Subtyping schizophrenia by treatment response: Antipsychotic development and the central role of positive symptoms

Jimmy Lee, Hiroyoshi Takeuchi, Gagan Fervaha, Gwen Li Sin, George Foussias, Ofer Agid, Saeed Farooq, Gary Remington

Research output: Contribution to journalReview article

20 Citations (Scopus)

Abstract

We have recently proposed a model for subtyping schizophrenia based on antipsychotic (AP) treatment response. Evidence suggests that APs, both old and new, are comparable in terms of efficacy; however, one AP, clozapine, is uniquely effective in one subgroup of patients (that is, those with treatment-resistant schizophrenia [TRS]). This permits us to subdivide schizophrenia into 3 specific groups: AP responsive, clozapine responsive, and clozapine resistant. Here, we integrate this model with current criteria related to TRS and ultraresistant schizophrenia, the latter referred to in our model as clozapine resistant. We suggest several modifications to existing criteria, in line with current evidence and practice patterns, particularly emphasizing the need to focus on positive symptoms. While APs can favourably impact numerous dimensions related to schizophrenia, it is their effect on positive symptoms that distinguishes them from other psychotropics. Further, it is positive symptoms that are central to AP and clozapine resistance, and it is these people that place the greatest demands on acute and long-term inpatient resources. In moving AP development forward, we advocate specifically focusing on positive symptoms and capitalizing on the evidence we have of 3 subtypes of psychosis (that is, positive symptoms) based on treatment response, implicating 3 distinguishable forms of underlying pathophysiology. Conversely, pooling these groups risks obfuscating potentially identifiable differences. Such a position does not challenge the importance of dopamine D2 receptor blockade, but rather highlights the need to better isolate those other subgroups that require something more or entirely different.

Original languageEnglish
Pages (from-to)515-522
Number of pages8
JournalCanadian Journal of Psychiatry
Volume60
Issue number11
Publication statusPublished - 2015 Nov 1

Fingerprint

Clozapine
Antipsychotic Agents
Schizophrenia
Therapeutics
Dopamine D2 Receptors
Psychotic Disorders
Inpatients

Keywords

  • Antipsychotic
  • Clozapine
  • Psychosis
  • Treatment-resistant
  • Ultraresistant

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Subtyping schizophrenia by treatment response : Antipsychotic development and the central role of positive symptoms. / Lee, Jimmy; Takeuchi, Hiroyoshi; Fervaha, Gagan; Sin, Gwen Li; Foussias, George; Agid, Ofer; Farooq, Saeed; Remington, Gary.

In: Canadian Journal of Psychiatry, Vol. 60, No. 11, 01.11.2015, p. 515-522.

Research output: Contribution to journalReview article

Lee, J, Takeuchi, H, Fervaha, G, Sin, GL, Foussias, G, Agid, O, Farooq, S & Remington, G 2015, 'Subtyping schizophrenia by treatment response: Antipsychotic development and the central role of positive symptoms', Canadian Journal of Psychiatry, vol. 60, no. 11, pp. 515-522.
Lee, Jimmy ; Takeuchi, Hiroyoshi ; Fervaha, Gagan ; Sin, Gwen Li ; Foussias, George ; Agid, Ofer ; Farooq, Saeed ; Remington, Gary. / Subtyping schizophrenia by treatment response : Antipsychotic development and the central role of positive symptoms. In: Canadian Journal of Psychiatry. 2015 ; Vol. 60, No. 11. pp. 515-522.
@article{08e92c63619e42eaab0b551ab5d2f897,
title = "Subtyping schizophrenia by treatment response: Antipsychotic development and the central role of positive symptoms",
abstract = "We have recently proposed a model for subtyping schizophrenia based on antipsychotic (AP) treatment response. Evidence suggests that APs, both old and new, are comparable in terms of efficacy; however, one AP, clozapine, is uniquely effective in one subgroup of patients (that is, those with treatment-resistant schizophrenia [TRS]). This permits us to subdivide schizophrenia into 3 specific groups: AP responsive, clozapine responsive, and clozapine resistant. Here, we integrate this model with current criteria related to TRS and ultraresistant schizophrenia, the latter referred to in our model as clozapine resistant. We suggest several modifications to existing criteria, in line with current evidence and practice patterns, particularly emphasizing the need to focus on positive symptoms. While APs can favourably impact numerous dimensions related to schizophrenia, it is their effect on positive symptoms that distinguishes them from other psychotropics. Further, it is positive symptoms that are central to AP and clozapine resistance, and it is these people that place the greatest demands on acute and long-term inpatient resources. In moving AP development forward, we advocate specifically focusing on positive symptoms and capitalizing on the evidence we have of 3 subtypes of psychosis (that is, positive symptoms) based on treatment response, implicating 3 distinguishable forms of underlying pathophysiology. Conversely, pooling these groups risks obfuscating potentially identifiable differences. Such a position does not challenge the importance of dopamine D2 receptor blockade, but rather highlights the need to better isolate those other subgroups that require something more or entirely different.",
keywords = "Antipsychotic, Clozapine, Psychosis, Treatment-resistant, Ultraresistant",
author = "Jimmy Lee and Hiroyoshi Takeuchi and Gagan Fervaha and Sin, {Gwen Li} and George Foussias and Ofer Agid and Saeed Farooq and Gary Remington",
year = "2015",
month = "11",
day = "1",
language = "English",
volume = "60",
pages = "515--522",
journal = "Canadian Journal of Psychiatry",
issn = "0706-7437",
publisher = "Canadian Psychiatric Association",
number = "11",

