© Georg Thieme Verlag KG Stuttgart · New York
Effect of Aripiprazole on Cognition in the Treatment of Patients with Schizophrenia
10 December 2009 (eFirst)
Background: The aim of this study was to assess the cognitive effects of aripiprazole in inpatients with schizophrenia.
Methods: This was an investigator-initiated, open label eight-week trial evaluating 56 inpatients with the DSM-IV diagnosis of schizophrenia. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and tolerability was assessed each week using the Udvalg for Klinske Undersogelser side effect rating scale (UKU). Cognitive function was assessed at baseline, week 4 and week 8.
Results: Aripiprazole showed significant improvement in PANSS total score and all subscores between baseline and endpoint visit. The substance was very well tolerated. Patients improved significantly in verbal memory, reaction time and reaction quality/attention from baseline to week eight. Furthermore, mean z-values of individual cognitive domains summarized in a global cognitive index improved significantly from baseline to week eight.
Discussion: Our results suggest that aripiprazole provides a valuable treatment option for patients with schizophrenia.
- 1 Akdede BB, nil Yagcioglu AE, Alptekin K. et al . A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition. J Clin Psychiatry. 2006; 67 1912-1919
American Psychiatric Association
Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Washington DC 1994
- 3 Andersen B. Regression toward the mean.
In: Methodological errors in medical research.Blackwell Scientific Publications, London 1990 pp 98-108
- 4 Beasley CM, Tollefson G, Tran P. et al . Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology. 1996; 14 111-123
- 5 Bilder RM, Goldman RS, Volavka J. et al . Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Am J Psychiatry. 2002; 159 1018-1028
- 6 Bilder RM, Reiter G, Bates J. et al . Cognitive development in schizophrenia: follow-back from the first episode. J Clin Exp Neuropsychol. 2006; 28 270-282
- 7 Burris KD, Molski TF, Xu C. et al . Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther. 2002; 302 381-389
- 8 Cording C. Conceptual aspects in development and implementation of basic psychiatric documentation. Psychiatr Prax. 1998; 25 175-178
- 9 Davidson M, Galderisi S, Weiser M. et al . Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). Am J Psychiatry. 2009; 166 675-682
- 10 Dossenbach M, rango-Davila C, Silva IH. et al . Response and relapse in patients with schizophrenia treated with olanzapine, risperidone, quetiapine, or haloperidol: 12-month follow-up of the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study. J Clin Psychiatry. 2005; 66 1021-1030
- 11 Fujii DE, Wylie AM, Nathan JH. Neurocognition and long-term prediction of quality of life in outpatients with severe and persistent mental illness. Schizophr Res. 2004; 69 67-73
- 12 Gold JM, Carpenter C, Randolph C. et al . Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia. Arch Gen Psychiatry. 1997; 54 159-165
- 13 Goldberg TE, Goldman RS, Burdick KE. et al . Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect?. Arch Gen Psychiatry. 2007; 64 1115-1122
- 14 Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia?. Am J Psychiatry. 1996; 153 321-330
- 15 Gutbrod K, Cohen R, Mager B. et al . Coding and recall of categorized material in aphasics. J Clin Exp Neuropsychol. 1989; 11 821-841
- 16 Guy W.
Clinical Global Impressions. ECDEU Assessment Manual for Psychopharmacology National Institute of Mental Health, Rockville, MD revised 1976
- 17 Harvey PD. Ziprasidone and cognition: the evolving story. J Clin Psychiatry. 2003; 64 ((Suppl 19)) 33-39
- 18 Hawkins KA. Memory deficits in patients with schizophrenia: preliminary data from the Wechsler Memory Scale-Third Edition support earlier findings.
