Relationship between serum clozapine to N-desmethyclozapine ratio and cognitive performance among people with treatment-resistant schizophrenia

Objective We evaluated the relationship of serum clozapine and N-desmethyl clozapine (NDMC) and their ratio and cognition among people with treatment-resistant schizophrenia (TRS), an area that has been sub-optimally researched. Methods Cognitive function and serum clozapine and NDMC levels of 91 patients who were treated with clozapine were collected retrospectively. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to measure cognition. Associations between the variables were assessed using Pearson’s correlation coefficients and multivariable linear regression models were constructed to determine whether serum clozapine, NDMC, or their ratio independently predicted cognition. Results The mean age of the 91 participants was 33.8 (±10.3), and 70% were males. While cognitive deficits (CD) were prominent among the participants, the associations between the BACS z-scores and serum clozapine, NDMC, and their ratio were weak in magnitude. There was no evidence of a significant independent association between serum clozapine level ( p = .3380, norclozapine level ( p = .277), or their ratio ( p = .909) and the BACS composite score. Conclusion The lack of significant association between the serum clozapine to NDMC ratio observed in our and other studies suggest that severity of the illness and other clinical factors are likely to override any pro-cognitive effect of NDMC in TRS.