title: Effects of atypical antipsychotics on the syndromal profile in treatment-resistant schizophrenia.
abstract: BACKGROUND
  There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics. We are exploring whether this expanded clinical efficacy can also be seen in patients with treatment-resistant schizophrenia.
  
  
  METHODS
  The subjects were 157 treatment-resistant inpatients diagnosed with DSM-IV schizophrenia or schizoaffective disorder. They were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol in a 14-week double-blind trial and rated with a standard measure of clinical antipsychotic efficacy (Positive and Negative Syndrome Scale [PANSS]). Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined. Data were gathered from June 1996 to December 1999.
  
  
  RESULTS
  The underlying PANSS factor structure, as indicated by the factor loadings, was essentially identical at baseline and endpoint. At baseline, the excitement factor was followed by the positive, negative, cognitive, and depression/anxiety factors, explaining 49.4% of the total variance. At endpoint, the positive factor was followed by the negative, excitement, cognitive, and depression/anxiety factors, explaining 55.5% of the total variance. The endpoint data indicated statistically significant (p <.05) improvements over time on the positive factor for all 3 atypicals, but not for haloperidol. The negative factor showed significant improvement for clozapine and olanzapine, with significant worsening for haloperidol. Clozapine, olanzapine, and risperidone were superior to haloperidol on the negative factor, while clozapine was also superior to risperidone. The cognitive factor showed significant improvement for all atypicals, as did the depression/anxiety factor. Only clozapine showed improvement on the excitement factor and was superior to both haloperidol and risperidone.
  
  
  CONCLUSIONS
  Treatment with atypical antipsychotics did not substantially change the underlying PANSS 5-factor structure. However, antipsychotic treatment with all 3 atypical medications was associated with significant improvements on 3 of 5 syndromal domains (positive, cognitive, and depression/anxiety) of schizophrenia. Clozapine and olanzapine also showed improvement on the negative factor. Only clozapine was associated with improvement on the excitement domain. This finding confirms that atypicals are associated with improvement of an expanded spectrum of symptoms in treatment-resistant patients.
authors.affiliation: Nathan Kline Institute, Orangeburg, N.Y. , USA. lindenmayer@nki.rfmh.org
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lindenmayer
authors.forename: Pal
authors.initials: P
authors.lastname: Czobor
authors.forename: Jan
authors.initials: J
authors.lastname: Volavka
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.forename: Brian
authors.initials: B
authors.lastname: Sheitman
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McEvoy
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Cooper
authors.forename: Miranda
authors.initials: M
authors.lastname: Chakos
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D003024:Clozapine / Q000627:therapeutic use; D004311:Double-Blind Method; D005163:Factor Analysis, Statistical; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine