Therapeutic drug monitoring of second-generation antipsychotics in pediatric patients: an observational study in real-life settings

Pozzi, Marco; Cattaneo, Dario; Baldelli, Sara; Fucile, Serena; Capuano, Annalisa; Bravaccio, Carmela; Sportiello, Liberata; Bertella, Silvana; Auricchio, Fabiana; Bernardini, Renato; Ferrajolo, Carmen; Guastella, Giuseppe; Mani, Elisa; Carnovale, Carla; Pisano, Simone; Rafaniello, Concetta; Riccio, Maria Pia; Rizzo, Renata; Scuderi, Maria Grazia; Sperandeo, Serena; Villa, Laura; Pascotto, Antonio; Molteni, Massimo; Rossi, Francesco; Radice, Sonia; Clementi, Emilio

doi:10.1007/s00228-015-1982-0

Cited by 23 publications

(19 citation statements)

References 34 publications

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“…The extrapolation of therapeutic reference ranges -which have been established in adult patients -to paediatric patients, especially to young children, has to be investigated for every single substance, as preliminary TDM studies in paediatric neuropsychiatry provided divergent results. Fortunately, however, several studies have demonstrated similar therapeutic reference ranges for children/adolescents and adults (e. g., sertraline [1177], aripiprazole [949,1311], fluvoxamine [677]). For most substances, a high interindividual variability in drug concentrations after administration of the same dose was shown in children and adolescents.…”

Section: Recommendationmentioning

confidence: 99%

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

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Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

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Section: Recommendationmentioning

confidence: 99%

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

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“…Its half‐life of up to 37 hr means that steady state and sustained efficacy for CINV may take a few days to achieve. Studies suggest no appreciable difference in olanzapine pharmacokinetics between children and adults …”

Section: Clinicial Considerationsmentioning

confidence: 99%

“…Concomitant usage of metoclopramide and olanzapine is contraindicated due to additive risk for EPS. Long‐term risk is unclear given relatively recent availability of olanzapine and ongoing research and phase 4 long‐term surveillance safety trials …”

Section: Cautionsmentioning

confidence: 99%

“…Although some guidelines recommend starting doses of 5 or 10 mg, these doses may be excessive and sedating for children and adolescents. 3,[5][6][7] Dosing is an individualized process, as milligram per kilogram dosing is not data driven. Starting low and titrating slow at 1.25 or 2.5 mg BID minimizes side effects.…”

Section: Dosingmentioning

confidence: 99%

“…With a time to peak serum concentration of 1-3 hr orally and 15-45 min intramuscularly (IM), dosing q4 hr orally is possible, although 2-3 times a day is more typical. 5,7 Using it regularly dosed and/or as PRN breakthrough medication can simplify the medication regime, minimizing potential adverse effects.Its half-life of up to 37 hr means that steady state and sustained efficacy for CINV may take a few days to achieve. Studies suggest no…”

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confidence: 99%

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Olanzapine for chemotherapy‐induced nausea: Lessons learned from child and adolescent psychiatry

Samsel

Kearney

Meadows

et al. 2018

Pediatric Blood & Cancer

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

et al. 2022

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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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Therapeutic drug monitoring of second-generation antipsychotics in pediatric patients: an observational study in real-life settings

Cited by 23 publications

References 34 publications

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Olanzapine for chemotherapy‐induced nausea: Lessons learned from child and adolescent psychiatry

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

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