandar.Skuban@otsuka-us.com.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Skuban
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Drive, 1 University Square Drive, Princeton, NJ 08540, USA. Electronic address: Mary.Hobart@otsuka-us.com.
authors.forename: Mary
authors.initials: M
authors.lastname: Hobart
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Drive, 1 University Square Drive, Princeton, NJ 08540, USA. Electronic address: John.Ouyang@otsuka-us.com.
authors.forename: John
authors.initials: J
authors.lastname: Ouyang
authors.affiliation: H. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Copenhagen, Denmark. Electronic address: EMWE@Lundbeck.com.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Weiller
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Drive, 1 University Square Drive, Princeton, NJ 08540, USA. Electronic address: Catherine.Weiss@otsuka-us.com.
authors.forename: Catherine
authors.initials: C
authors.lastname: Weiss
authors.affiliation: The Zucker Hillside Hospital, Department of Psychiatry Research, 75-59 263rd Street, Glen Oaks, NY 11004, USA. Electronic address: JKane2@nshs.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
mesh_terms: D000208:Acute Disease; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D015363:Quinolones / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D015363:Quinolones; D013876:Thiophenes; C000591922:brexpiprazole
keywords: Acute; Brexpiprazole; Efficacy; Meta-analysis; Placebo; Schizophrenia