Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis

阿立哌唑 精神分裂症(面向对象编程) 人口 治疗药物监测 神经影像学 心理学 医学 治疗指标 药理学 精神科 药品 内科学 肿瘤科 临床心理学 环境卫生
作者
X.M. Hart,Christoph Hiemke,Luzie Eichentopf,Xenija Lense,Hans Willi Clement,Andreas Conca,Frank Faltraco,Vincenzo De Florio,Jessica Grüner,Ursula Havemann‐Reinecke,Espen Molden,Michael Paulzen,Georgios Schoretsanitis,Thomas Riemer,Gerhard Gründer
出处
期刊:Psychopharmacology [Springer Science+Business Media]
卷期号:239 (11): 3377-3391 被引量:22
标识
DOI:10.1007/s00213-022-06233-2
摘要

Abstract Rationale While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges. Objectives Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders. Methods The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed ( N = 3,373) and pharmacokinetic influences investigated. Results Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120–270 ng/ml and 180–380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders. Conclusions High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers.
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