title: Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome.
abstract: BACKGROUND
  The prodromal phase of schizophrenic disorders has been described prospectively. The present study aimed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo.
  
  
  METHODS
  This was a double-blind, randomized, parallel-groups, placebo-controlled trial with fixed-flexible dosing conducted at four sites. Sixty patients met prodromal diagnostic criteria, including attenuated psychotic symptoms, as determined by structured interviews. Olanzapine 5-15 mg daily or placebo was prescribed for 8 weeks.
  
  
  RESULTS
  In the mixed-effects, repeated-measures analysis, the treatment x time interaction for the change from baseline on the Scale of Prodromal Symptoms total score was statistically significant, and post hoc analyses revealed that the olanzapine-placebo difference reached p<.10 by week 6 and p<.05 at week 8. Ratings of extrapyramidal symptoms remained low in each group and were not significantly different. Olanzapine patients gained 9.9 lb versus.7 lb for placebo patients (p<.001).
  
  
  CONCLUSIONS
  This short-term analysis suggests olanzapine is associated with significantly greater symptomatic improvement but significantly greater weight gain than is placebo in prodromal patients. Extrapyramidal symptoms with olanzapine were minimal and similar to those with placebo. Future research over the longer term with more patients will be needed before recommendations can be made regarding routine treatment.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Woods
authors.forename: Alan
authors.initials: A
authors.lastname: Breier
authors.forename: Robert B
authors.initials: RB
authors.lastname: Zipursky
authors.forename: Diana O
authors.initials: DO
authors.lastname: Perkins
authors.forename: Jean
authors.initials: J
authors.lastname: Addington
authors.forename: Tandy J
authors.initials: TJ
authors.lastname: Miller
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hawkins
authors.forename: Eva
authors.initials: E
authors.lastname: Marquez
authors.forename: Stacy R
authors.initials: SR
authors.lastname: Lindborg
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
authors.forename: Thomas H
authors.initials: TH
authors.lastname: McGlashan
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine