Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
American Journal of Psychiatry (Impact Factor: 12.3). 06/2006; 163(5):790-9. DOI: 10.1176/appi.ajp.163.5.790
Source: PubMed


This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia.
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.
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).
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.

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    • "For those at the highest end of the risk spectrum, early commencement of preventive treatments may win time in combatting the pathophysiological processes associated with psychosis onset (de Koning et al. 2009; Pasternak et al. 2012). In contrast, for those in the low-risk group, reliable risk estimation will prevent the potentially stigmatizing consequences of a psychiatric diagnosis and exposure to potentially harmful effects of pharmacological and other interventions (McGlashan et al. 2006). Clinical assessments alone for determination of transition risk to psychosis are problematic due to the fluctuating course of symptoms in high-risk individuals (Ruhrmann et al. 2010a). "
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    • "In North America, the Prevention through Risk Identification Management and Education (PRIME) study compared the transition rates of a 12-month treatment with olanzapine (5–15 mg daily) or placebo.66 At the end of the treatment phase, 16% of the UHR individuals treated with olanzapine and 38% of the placebo group converted to psychosis, but the difference between transition rates did not reach statistical significance.66 "
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    • "Recent controlled studies using antipsychotics have demonstrated a decrease of the conversion rate,3,4) but most researchers and clinicians still hesitate to prescribe drugs for ARMS due to ethical considerations such as the risk of false-positive identification of ARMS and the adverse reactions related to pharmacotherapy. In fact, antipsychotics are often associated with adverse effects that are undesirable for young people, such as pronounced weight gain and sexual dysfunction.3,5) "
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