Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome.
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.
Woods
Scott W
SW
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA.
Breier
Alan
A
Zipursky
Robert B
RB
Perkins
Diana O
DO
Addington
Jean
J
Miller
Tandy J
TJ
Hawkins
Keith A
KA
Marquez
Eva
E
Lindborg
Stacy R
SR
Tohen
Mauricio
M
McGlashan
Thomas H
TH
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
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine