title: Long-term (3-year) neurocognitive effectiveness of antipsychotic medications in first-episode non-affective psychosis: a randomized comparison of haloperidol, olanzapine, and risperidone.
abstract: BACKGROUND
  The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Psychiatry, Marqués de Valdecilla University Hospital, IFIMAV, School of Medicine, University of Cantabria, Avda. Valdecilla s/n, 39008 Santander, Spain. rayesa@humv.es
authors: Rosa
authors: R
authors: Ayesa-Arriola
authors: Jose Manuel
authors: JM
authors: Rodríguez-Sánchez
authors: Rocío
authors: R
authors: Pérez-Iglesias
authors: Roberto
authors: R
authors: Roiz-Santiáñez
authors: Obdulia
authors: O
authors: Martínez-García
authors: Jose
authors: J
authors: Sánchez-Moreno
authors: Rafael
authors: R
authors: Tabarés-Seisdedos
authors: Jose L
authors: JL
authors: Vázquez-Barquero
authors: Benedicto
authors: B
authors: Crespo-Facorro
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D000077152:Olanzapine; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000503:physiopathology; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine