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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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 (χ2 = 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 (χ2 = 3.022; p = 0.082). There was a significant difference in the mean time to all-cause discontinuation between groups (log-rank χ2 = 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.
KeywordsAntipsychotics Schizophrenia Treatment Efficacy Clinical practice
We wish to thank the PAFIP researchers who helped with data collection and specially acknowledge Mrs. Gema Pardo for data collection. Finally, we would also like to thank the participants and their families for enrolling in this study.
Conflict of interest disclosures
Prof. Vazquez-Barquero and Prof. Crespo-Facorro have received unrestricted research funding from AstraZeneca, Pfizer, Bristol-Myers Squibb and Johnson & Johnson that was deposited into research accounts at the University of Cantabria. Prof. Vazquez-Barquero has received honoraria for his participation as a speaker at educational events from Johnson & Johnson. Prof. Crespo-Facorro has received honoraria for his participation as a speaker at educational events from Pfizer, Bristol-Myers Squibb and Johnson & Johnson and consultant fees from Pfizer. Dr. Mata has received honoraria for his participation as a speaker at educational events from Johnson & Johnson. Dr. Perez-Iglesias has received support to attend conferences from Lilly. Drs. Pelayo-Teran and Valdizan, Mrs. Martinez and Mr. Ortiz report no additional financial or other relationship relevant to the subject of this article.
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.
No pharmaceutical company supplied any financial support towards it. The study, designed and directed by B C-F and JL V-B, conformed to international standards for research ethics and was approved by the local institutional review board.
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