Neuropsychological effects of maintenance treatment with Clozapine in treatment-resistant psychotic disorder

Introduction. Clozapine is a second-generation antipsychotic drug that is mainly prescribed for treatment-resistant psychotic disorder. It is known to have several undesirable side effects, including cognitive functional complaints, such as memory or attention. The aim of this work is to study if reduction of the dosage within the therapeutic margins could improve cognitive performance of Clozapine treated patients. To do so, a study was made of the relationship between Clozapine plasma levels and neuropsychological performance in patients undergoing Clozapine monotherapy. Material and Methods. This is a single-blind design study of the correlation between Clozapine plasma levels and neuropsychological testing in a sample of 19 patients with treatment-resistant psychotic disorder in whom Clozapine was the only psychotropic drug. Spearman correlations were carried out between neuropsychological variables and Clozapine plasma levels. Additionally, the sample was divided into two groups between patients with high Clozapine plasma drug levels (Clz pl≥300μg/L) and low ones (Clz pl<300μg/L). MANOVA was performed to determine neuropsychological differences between the two groups. Subsequently, a linear regression model was carried out to predict neuropsychological performance. Results. There was no significant Spearman correlation between neuropsychological scores and Clozapine plasma levels (p>0.1). MANOVA showed no significant differences between the two groups in any of the tests administered, although there was a trend towards significance in the number on attempts of the Card Sorting Test (WCST), where subjects with high levels of Clozapine showed worse performance (F=3.86; df=1.17; p=0.07).The linear regression model showed that only plasma levels significantly predicted executive performance, explaining 31% of the variance (F=3.62; df=2.16; p=0.05). Conclusion. No relationship between plasma levels of Clozapine and cognitive performance has been found. This result suggests that it is not desirable to reduce a relevant dose of Clozapine in patients with cognitive complaints.