Clozapine levels as a predictor for therapeutic response: A systematic review and meta-analysis.

Tytuł:: Clozapine levels as a predictor for therapeutic response: A systematic review and meta-analysis.
Autorzy:: Siskind D; Metro South Addiction and Mental Health Service, Brisbane, QLD, Australia.; School of Clinical Medicine, University of Queensland, Brisbane, QLD, Australia.; Physical and Mental Health Stream, Queensland Centre for Mental Health Research, Brisbane, QLD, Australia.
Sharma M; School of Clinical Medicine, University of Queensland, Brisbane, QLD, Australia.; Cairns Base Hospital, Cairns, QLD, Australia.
Pawar M; School of Clinical Medicine, University of Queensland, Brisbane, QLD, Australia.; Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Pearson E; School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia.
Wagner E; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
Warren N; Metro South Addiction and Mental Health Service, Brisbane, QLD, Australia.; School of Clinical Medicine, University of Queensland, Brisbane, QLD, Australia.; Physical and Mental Health Stream, Queensland Centre for Mental Health Research, Brisbane, QLD, Australia.
Kisely S; Metro South Addiction and Mental Health Service, Brisbane, QLD, Australia.; School of Clinical Medicine, University of Queensland, Brisbane, QLD, Australia.; Physical and Mental Health Stream, Queensland Centre for Mental Health Research, Brisbane, QLD, Australia.; Departments of Psychiatry, Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada.
Źródło:: Acta psychiatrica Scandinavica [Acta Psychiatr Scand] 2021 Nov; Vol. 144 (5), pp. 422-432. Date of Electronic Publication: 2021 Aug 25.
Typ publikacji:: Meta-Analysis; Research Support, Non-U.S. Gov't; Systematic Review
Język:: English
Imprint Name(s):: Publication: Malden, MA : Wiley-Blackwell
Original Publication: Copenhagen : Munksgaard International Publishers
MeSH Terms:: Antipsychotic Agents*/therapeutic use
Clozapine*/therapeutic use
Drug-Related Side Effects and Adverse Reactions*
Schizophrenia*/drug therapy
Humans
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Contributed Indexing:: Keywords: clozapine; levels; meta-analysis; relapse; response
Substance Nomenclature:: 0 (Antipsychotic Agents)
J60AR2IKIC (Clozapine)
Entry Date(s):: Date Created: 20210810 Date Completed: 20211108 Latest Revision: 20211108
Update Code:: 20240105
DOI:: 10.1111/acps.13361
PMID:: 34374073
: Raport

Pełny tekst

Objectives: Clozapine levels may be a more useful predictor of therapeutic response than the dose, given the variability in clozapine metabolism between individuals. We therefore systematically reviewed and meta-analysed the impact of clozapine levels on response and/or relapse to provide guidance on optimal clozapine levels.
Methods: We systematically searched PubMed, PsycInfo and Embase for studies exploring clozapine levels and response and/or relapse. Our primary meta-analysis was rates of response above and below clozapine level thresholds of 350 ng/ml and 600 ng/ml. Secondary analyses were undertaken of mean clozapine levels, dose and concentration/dose (C/D) ratio and response and/or relapse. A meta-regression by study duration was conducted.
Results: Twenty studies met inclusion criteria. Clozapine levels above 350 ng/ml were associated with statistically significantly higher rates of response (OR 2.27 95% CI 1.40-3.67, p < 0.001), but not above 600 ng/ml (OR 1.40 95% CI 0.85-2.31, p = 0.19). Higher mean clozapine levels were associated with better rates of response (SMD 0.24, 95% CI 0.00-0.49, p = 0.05), and lower rates of relapse (SMD -0.72, 95% CI -1.26 to -0.19, p = 0.008). By contrast, neither clozapine dose nor C/D ratio was associated with differing rates of response. Similarly, study duration did not affect outcome.
Conclusions: Our findings are in keeping with current guidelines that recommend targeting clozapine levels above 350 ng/ml before augmentation is considered. As some clozapine associated ADRs are dose dependent, levels above 600 ng/ml may have an unfavourable risk-benefit ratio.
(© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Comment in: Acta Psychiatr Scand. 2021 Nov;144(5):419-421. (PMID: 34622947)

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