title: Defining treatment-resistant schizophrenia and response to antipsychotics: a review and recommendation.
abstract: Treatment-resistant schizophrenia (TRS) has been defined mainly by severity of (positive) symptoms and response to antipsychotics derived from a relative change in the representative scales (most frequently ≥ 20% decrease in the Positive and Negative Syndrome Scale: PANSS), but these definitions have not necessarily been consistent. Integrating past evidence and real-world practicability, we propose that TRS be defined by at least two failed adequate trials with different antipsychotics (at chlorpromazine-equivalent doses of ≥ 600mg/day for ≥ 6 consecutive weeks) that could be retrospective or preferably include prospective failure to respond to one or more antipsychotic trials. In addition, our proposed criteria require both a score of ≥ 4 on the Clinical Global Impression (CGI)-Severity and a score of ≤ 49 on the Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz) or ≤ 50 on the Global Assessment of Functioning (GAF) scales to define TRS. Once TRS is established, we propose that subsequent treatment response be defined based on a CGI-Change score of ≤ 2, a ≥ 20% decrease on the total PANSS or Brief Psychiatric Rating Scale (BPRS) scores, and an increase of ≥ 20 points on the FACT-Sz or GAF. While these suggestions provide a pragmatic framework for TRS classification, they need to be tested in future trials.
authors.affiliation: Department of Neuropsychiatry, Keio University, School of Medicine, Tokyo, Japan. takefumi@oak.dti.ne.jp
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D004351:Drug Resistance; D006801:Humans; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents