title: Therapeutic improvements expected in the near future for schizophrenia and schizoaffective disorder: an appraisal of phase III clinical trials of schizophrenia-targeted therapies as found in US and EU clinical trial registries.
abstract: BACKGROUND
  In this review, the authors describe medications in phase III of clinical development for schizophrenia and schizoaffective disorder, and provide an opinion on how current treatment can be improved in the near future.
  
  
  METHODS
  Recent (post 2013) phase III clinical trials of schizophrenia-targeted therapies were found in US and EU clinical trial registries. Two hundred fifty-three trials were identified, that included 16 investigational compounds. The antipsychotics brexpiprazole and cariprazine have been approved in the US, and although both are dopamine D2 receptor partial agonists, they differ markedly in their pharmacodynamic profiles. Encenicline and valbenazine are first-in-class candidates for treatment of cognitive impairment associated with schizophrenia (CIAS) and tardive dyskinesia, respectively. Eleven add-on compounds were previously approved for other therapeutic indications and are for the most part being studied at academic medical centers and smaller pharmaceutical companies for negative symptoms and CIAS or for specific populations (comorbidities, antipsychotic-induced obesity).
  
  
  CONCLUSIONS
  Promising new agents are emerging for schizophrenia and schizoaffective disorder. In addition to better-tolerated antipsychotics that treat positive symptoms, we could see the arrival of the first effective drug for negative symptoms and CIAS, which would strongly facilitate the ultimate goal of recovery in persons with schizophrenia.
authors.affiliation: a INSERM U999, Université Paris-Sud et Hôpital Marie Lannelongue , Le Plessis -Robinson , France.|b Pharmacology and Therapeutics, Craven , Villemoisson-sur-Orge , France.
authors.forename: Ricardo P
authors.initials: RP
authors.lastname: Garay
authors.affiliation: c Department of Psychiatry and Behavioral Sciences , New York Medical College , Valhalla , NY , USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.affiliation: d Centre Médico-Psychologique B , CHU, Clermont-Ferrand, EA U7280, Université d'Auvergne , Clermont-Ferrand , France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Samalin
authors.affiliation: e Department of Psychiatry , National Taiwan University Hospital , Taipei , Taiwan.
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Liu
authors.affiliation: f Department of Drug Design & Pharmacology , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Morten S
authors.initials: MS
authors.lastname: Thomsen
authors.affiliation: g The Zucker Hillside Hospital , Psychiatry Research, North Shore - Long Island Jewish Health System , Glen Oaks , NY , USA.|h Hofstra North Shore LIJ School of Medicine , Hempstead , NY , USA.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.affiliation: b Pharmacology and Therapeutics, Craven , Villemoisson-sur-Orge , France.
authors.forename: Ahcène
authors.initials: A
authors.lastname: Hameg
authors.affiliation: d Centre Médico-Psychologique B , CHU, Clermont-Ferrand, EA U7280, Université d'Auvergne , Clermont-Ferrand , France.
authors.forename: Pierre-Michel
authors.initials: PM
authors.lastname: Llorca
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D003072:Cognition Disorders / Q000188:drug therapy; D005062:European Union; D006801:Humans; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000523:psychology; D012042:Registries; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D014481:United States
chemical_list: D014150:Antipsychotic Agents
keywords: Schizophrenia; brexpiprazole; cariprazine; clinical trials; encenicline; phase III; valbenazine