A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.
BACKGROUND
Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy.


METHODS
This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003.


RESULTS
Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group.


CONCLUSIONS
Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.
Akdede
Berna Binnur Kivircik
BB
Department of Psychiatry, Dokuz Eylül University School of Medicine, Izmir, Turkey. binnur.kivircik@deu.edu.tr
Anil Yağcioğlu
A Elif
AE
Alptekin
Köksal
K
Turgut
Tolga I
TI
Tümüklü
Mevhibe
M
Yazici
M Kâzim
MK
Jayathilake
Karu
K
Tunca
Zeliha
Z
Göğüş
Ahmet
A
Meltzer
Herbert Y
HY
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001288:Attention; D003024:Clozapine / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003024:Clozapine; D018967:Risperidone