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Effect of Aripiprazole on Verbal Memory and Fluency in Schizophrenic Patients

Results from the ESCAPE Study

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An Erratum to this article was published on 16 October 2012

Abstract

Background

Second-generation antipsychotics have gradually replaced first-generation antipsychotics as first-line treatment for patients with schizophrenia. Some positive effects on verbal cognition have been shown for the second-generation antipsychotics, but most studies are based on relatively small numbers of patients.

Objective

In the frame of the prospective, multi-centre, open-label study ESCAPE (A Prospective, Multicenter, Open-Label Study to Evaluate the Effectiveness and the Effect on Cognitive Function of a Treatment With Aripiprazole in a Broad Range of Schizophrenic Patients; clinicaltrials.gov identifier NCT00329810) evaluating the effectiveness and effect on cognitive functioning of aripiprazole in schizophrenic patients, we conducted a post hoc analysis to examine changes in verbal cognition and investigate the predictive value of a cognitive improvement on quality of life.

Study Design

This was a prospective, multi-centre, non-comparative, open-label study of aripiprazole in schizophrenic patients. At study enrolment, these patients were being treated with various first- or second-generation antipsychotics or were without previous antipsychotic treatment. On entering the study, all patients were treated with aripiprazole (Abilify®; Otsuka, Tokyo, Japan) monotherapy; those patients who had received prior treatment with antipsychotics had their current drug(s) tapered off over a 2-week period. A post hoc analysis of the effect of aripiprazole on two verbal cognitive measures and their correlation with efficacy measures and quality of life was conducted.

Setting

Patients with schizophrenia were recruited in 56 psychiatric hospitals.

Patients

A total of 361 patients with schizophrenia, ranging from 18 to 65 years, entered the study.

Intervention

Patients were treated with aripiprazole monotherapy at a dosage of 10–30 mg/day. Those who were receiving first- or second-generation antipsychotics at enrolment were switched to aripiprazole monotherapy by tapering off their current drug(s) over a 2-week period.

Main Outcome Measure

Physician- and patient-rated parameters were measured to gain a complete view of the effectiveness of aripiprazole on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) at baseline and at weeks 4, 8 and 12 and on the Clinical Global Impression—Severity of Illness (CGI-S) scale at baseline and at weeks 1, 2, 4, 8 and 12. A secondary endpoint of verbal cognitive function was measured by the California Verbal Learning Test (CVLT) and the Verbal Fluency (VF) test at baseline and at weeks 4 and 12. The hypothesis of an improvement in verbal cognition and its predictive value on the quality of life was formulated during data collection.

Results

238 patients completed the study. A significant improvement in verbal cognition was observed from week 4 with the long term free recall (LTFR) in the CVLT over the scheduled visits in the trial (F(2,519) = 29.67, p < 0.0001). For the phonemic (letter) subtest of the VF test, patients scored significantly better at week 12 in comparison with baseline (F(2,519) = 3.57, p = 0.0289). There was no significant effect on the semantic (categories) subtest of the VF test (F(2,518) = 0.57, p = 0.5614). Improvement in CGI-S scores at a particular moment in time predicted improvement in LTFR scores at that same moment (F(1,519) = 38.38, p < 0.0001) and in the phonemic (F(1,519) = 42.77, p < 0.0001) and semantic (F(1,518) = 67.43, p < 0.0001) subtests of the VF test. Similarly, CGI-S score improvement globally predicted quality-of-life improvement over visits. The Q-LES-Q scales leisure (F(1,144) = 14.03, p < 0.0001) and social relations (F(1,469) = 5.28, p = 0.0220) also directly correlated with verbal cognition.

Conclusion

The findings suggest that switching to, or initiating aripiprazole in schizophrenic patients results in improvement in verbal cognitive functioning. The observed improvement on quality of life is explained by the effect of aripiprazole on the CGI-S score, though the leisure and social relations scales of the Q-LES-Q also independently correlated with verbal fluency. Randomized, controlled, clinical trials of this effect of aripiprazole for selected patients are needed.

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Acknowledgments

This study was funded by Bristol-Myers Squibb Belgium. Data were obtained from the ESCAPE study (clinicaltrials.gov identifier NCT00329810), funded by Bristol-Myers Squibb Belgium and supported by Bristol-Myers Squibb Pharmaceuticals (Princeton, NJ, USA) and Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan). The funding organization did not contribute to the analysis and interpretation of the data. The funding organization did not contribute to the preparation of the paper but did contribute to the review process and the approval of the manuscript. Frank Kok, senior statistician at MSOURCE, was responsible for the data analysis in the ESCAPE study. Annick de Patoul, Veronique Halkin and Didier Pitsi are, or were employees at the time, of BMS Belgium. For all the other authors in this paper, there are no conflicts of interest to report.

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Authors and Affiliations

  1. Psychiatric Hospital Onze Lieve Vrouw, Koning Albert 1 laan 8, 8200, Brugge, Belgium

    Chris Bervoets

  2. Collaborative Antwerp Psychiatric Research Institute, Antwerp, Belgium

    Chris Bervoets, Manuel Morrens & Bernard Sabbe

  3. Psychiatric Centre Broeders Alexianen, Boechout, Belgium

    Manuel Morrens

  4. University Psychiatric Centre KU Leuven, Kortenberg, Belgium

    Kristof Vansteelandt & Joseph Peuskens

  5. MSOURCE, Vianen, The Netherlands

    Frank Kok

  6. Bristol-Myers Squibb SA, Braine-l’Alleud, Belgium

    Annick de Patoul, Veronique Halkin & Didier Pitsi

  7. Cliniques Universitaires Saint Luc, Brussels, Belgium

    Eric Constant

  8. Psychiatric Hospital Sint Norbertus, Duffel, Belgium

    Bernard Sabbe

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  1. Chris Bervoets
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  2. Manuel Morrens
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Correspondence to Chris Bervoets.

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Bervoets, C., Morrens, M., Vansteelandt, K. et al. Effect of Aripiprazole on Verbal Memory and Fluency in Schizophrenic Patients. CNS Drugs 26, 975–982 (2012). https://doi.org/10.1007/s40263-012-0003-4

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