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Title: Clozapine and global cognition in schizophrenia
Authors: Rajji, Tarek K.
Uchida, Hiroyuki
Ismail, Zahinoor
Ng, Wenzie
Mamo, David
Remington, Gary
Pollock, Bruce G.
Mulsant, Benoit H.
Keywords: Clozapine
Cognition -- Data processing
Muscarinic receptors
Issue Date: 2010
Publisher: Lippincott Williams & Wilkins
Citation: Rajji, T. K., Uchida, H., Ismail, Z., Ng, W., Mamo, D. C., Remington, G., ... & Mulsant, B. H. (2010). Clozapine and global cognition in schizophrenia. Journal of Clinical Psychopharmacology, 30(4), 431-436.
Abstract: Objective: Clozapine (CLZ) has been shown to have a beneficial effect on cognition in schizophrenia in some studies and a detrimental effect in others. The relative effect and exposure to CLZ and its major metabolite-N-desmethylclozapine (NDMC)-could explain these discrepancies. Methods: Using a validated measure of global cognition, we performed 2 binary logistic regression models to assess the relationship among cognition, age, sex, CLZ dose, CLZ and NDMC plasma levels, and their ratio (CLZ/NDMC) in individuals with schizophrenia spectrum disorders. Model 1 included age, sex, CLZ dose, and CLZ and NDMC levels. Model 2 included age, sex, CLZ dose, and CLZ/NDMC. Results: Among 73 subjects (mean [SD] age, 41.6 [12.0] years), 16 (21.9%) had high cognitive impairment, whereas the rest had low cognitive. In model 1, age and CLZ level were associated with high cognitive impairment (odds ratio [95% confidence interval] for age, 1.079 [1.011-1.152]; CLZ level, 1.010 [1.003-1.017]), whereas NDMC level was associated with its absence (NDMC level, 0.987 [0.977-0.997]). In model 2, age, male sex, and CLZ/NDMC were associated with cognitive impairment (age, 1.083 [1.015-1.154]; sex, 0.178 [0.032-0.994]; CLZ/NDMC, 7.302 [1.823-29.253]). Clozapine dose was not associated with cognition in either model. Conclusions: After controlling for age, sex, and dose, CLZ/NDMC was more strongly associated with cognition than CLZ or NDMC levels. N-desmethylclozapine agonist activity versus CLZ antagonist activity at the muscarinic receptors could explain the strength of the association of CLZ/NDMC with cognition.
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