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.
authors.affiliation: Consultant, Department of General Psychiatry, Institute of Mental Health, Singapore, Singapore; Assistant Professor, Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore; Clinical Fellow, Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lee
authors.affiliation: Postdoctoral Fellow, Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario; Collaborative Researcher, Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Student, Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario; Student, Institute of Medical Science, University of Toronto, Toronto, Ontario.
authors.forename: Gagan
authors.initials: G
authors.lastname: Fervaha
authors.affiliation: Consultant, Department of Psychiatry, Singapore General Hospital, Singapore, Singapore.
authors.forename: Gwen Li
authors.initials: GL
authors.lastname: Sin
authors.affiliation: Staff Psychiatrist, Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario; Assistant Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario.
authors.forename: George
authors.initials: G
authors.lastname: Foussias
authors.affiliation: Staff Psychiatrist, Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario; Assistant Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario.
authors.forename: Ofer
authors.initials: O
authors.lastname: Agid
authors.affiliation: Professor, Department of Psychiatry, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, Pakistan; Visiting Professor, Centre for Ageing and Mental Health, Staffordshire University, Staffordshire, England.
authors.forename: Saeed
authors.initials: S
authors.lastname: Farooq
authors.affiliation: Lead, Subspecialty Clinics, Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario; Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D006801:Humans; D012559:Schizophrenia / Q000145:classification / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine