A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions.
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 reac...
| Published in: | Psychopharmacology Vol. 238; no. 3; pp. 615 - 638 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Journal Article |
| Published: |
Springer Nature
Mar2021
|
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=149026281&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 149026281 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Mar2021 vid: 238 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 149026281 148006494 10.1007/s00213-020-05746-y 149026281 ppf: 615 ppct: 23 formats: fmt: @attributes: type: P tig: atl: A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions. aug: au: Tan, Madeleine S. A. Honarparvar, Faraz Falconer, James R. Parekh, Harendra S. Pandey, Preeti Siskind, Dan J. affil: School of Pharmacy, The University of Queensland, 20 Cornwall St, 4102, Woolloongabba, QLD, Australia sug: ab: 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. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|