Defining treatment-resistant schizophrenia and response to antipsychotics: A review and recommendation

Takefumi Suzuki, Gary Remington, Benoit H. Mulsant, Hiroyuki Uchida, Tarek K. Rajji, Ariel Graff-Guerrero, Masaru Mimura, David C. Mamo

Research output: Contribution to journalArticlepeer-review

137 Citations (Scopus)


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 ≥. 600. mg/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.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalPsychiatry Research
Issue number1-2
Publication statusPublished - 2012 May 15


  • Antipsychotics
  • Definition
  • Functioning
  • Response
  • Symptoms
  • Treatment-resistant schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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