title: Overview of short- and long-term tolerability and safety of brexpiprazole in patients with schizophrenia.
abstract: Second-generation antipsychotics have demonstrated efficacy for patients with schizophrenia but are associated with wide-ranging side effects. Brexpiprazole, a serotonin-dopamine activity modulator, has demonstrated efficacy in adult patients with schizophrenia. This paper provides an overview of the safety and tolerability of brexpiprazole in patients with schizophrenia through examination of pooled safety data from one Phase 2 and two Phase 3 6-week, short-term studies, and two open-label, 52-week, long-term studies. In the short-term studies, there were no reports of treatment-emergent adverse events (TEAEs) with an incidence≥5% and twice that of placebo in patients treated with brexpiprazole 2-4mg. In the long-term studies, TEAEs reported by ≥5% of patients were schizophrenia (10.7%), insomnia (8.0%), weight increase (7.7%), headache (6.0%), and agitation (5.2%). Akathisia rates were low in the short- (5.8%, pooled brexpiprazole group) and long-term studies (4.6%). Sedation rates were low in the short- (2.3%, pooled brexpiprazole group) and long-term studies (0.9%). Mean body weight increase was 1.1kg in both short- and long-term studies. For all studies, changes from baseline to last visit in laboratory parameters, electrocardiogram values, and vital signs were small and not clinically relevant. Changes in lipid profiles or other metabolic parameters were also small. Collectively, these studies suggest that brexpiprazole was well tolerated, with a favorable safety profile that does not exhibit significant rates of important adverse events that can be seen with existing antipsychotics (akathisia, sedation, weight gain, or QTc prolongation), and therefore may provide a useful treatment option for patients with schizophrenia. ClinicalTrials.gov: NCT00905307; NCT01396421; NCT01393613; NCT01649557; NCT01397786.
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
authors.affiliation: Otsuka Pharmaceutical Development and 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 and 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 and 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 and 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: ccorrell@nshs.edu.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D015363:Quinolones / Q000009:adverse effects* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D013876:Thiophenes / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D015363:Quinolones; D013876:Thiophenes; C000591922:brexpiprazole
keywords: Akathisia; Brexpiprazole; D2 partial agonist; Safety; Schizophrenia; Sedation