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Psychiatry Res. 2017 Dec;258:153-157. doi: 10.1016/j.psychres.2017.10.010. Epub 2017 Oct 3.

Plasma ratio of clozapine to N-desmethylclozapine can predict cognitive performance in treatment-resistant psychotic patients.

Author information

1
Hospital de la Santa Creu i Sant Pau, Department of Psychiatry, Barcelona, Spain.
2
Sant Pau Institute of Biomedical Research IIB-Sant Pau, Department of Psychiatry, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain. Electronic address: mcarceller@santpau.cat.
3
Hospital de la Santa Creu i Sant Pau, Department of Psychiatry, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
4
Sant Pau Institute of Biomedical Research IIB-Sant Pau, Department of Psychiatry, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.

Abstract

Cognitive symptoms play a central role in schizophrenia and are strongly associated with social functioning. Treatment with clozapine presents controversial results regarding its effects on cognition. The opposite effects of clozapine and n-desmethylclozapine (NDMC) on cholinergic system have been suggested to underlie these inconclusive findings. The aim of this study is to determine whether clozapine/NDMC ratio can predict cognitive performance in patients with treatment-resistant psychosis. Nineteen clinically stable patients with schizophrenia or schizoaffective disorder treated with clozapine monotherapy completed demographic and clinical interviews. For the purpose of the study, patients were assessed with a neuropsychological battery and on the same day a blood sampling was obtained from each patient to measure plasma levels of clozapine and NDMC. Our results showed that clozapine/NDMC ratio, but not clozapine or NDMC plasma levels separately, was a predictive factor of cognitive performance, specifically of executive functioning. Our results showed that lower clozapine/NDMC ratios are associated with better executive functioning in clinically stable patients. These findings could be interpreted by the different pharmacodynamic properties on cholinergic, dopaminergic and serotonergic systems of NDMC compared to clozapine.

KEYWORDS:

Cognition; Executive functioning; Neurocognition; Norclozapine; Schizophrenia; Treatment-resistant psychosis; Treatment-resistant schizophrenia

PMID:
29024893
DOI:
10.1016/j.psychres.2017.10.010
[Indexed for MEDLINE]

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