Long-term (3-year) neurocognitive effectiveness of antipsychotic medications in first-episode non-affective psychosis: a randomized comparison of haloperidol, olanzapine, and risperidone
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The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate.
A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis.
Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis.
The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.
KeywordsSchizophrenia Neurocognition Antipsychotic treatments
The present study was performed at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Instituto de Salud Carlos III PI020499, PI050427; 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. We wish to thank the PAFIP researchers who helped with data collection and specially acknowledge César González-Blanch and Mrs. Gema Pardo for data collection and their research assistance. In addition, we acknowledge the participants and their families for enrolling in this study.
Conflict of Interest
Prof. Vazquez-Barquero and Prof. Crespo-Facorro have received unrestricted research funding from AstraZeneca, Pfizer, Bristol-Myers Squibb, and Johnson & Johnson that were 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. Prof. Tabarés-Seisdedos has received grants from or acted as a consultant for the following companies: AstraZeneca, Janssen, Eli Lilly, Lundbeck, Novartis, Pfizer, Sanofi-Aventis, and Wyeth that were deposited into research accounts at the University of Valencia. The remaining authors report no competing interests.
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