title: Response trajectories to clozapine in a secondary analysis of pivotal trials support using treatment response to subtype schizophrenia.
abstract: OBJECTIVE
  Groups of nonrefractory patients with schizophrenia, taking antipsychotics other than clozapine, show distinct trajectories of treatment response over time. Whether similar patterns of response occur with clozapine-treated patients remains uncertain.
  
  
  METHODS
  We used a cluster analysis approach for longitudinal data (k-means longitudinal) to analyze individual patient data from 2 pivotal studies of clozapine, compared with chlorpromazine. Trajectories and symptom severity were examined in a younger, less chronic, mixed-sample (study 16, n=100) and in treatment-refractory (study 30, n=257) patients.
  
  
  RESULTS
  Early-good and delayed-partial trajectory groups were observed, with the early-good trajectory group comprised of 73/100 (73.0%) from the mixed patient study, and 147/257 (57.2%) refractory patients. In the mixed patient sample, the distribution of clozapine and chlorpromazine treatments did not differ between the early-good and delayed-partial trajectory groups; in refractory patients proportionately more clozapine treatment was present in the early-good (87/147, 59.2%), compared with the delayed-partial (35/110, 31.8%), trajectory group. In the early-good trajectory group, improvement in mean symptom severity was 63% in mixed-study patients. Clozapine resistance appeared to be present in 10/50 (20.0%) mixed-study patients, and in 35/122 (28.9%) refractory patients.
  
  
  CONCLUSIONS
  Early-good and delayed-partial response trajectories are seen in clozapine studies. The advantage of clozapine over chlorpromazine is seen most clearly in previous refractory patients, within the early-good trajectory group. Good and partial or poor responders to clozapine may merit further investigation.
authors.affiliation: Professor and Head, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia.
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
authors.affiliation: Student, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Jones
authors.affiliation: Associate Professor, Department of Psychology, Simon Fraser University, Vancouver, British Columbia.
authors.forename: Allen E
authors.initials: AE
authors.lastname: Thornton
authors.affiliation: Associate Professor, Department of Anesthesia, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia.
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Barr
authors.affiliation: Clinical Associate Professor, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia.
authors.forename: Ric M
authors.initials: RM
authors.lastname: Procyshyn
authors.affiliation: Clinical Assistant Professor, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia.
authors.forename: Fidel
authors.initials: F
authors.lastname: Vila-Rodriguez
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D002746:Chlorpromazine