A Double-Blind Study of Combination of Clozapine With Risperidone in Patients With Schizophrenia: Effects on Cognition
J Clin Psychiatry 2006;67(12):1912-1919
© Copyright 2016 Physicians Postgraduate Press, Inc.
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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.
Method: 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.
Conclusion: Adjunctive treatment with
risperidone for 6 weeks in patients with
schizophrenia who had received chronic treatment with
clozapine does not significantly improve cognitive function.