Clozapine and global cognition in schizophrenia

Tarek K. Rajji, Hiroyuki Uchida, Zahinoor Ismail, Wenzie Ng, David C. Mamo, Gary Remington, Bruce G. Pollock, Benoit H. Mulsant

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)431-436
Number of pages6
JournalJournal of Clinical Psychopharmacology
Volume30
Issue number4
DOIs
Publication statusPublished - 2010

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norclozapine
Clozapine
Cognition
Schizophrenia

Keywords

  • clozapine
  • cognition
  • muscarinic
  • N-desmethylclozapine
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Medicine(all)

Cite this

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. https://doi.org/10.1097/JCP.0b013e3181e69060

Clozapine and global cognition in schizophrenia. / Rajji, Tarek K.; Uchida, Hiroyuki; Ismail, Zahinoor; Ng, Wenzie; Mamo, David C.; Remington, Gary; Pollock, Bruce G.; Mulsant, Benoit H.

In: Journal of Clinical Psychopharmacology, Vol. 30, No. 4, 2010, p. 431-436.

Research output: Contribution to journalArticle

Rajji, TK, Uchida, H, Ismail, Z, Ng, W, Mamo, DC, Remington, G, Pollock, BG & Mulsant, BH 2010, 'Clozapine and global cognition in schizophrenia', Journal of Clinical Psychopharmacology, vol. 30, no. 4, pp. 431-436. https://doi.org/10.1097/JCP.0b013e3181e69060
Rajji, Tarek K. ; Uchida, Hiroyuki ; Ismail, Zahinoor ; Ng, Wenzie ; Mamo, David C. ; Remington, Gary ; Pollock, Bruce G. ; Mulsant, Benoit H. / Clozapine and global cognition in schizophrenia. In: Journal of Clinical Psychopharmacology. 2010 ; Vol. 30, No. 4. pp. 431-436.
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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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T1 - Clozapine and global cognition in schizophrenia

AU - Rajji, Tarek K.

AU - Uchida, Hiroyuki

AU - Ismail, Zahinoor

AU - Ng, Wenzie

AU - Mamo, David C.

AU - Remington, Gary

AU - Pollock, Bruce G.

AU - Mulsant, Benoit H.

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N2 - 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.

AB - 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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