}

TY - JOUR

T1 - Subtyping schizophrenia by treatment response

T2 - Antipsychotic development and the central role of positive symptoms

AU - Lee, Jimmy

AU - Takeuchi, Hiroyoshi

AU - Fervaha, Gagan

AU - Sin, Gwen Li

AU - Foussias, George

AU - Agid, Ofer

AU - Farooq, Saeed

AU - Remington, Gary

PY - 2015/11/1

Y1 - 2015/11/1

N2 - We have recently proposed a model for subtyping schizophrenia based on antipsychotic (AP) treatment response. Evidence suggests that APs, both old and new, are comparable in terms of efficacy; however, one AP, clozapine, is uniquely effective in one subgroup of patients (that is, those with treatment-resistant schizophrenia [TRS]). This permits us to subdivide schizophrenia into 3 specific groups: AP responsive, clozapine responsive, and clozapine resistant. Here, we integrate this model with current criteria related to TRS and ultraresistant schizophrenia, the latter referred to in our model as clozapine resistant. We suggest several modifications to existing criteria, in line with current evidence and practice patterns, particularly emphasizing the need to focus on positive symptoms. While APs can favourably impact numerous dimensions related to schizophrenia, it is their effect on positive symptoms that distinguishes them from other psychotropics. Further, it is positive symptoms that are central to AP and clozapine resistance, and it is these people that place the greatest demands on acute and long-term inpatient resources. In moving AP development forward, we advocate specifically focusing on positive symptoms and capitalizing on the evidence we have of 3 subtypes of psychosis (that is, positive symptoms) based on treatment response, implicating 3 distinguishable forms of underlying pathophysiology. Conversely, pooling these groups risks obfuscating potentially identifiable differences. Such a position does not challenge the importance of dopamine D2 receptor blockade, but rather highlights the need to better isolate those other subgroups that require something more or entirely different.

AB - We have recently proposed a model for subtyping schizophrenia based on antipsychotic (AP) treatment response. Evidence suggests that APs, both old and new, are comparable in terms of efficacy; however, one AP, clozapine, is uniquely effective in one subgroup of patients (that is, those with treatment-resistant schizophrenia [TRS]). This permits us to subdivide schizophrenia into 3 specific groups: AP responsive, clozapine responsive, and clozapine resistant. Here, we integrate this model with current criteria related to TRS and ultraresistant schizophrenia, the latter referred to in our model as clozapine resistant. We suggest several modifications to existing criteria, in line with current evidence and practice patterns, particularly emphasizing the need to focus on positive symptoms. While APs can favourably impact numerous dimensions related to schizophrenia, it is their effect on positive symptoms that distinguishes them from other psychotropics. Further, it is positive symptoms that are central to AP and clozapine resistance, and it is these people that place the greatest demands on acute and long-term inpatient resources. In moving AP development forward, we advocate specifically focusing on positive symptoms and capitalizing on the evidence we have of 3 subtypes of psychosis (that is, positive symptoms) based on treatment response, implicating 3 distinguishable forms of underlying pathophysiology. Conversely, pooling these groups risks obfuscating potentially identifiable differences. Such a position does not challenge the importance of dopamine D2 receptor blockade, but rather highlights the need to better isolate those other subgroups that require something more or entirely different.

KW - Antipsychotic

KW - Clozapine

KW - Psychosis

KW - Treatment-resistant

KW - Ultraresistant

UR - http://www.scopus.com/inward/record.url?scp=84946840805&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946840805&partnerID=8YFLogxK

M3 - Review article

C2 - 26720509

AN - SCOPUS:84946840805

VL - 60

SP - 515

EP - 522

JO - Canadian Journal of Psychiatry

JF - Canadian Journal of Psychiatry

SN - 0706-7437

IS - 11

ER -