title: An algorithm-based approach to first-episode schizophrenia: response rates over 3 prospective antipsychotic trials with a retrospective data analysis.
abstract: OBJECTIVE
  Early, effective treatment in first-episode schizophrenia is advocated, although evidence based on a systematic approach over multiple antipsychotic trials is lacking. Employing a naturalistic design, we examined response rates over 3 circumscribed antipsychotic trials.
  
  
  METHODS
  Between June 2003 and December 2008, 244 individuals with first-episode schizophrenia or schizoaffective disorder according to DSM-IV criteria were treated at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, following an algorithm that moved them through 2 antipsychotic trials, followed by a trial with clozapine. For the first 2 trials, treatment consisted of risperidone followed by olanzapine, or vice versa; each trial consisted of 3 stages (low-, full-, or high-dose) lasting up to 4 weeks at each level and adjusted according to response/tolerability. Clinical response was defined as a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved) and/or a Brief Psychiatric Rating Scale Thought Disorder subscale score ≤ 6. Data were analyzed retrospectively, and publication of anonymized clinical data was approved by the Research Ethics Board of the Centre for Addiction and Mental Health in May 2003.
  
  
  RESULTS
  In trial 1, 74.5% of individuals responded, with rates significantly higher for olanzapine (82.1%, 115/140) versus risperidone (66.3%, 69/104; P = .005). With trial 2, response rate dropped dramatically to 16.6% but again was significantly higher for olanzapine (25.7%, 9/35) compared to risperidone (4.0%, 1/25; P = .04). Response rate climbed above 70% once more, specifically 75.0% (21/28), in those individuals who agreed to a third trial with clozapine.
  
  
  CONCLUSIONS
  Results confirm a high response rate (75%) to initial antipsychotic treatment in first-episode schizophrenia. A considerably lower response rate (< 20%) occurs with a second antipsychotic trial. Results here were specific to olanzapine and risperidone, suggesting clinical differences (ie, olanzapine more effective than risperidone). A subsequent trial with clozapine is clearly warranted, although it remains unclear whether outcome would be further enhanced if it were used earlier in the treatment algorithm.
authors: Schizophrenia Program, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario, M5T 1R8, Canada. Ofer_agid@camh.net
authors: Ofer
authors: O
authors: Agid
authors: Tamara
authors: T
authors: Arenovich
authors: Gautam
authors: G
authors: Sajeev
authors: Robert B
authors: RB
authors: Zipursky
authors: Shitij
authors: S
authors: Kapur
authors: George
authors: G
authors: Foussias
authors: Gary
authors: G
authors: Remington
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D003024:Clozapine / Q000627:therapeutic use; D003987:Dibenzothiazepines / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011446:Prospective Studies; D000069348:Quetiapine Fumarate; D012189:Retrospective Studies; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine