A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions

被引:39
作者
Tan, Madeleine S. A. [1 ]
Honarparvar, Faraz [2 ]
Falconer, James R. [1 ]
Parekh, Harendra S. [1 ]
Pandey, Preeti [1 ]
Siskind, Dan J. [2 ,3 ,4 ]
机构
[1] Univ Queensland, Sch Pharm, 20 Cornwall St, Woolloongabba, Qld 4102, Australia
[2] Univ Queensland, Sch Clin Med, 20 Weightman St, Herston, Qld 4006, Australia
[3] Woolloongabba Community Hlth Ctr, Metro South Addict & Mental Hlth Serv, Mental Hlth, Level 2,228 Logan Rd, Woolloongabba, Qld 4102, Australia
[4] Princess Alexandra Hosp, 199 Ipswich Rd, Woolloongabba, Qld 4102, Australia
关键词
Clozapine; Peripheral adverse drug reaction; Serum level; Schizophrenia; HEART-RATE-VARIABILITY; PLASMA CLOZAPINE; N-DESMETHYLCLOZAPINE; WEIGHT-GAIN; GASTROINTESTINAL HYPOMOTILITY; ATYPICAL ANTIPSYCHOTICS; INDUCED AGRANULOCYTOSIS; ADJUNCTIVE FLUVOXAMINE; SCHIZOPHRENIC-PATIENTS; METABOLITES;
D O I
10.1007/s00213-020-05746-y
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rationale Clozapine is the most effective antipsychotic for treatment-refractory schizophrenia for reducing positive psychotic symptoms. It is associated with a reduction in hospitalisation and overall mortality. In spite of this, clozapine remains underutilised due to its complex adverse drug reaction (ADR) profile. Objective This systematic review aims to investigate the association of clozapine and norclozapine serum levels, and peripheral ADRs. Methods Studies were searched from four electronic databases (PubMed, EMBASE, PsycINFO and CINAHL) from inception to 12 June 2020. Studies were included if they had adult patients, provided data on steady-state trough clozapine or norclozapine levels and reported on clozapine-associated ADRs. Pregnant women, case reports and series were excluded. Results A statistically significant correlation was found for clozapine serum levels and triglycerides (n = 70; r = 0.303, 95% CI 0.0119-0.546, p = 0.042), heart rate (n = 137; r = 0.269, 95% CI 0.0918-0.486, p = 0.035), and overall combined ADRs (n = 160; r = 0.264, 95% CI 0.110-0.405, p = 0.001), but not for absolute neutrophil count (n = 223; r = - 0.164, 95% CI - 0.529-0.253, p = 0.444) or total white cell count (n = 18; r = 0.0176, 95% CI - 0.203-0.237, p = 0.878). Interestingly, norclozapine serum levels were found to be statistically correlated to triglycerides (n = 120; r = 0.211, 95% CI 0.0305-0.378, p = 0.022), total cholesterol (n = 120; r = 0.272, 95% CI 0.0948-0.432, p = 0.003) and weight gain (n = 118; r = 0.208, 95% CI 0.0261-0.377, p = 0.025). Conclusions Heart rate, triglycerides and combined ADRs are significantly correlated with clozapine levels, and triglycerides, total cholesterol and weight gain with norclozapine levels. Future prospective, randomised controlled studies are needed to identify the cause-effect relationship between clozapine levels and peripheral ADRs.
引用
收藏
页码:615 / 637
页数:23
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