title: Time course of improvement with antipsychotic medication in treatment-resistant schizophrenia.
abstract: BACKGROUND
  Improvements are greatest in the earlier weeks of antipsychotic treatment of patients with non-resistant schizophrenia.
  
  
  OBJECTIVE
  To address the early time-line for improvement with antipsychotics in treatment-resistant schizophrenia.
  
  
  METHODS
  Randomised double-blind trials of antipsychotic medication in adult patients with treatment-resistant schizophrenia were investigated (last search June 2010). A series of metaregression analyses were carried out to examine the effect of time on the average item scores in the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) at three or more distinct time points within the first 6 weeks of treatment.
  
  
  RESULTS
  Study duration varied from 4 weeks to 1 year and the definitions of treatment resistance as well as of treatment response were not necessarily consistent across 19 identified studies, resulting in highly variable rates of response (0–76%).The mean standardised baseline item score in the PANSS or BPRS was 3.4 (s.e. = 0.06) in the five studies included in the meta-regression analysis, with the average baseline Clinical Global Impression – Severity score being 5.2 (marked illness). For the pooled population treated with a range of antipsychotics (n = 1019), significant reductions in the mean item scores occurred during the first 4 weeks; improvements observed in later weeks were smaller and non-significant. In contrast, weekly improvement with clozapine was significant throughout (n = 356).
  
  
  CONCLUSIONS
  Our findings provide preliminary evidence that the majority of improvement with antipsychotics may occur relatively early.More consistent improvements with clozapine may be associated with a gradual titration. To further elucidate response patterns, future studies are needed to provide data over regular intervals during earlier stages of treatment.
authors.affiliation: Centre for Addiction and Mental Health, Geriatric Mental Health Program and Multimodal Imaging Group, and Department of Psychiatry, University of Toronto, Ontario, Canada, and Keio University School of Medicine, Department of Neuropsychiatry, Tokyo, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.forename: Tamara
authors.initials: T
authors.lastname: Arenovich
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.forename: Ofer
authors.initials: O
authors.lastname: Agid
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D015233:Models, Statistical; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine