Objective: The purpose of this study was to determine if plasma clozapine levels were associated with treatment response.
Method: To examine this question, neuroleptic nonresponsive patients with schizophrenia or schizoaffective disorder were given clozapine, which was titrated to 500 mg/day by day 14 of treatment, and the dose was held fixed at least through day 21. Subsequently, clozapine doses were adjusted as clinically indicated, up to a maximum of 900 mg/day. Plasma clozapine levels were obtained at weeks 3 and 6, and standard clinical ratings (Brief Psychiatric Rating Scale [BPRS] and Clinical Global Impression) were done at baseline and at weeks 3 and 6.
Results: Data from 45 subjects were analyzed. There were no correlations between plasma clozapine levels and change in BPRS scores at treatment weeks 3 and 6. However, when the subjects were classified as responders or nonresponders, therapeutic response was associated with clozapine blood levels above 350 ng/ml.
Conclusions: This study suggest that clozapine blood levels are correlated with clinical response.
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http://dx.doi.org/10.1176/ajp.152.2.179 | DOI Listing |
J Clin Psychopharmacol
December 2024
Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Purpose/background: Clozapine is the recommended drug for treatment-resistant schizophrenia. Drug response could be affected by numerous factors such as age, sex, body mass index, co-medication, consumption of xanthine-containing beverages, smoking, and genetic variants of the enzymes involved in clozapine metabolism (CYP1A2, CYP3A4, and, to a lesser extent, CYP2C19 and CYP2D6). This study evaluated genetic and nongenetic variables that may affect clozapine plasma concentrations in Uruguayan patients with schizophrenia.
View Article and Find Full Text PDFJ Neuroinflammation
December 2024
Department of Neurosurgery, Stanford University School of Medicine, 1050 Arastradero Road, Building A, Palo Alto, Stanford, CA, 94304, United States of America.
Norepinephrine (NE) modulates cognitive function, arousal, attention, and responses to novelty and stress, and it also regulates neuroinflammation. We previously demonstrated behavioral and immunomodulatory effects of beta-adrenergic pharmacology in mouse models of Alzheimer's disease (AD). The current studies were designed to block noradrenergic signaling in 5XFAD mice through (1) chemogenetic inhibition of the locus coeruleus (LC), (2) pharmacologic blocking of β-adrenergic receptors, and (3) conditional deletion of β1- or β2-adrenergic receptors (adrb1 or adrb2) in microglia.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, Japan.
The involvement of drug-metabolizing enzymes and transporters in plasma clozapine (CLZ) dynamics has not been well examined in Japanese patients with treatment-resistant schizophrenia (TRS). Therefore, this clinical study investigated the relationship between single nucleotide polymorphisms (SNPs) of various pharmacokinetic factors (drug-metabolizing enzymes and transporters) and dynamic changes in CLZ. Additionally, we aimed to determine whether CLZ acts as a substrate for pharmacokinetic factors using in vitro assays and molecular docking calculations.
View Article and Find Full Text PDFTher Adv Psychopharmacol
December 2024
Department of Community Mental Health, Mental Health Service Noord-Holland Noord, Alkmaar, The Netherlands.
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