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

Rationale: 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. Objective: 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. Method: 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. Results: 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. Conclusions: 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. © 2011 Springer-Verlag.
The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain under the following grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507, Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004, SENY Fundació Research Grant CI 2005–0308007 and Fundación Marqués de Valdecilla API07/011.