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Psychopharmacology (Berl). 2012 Jan;219(1):225-33. doi: 10.1007/s00213-011-2392-3. Epub 2011 Jul 7.

Long-term (3-year) effectiveness of haloperidol, risperidone and olanzapine: results of a randomized, flexible-dose, open-label comparison in first-episode nonaffective psychosis.

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  • 1University Hospital Marqués de Valdecilla, IFIMAV, Department of Psychiatry, School of Medicine, University of Cantabria, Planta 2ª, Edificio 2 de Noviembre. Avda. Valdecilla s/n, 39008 Santander, Spain.



To enhance the effectiveness of antipsychotics in first-episode psychosis is crucial in order to achieve the most favourable prognosis. Difference in effectiveness between antipsychotics is still under debate.


The purpose of this study is to determine the long-term (3-year) effectiveness and efficacy of haloperidol, risperidone and olanzapine in first-episode schizophrenia-spectrum disorders.


This is a prospective, randomized, open-label study. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention programme of first-episode psychosis. One hundred seventy-four patients were randomly assigned to haloperidol (N = 56), olanzapine (N = 55), or risperidone (N = 63) and followed up for 3 years. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on per-protocol populations was conducted in the analysis for clinical efficacy.


The treatment discontinuation rate for any cause differed significantly between treatment groups (χ (2) = 10.752; p = 0.005), with a higher rate in haloperidol than in risperidone and olanzapine. The difference in the discontinuation rate between risperidone and olanzapine showed a tendency towards significance (χ (2) = 3.022; p = 0.082). There was a significant difference in the mean time to all-cause discontinuation between groups (log-rank χ ( 2 ) = 12.657;df = 2; p = 0.002). There were no significant advantages to any of the three treatments in reducing the psychopathology severity.


After 3 years of treatment, a lower effectiveness was observed in haloperidol compared to second-generation antipsychotics (SGAs). The use of SGAs for the treatment of early phases of nonaffective psychosis may enhance the effectiveness of antipsychotics.

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