Abstract
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. 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. 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 associate...Continue Reading
References
Jan 3, 1991·European Journal of Pharmacology·C BoldenE Richelson
Jan 1, 1988·Psychopharmacology·U Bondesson, L H Lindström
Apr 12, 1974·Nature·R J Miller, C R Hiley
Jul 1, 1974·Archives of General Psychiatry·S SnyderH I Yamamura
Dec 1, 1994·Biological Psychiatry·R W BuchananA Breier
Nov 1, 1994·Journal of the American Geriatrics Society·S L HartmaierG G Koch
Sep 1, 1994·Schizophrenia Research·T P ZahnR J Haier
Jul 1, 1994·Journal of Gerontology·J N MorrisL A Lipsitz
Nov 15, 1993·Biological Psychiatry·C HaggerH Y Meltzer
Apr 15, 1993·European Journal of Pharmacology·M KuoppamäkiJ Hietala
Jan 1, 1993·The British Journal of Psychiatry : the Journal of Mental Science·T E GoldbergD R Weinberger
Oct 1, 1996·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·A L HoffJ G Csernansky
Jan 1, 1996·Psychiatric Services : a Journal of the American Psychiatric Association·J GraceS Gunn
Mar 1, 1997·Pharmacopsychiatry·A Meyer-LindenbergB Gallhofer
Apr 1, 1997·The Journal of Neuropsychiatry and Clinical Neurosciences·D E FujiiJ M Compton
Feb 12, 1998·British Journal of Clinical Pharmacology·B EiermannL Bertilsson
Jul 23, 1998·Neuropsychology·R W Heinrichs, K K Zakzanis
Nov 18, 1998·The Journal of Clinical Psychiatry·J P LindenmayerD Allen
May 5, 1999·Schizophrenia Research·M A LeeH Y Meltzer
Feb 7, 2001·Schizophrenia Bulletin·M F GreenJ Mintz
Mar 30, 2001·Schizophrenia Research·S E PurdonL Boulay
Apr 3, 2001·The American Journal of Psychiatry·M ChakosB Sheitman
Aug 16, 2001·Journal of Clinical Pharmacology·O V Olesen, K Linnet
Jan 7, 2003·Archives of General Psychiatry·Herbert Y MeltzerUNKNOWN International Suicide Prevention Trial Study Group
Jul 8, 2003·Psychopharmacology·Tonmoy SharmaVeena Kumari
Nov 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Cyrille SurP Jeffrey Conn
Dec 4, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Frank P BymasterDavid L Mckinzie
Jul 20, 2004·Psychopharmacology·D M WeinerM R Brann
Mar 15, 2005·Psychopharmacology·Marilyn A DaviesBryan L Roth
May 19, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Zhu LiHerbert Y Meltzer
Sep 2, 2005·The Journal of Pharmacology and Experimental Therapeutics·E S BursteinM R Brann
Aug 25, 2006·Schizophrenia Research·Marci L ChewGeorges Gharabawi
Oct 19, 2006·Biological Psychiatry·Houman Homayoun, Bita Moghaddam
Dec 14, 2007·Schizophrenia Research·Philip D HarveyAntony D Loebel
Feb 1, 2008·The Journal of Clinical Psychiatry·Herbert Y MeltzerJoyce G Small
Sep 17, 2008·Journal of Clinical Psychopharmacology·Menahem I KrakowskiKaren A Nolan
Citations
Mar 12, 2011·Psychopharmacology·Adrian Newman-Tancredi, Mark S Kleven
Dec 18, 2013·Drugs & Aging·Delia Bishara, David Taylor
Jun 4, 2011·Expert Opinion on Drug Safety·Philip Gerretsen, Bruce G Pollock
Mar 23, 2011·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Zahinoor IsmailRobert R Bies
Dec 8, 2010·Brain Research Bulletin·Aygün ErtuğrulEsen Saka
May 4, 2011·Acta Psychiatrica Scandinavica·J NielsenD Taylor
Sep 4, 2015·Journal of Clinical and Experimental Neuropsychology·Rachel BattySusan Rossell
Jul 19, 2012·Expert Opinion on Pharmacotherapy·Eric Fakra, Jean-Michel Azorin
Jun 1, 2011·Schizophrenia Research·Chisa TsutsumiShitij Kapur
Jan 25, 2011·Neuroscience Letters·Mariana PedriniClarissa Severino Gama
May 30, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·H OzdemirE Saka
Apr 11, 2018·Genes, Brain, and Behavior·B WulaerK Yamada
May 11, 2019·Expert Review of Clinical Pharmacology·Georgios SchoretsanitisJose de Leon
Nov 27, 2019·Expert Opinion on Drug Safety·Kenya A Costa-DookhanMargaret K Hahn
Mar 15, 2018·Der Nervenarzt·P RiedelM Bauer
Nov 5, 2020·Journal of Psychopharmacology·Farhana IslamTarek K Rajji
Nov 18, 2020·Psychiatry Investigation·Royun ParkEuitae Kim
Jan 23, 2021·Scientific Reports·Kenya A Costa-DookhanMargaret K Hahn
Jul 1, 2020·Psychiatry Research. Neuroimaging·Yağmur KırZeynel Baran