J Psychiatry Neurosci. 1999 24: 341-347
- 19 Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology. 1998; 12 426-445
- 20 Ichikawa J, Dai J, O IA. et al . Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum. Neuropsychopharmacology. 2002; 26 325-339
- 21 Keefe RS, Bilder RM, Davis SM. et al . Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry. 2007; 64 633-647
- 22 Kay SR, Opler LA, Lindenmayer JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res. 1998; 23 99-110
- 23 Keefe RS, Roitman SE, Harvey PD. et al . A pen-and-paper human analogue of a monkey prefrontal cortex activation task: spatial working memory in patients with schizophrenia. Schizophr Res. 1995; 17 25-33
- 24 Keefe RS, Silva SG, Perkins DO. et al . The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull. 1999; 25 201-222
- 25 Keefe RS, Sweeney JA, Gu H. et al . Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double-blind 52-week comparison. Am J Psychiatry. 2007; 164 1061-1071
- 26 Kern RS, Green MF, Cornblatt BA. et al . The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine. Psychopharmacology (Berl). 2006; 187 312-320
- 27 Lindenmayer JP, Khan A, Iskander A. et al . A randomized controlled trial of olanzapine versus haloperidol in the treatment of primary negative symptoms and neurocognitive deficits in schizophrenia. J Clin Psychiatry. 2007; 68 368-379
- 28 Lingjaerde O, Ahlfors UG, Bech P. et al . The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl. 1987; 334 1-100
- 29 Millan MJ. Improving the treatment of schizophrenia: focus on serotonin (5-HT)(1A) receptors. J Pharmacol Exp Ther. 2000; 295 853-861
- 30 Milev P, Ho BC, Arndt S. et al . Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. Am J Psychiatry. 2005; 162 495-506
- 31 Purdon SE, Jones BD, Stip E. et al . The Canadian Collaborative Group for research in schizophrenia Arch Gen Psychiatry. 2000; 57 249-258
R Development Core Team
A language and environment for statistical computing. Foundation for Statistical Computing, Vienna, Austria 2008
- 33 Reitan RM. Validity of the trailmaking test as an indication of organic brain damage. Percept Mot Skills. 1958; 8 271-276
- 34 Rey A.
Lexamen clinique en psychologie. Presse Universitaire de France, Paris 1958
- 35 Riedel M, Muller N, Spellmann I. et al . Efficacy of olanzapine versus quetiapine on cognitive dysfunctions in patients with an acute episode of schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2007; 257 402-412
- 36 Riedel M, Spellmann I, Strassnig M. et al . Effects of risperidone and quetiapine on cognition in patients with schizophrenia and predominantly negative symptoms. Eur Arch Psychiatry Clin Neurosci. 2007; 257 360-370
- 37 Saykin AJ, Gur RC, Gur RE. et al . Neuropsychological function in schizophrenia. Selective impairment in memory and learning. Arch Gen Psychiatry. 1991; 48 618-624
- 38 Spreen O, Benton AL. Comparative studies of some psychological tests for cerebral damage. J Nerv Ment Dis. 1965; 140 323-333
- 39 Stahl SM. Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, part 1, “Goldilocks” actions at dopamine receptors. J Clin Psychiatry. 2001; 62 841-842
- 40 Stahl SM. Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, part 2: illustrating their mechanism of action. J Clin Psychiatry. 2001; 62 923-924
- 41 Tabares-Seisdedos R, Balanza-Martinez V, Sanchez-Moreno J. et al . Neurocognitive and clinical predictors of functional outcome in patients with schizophrenia and bipolar I disorder at one-year follow-up. J Affect Disord. 2008; 109 286-299
- 42 Wiebel B, Happe A, Peikara F.
Das neuropsychologische Diagnostikprogramm TESTBAT. Psymed, Dulmen 1995
- 43 Wittorf A, Sickinger S, Wiedemann G. et al . Neurocognitive effects of atypical and conventional antipsychotic drugs in schizophrenia: a naturalistic 6-month follow-up study. Arch Clin Neuropsychol. 2008; 23 271-282
- 44 Woodward ND, Purdon SE, Meltzer HY. et al . (2005) A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia. Int J Neuropsychopharmacol. 2005; 8 457-472
R. Schennach-Wolff, MD
Department of Psychiatry
Phone: +49/89/5160 58 69
Fax: +49/89/5160 58 57