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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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Abstract

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.

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Acknowledgements

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.

Funding

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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Authors and Affiliations

  1. University 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

    Benedicto Crespo-Facorro, Rocío Pérez-Iglesias, Ignacio Mata, Obdulia Martínez-Garcia, Victor Ortiz, Jose Maria Pelayo-Terán & José Luis Vazquez-Barquero

  2. CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain

    Benedicto Crespo-Facorro, Rocío Pérez-Iglesias, Ignacio Mata, Obdulia Martínez-Garcia, Elsa Valdizan & José Luis Vazquez-Barquero

  3. Department of Physiology and Pharmacology and IBBTEC (UC-CSIC-SODERCAN), University of Cantabria, Cantabria, Spain

    Elsa Valdizan

Authors
  1. Benedicto Crespo-Facorro
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  2. Rocío Pérez-Iglesias
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  3. Ignacio Mata
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  4. Obdulia Martínez-Garcia
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  5. Victor Ortiz
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  6. Jose Maria Pelayo-Terán
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  7. Elsa Valdizan
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  8. José Luis Vazquez-Barquero
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Corresponding author

Correspondence to Benedicto Crespo-Facorro.

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Crespo-Facorro, B., Pérez-Iglesias, R., Mata, I. et al. Long-term (3-year) effectiveness of haloperidol, risperidone and olanzapine: results of a randomized, flexible-dose, open-label comparison in first-episode nonaffective psychosis. Psychopharmacology 219, 225–233 (2012). https://doi.org/10.1007/s00213-011-2392-3

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  • DOI: https://doi.org/10.1007/s00213-011-2392-3

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