Journal ArticleDOI
Clozapine serum levels and side effects during steady state treatment of schizophrenic patients: a cross-sectional study.
O V Olesen,Klaus Thomsen,P N Jensen,C H Wulff,N A Rasmussen,C Refshammer,Jette Led Sørensen,M Bysted,J Christensen,Raben Rosenberg +9 more
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TLDR
It is concluded that clozapine fulfils the criteria for therapeutic drug monitoring and TDM may contribute to finding the lowest effective dose with the fewest possible side effects.Abstract:
Serum clozapine (S-Cloza) and serum desmethyl-clozapine concentrations (S-Descloza) were measured in 30 chronic schizophrenic in- and outpatients on a variable dose regimen. All patients were in steady state with respect to clozapine therapy and in a stable condition with respect to psychotic illness. The 24-h clozapine dose (median with interquartile range in parenthesis) was 350 (228–425) mg/24 h (range 100–700). There was a weak positive correlation between doses and the BPRS total score (r=0.44,P<0.05). The median S-Cloza was 1076 (706–1882) nmol/l (range 196–5581 corresponding to 64–1824 ng/ml). The S-Cloza was linearly correlated to dose but with a high interindividual variation at equal doses, e.g. a factor of 8 at 400 mg/24 h, but a low intraindividual variability of 20%. The S-Descloza averaged 77% of the S-Cloza and was highly correlated to S-Cloza (r=0.90;P<0.001). The S-Descloza/dose ratio increased with age and duration of treatment. The side effects registered were EEG abnormalities (83%), tachycardia (23%), increased liver enzyme activity (60%), orthostatic hypotension (17%), and moderate leucocytosis (17%). Only EEG changes were correlated to S-Cloza (r=0.43;P<0.05). The score values of the UKU Side Effect Scale were weakly (r=0.36) correlated to S-Cloza. No side effects were correlated to S-Descloza, doses, or treatment duration. The frequency of side effects was higher than in studies using lower mean doses indicating a correlation between doses or S-Cloza and the frequency of side effects. It is concluded that clozapine fulfils the criteria for therapeutic drug monitoring. TDM may contribute to finding the lowest effective dose with the fewest possible side effects.read more
Citations
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The atypical antipsychotics clozapine and olanzapine promote down-regulation and display functional selectivity at human 5-HT7 receptors.
Kjetil Wessel Andressen,Kjetil Wessel Andressen,Ornella Manfra,Ornella Manfra,C H Brevik,Andrea Hembre Ulsund,Andrea Hembre Ulsund,Peter Vanhoenacker,Finn Olav Levy,Finn Olav Levy,Kurt A. Krobert,Kurt A. Krobert +11 more
TL;DR: This study found that inverse agonists induce both homo‐ and heterologous desensitization, similar to agonist stimulation, at the Gs‐coupled 5‐HT7 receptor.
Journal ArticleDOI
A review of the clinical utility of serum clozapine and norclozapine levels
TL;DR: Treatment refractory schizophrenia is a serious issue affecting at least 30% of all patients with schizophrenia despite the continued emergence of new agents aimed at treating this disease.
Journal ArticleDOI
A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions
Madeleine S. A. Tan,Faraz Honarparvar,James R. Falconer,Harendra S. Parekh,Preeti Pandey,Dan Siskind,Dan Siskind +6 more
TL;DR: In this article, the authors investigated the association of clozapine and norclozaphine serum levels, and peripheral ADRs, and found a statistically significant correlation was found for the clozabine levels and triglycerides, heart rate, triglycerides and combined ADRs.
Journal ArticleDOI
Effects of the antipsychotics haloperidol, clozapine, and aripiprazole on the dendritic spine.
Manabu Takaki,Masafumi Kodama,Yutaka Mizuki,Hiroki Kawai,Bunta Yoshimura,Makiko Kishimoto,Shinji Sakamoto,Yuko Okahisa,Norihito Yamada +8 more
TL;DR: Aripiprazole, clozapine, and haloperidol differentially regulate the dendritic spine, and this effect may occur through the AKT-GSK-3 beta cascade.
Journal ArticleDOI
Development and validation of an HPLC method for the simultaneous determination of clozapine and desmethylclozapine in plasma of schizophrenic patients
TL;DR: In this article, a high-performance liquid chromatographic method with amperometric detection has been developed for the determination of levels of clozapine (CLZ) and its active metabolite N-desmethylclozapines (DMC) in human plasma.
References
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Journal ArticleDOI
The Brief Psychiatric Rating Scale
John E. Overall,Donald R. Gorham +1 more
TL;DR: The Brief Psychiatric Rating Scale (BRS) as mentioned in this paper was developed to provide a rapid assessment technique particularly suited to the evaluation of patient change, and it is recommended for use where efficiency, speed, and economy are important considerations.
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Verapamil: A Review of its Pharmacological Properties and Therapeutic Use
TL;DR: Experimental and clinical data suggest that verapamil will become an important and safe addition to existing drug regimens, especially as an agent of choice for the short-term treatment of most cases of paroxysmal supraventricular tachycardias and in the maintenance of sinus rhythm following cardioversion of atrial fibrillation.
Journal ArticleDOI
Clozapine. A novel antipsychotic agent.
TL;DR: This review considers the discovery of clozapine; its chemistry, pharmacologic activities, metabolism, and pharmacokinetics; evidence of its efficacy; and its side effects and appropriate clinical use.