Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis.
OBJECTIVE
This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia.


METHODS
This randomized trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received olanzapine (5-15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period. Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores.


RESULTS
During the treatment year, 16.1% of olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg, SD=4.24).


CONCLUSIONS
A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is warranted.
McGlashan
Thomas H
TH
Department of Psychiatry, Yale University School of Medicine, 301 Cedar St., New Haven, CT 06519, USA. thomas.mcglashan@yale.edu
Zipursky
Robert B
RB
Perkins
Diana
D
Addington
Jean
J
Miller
Tandy
T
Woods
Scott W
SW
Hawkins
Keith A
KA
Hoffman
Ralph E
RE
Preda
Adrian
A
Epstein
Irvin
I
Addington
Donald
D
Lindborg
Stacy
S
Trzaskoma
Quynh
Q
Tohen
Mauricio
M
Breier
Alan
A
D000293:Adolescent; D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009765:Obesity / Q000139:chemically induced; D000077152:Olanzapine; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy* / Q000517:prevention & control*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
D014150:Antipsychotic Agents; D010919:Placebos; D001569:Benzodiazepines; D000077152:Olanzapine