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

  • Pharmacokinetics and Disposition
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Available guidelines on therapeutic drug monitoring of second-generation antipsychotics were designed for adults; therefore, they cannot be transferred as such in pediatric patients, who may have different drug absorption, distribution, metabolism, and elimination. Moreover, available tools that guide dosing in neuropsychiatric pediatric patients are scant, leading to the possibility of reduced efficacy and/or increased risks of toxicity. Here we describe the results of observational therapeutic drug monitoring conducted in three pediatric neuropsychiatry units across Italy in 2012–2014, with the following aims: (1) to describe the distribution of plasma concentrations of second-generation antipsychotics in our pediatric patients and (2) to identify clinical covariates associated with plasma drug levels.

Methods

Five hundred fifty-six plasma trough concentrations of the second-generation antipsychotics risperidone (plus 9-hydroxy-risperidone), aripiprazole, olanzapine, and quetiapine were measured from 172 pediatric outpatients overall. The distribution of drug concentrations was described and correlated with drug doses and clinical variables.

Results

Risperidone plasma levels were lower than in adults (median 13.6 ng/ml), with a high inter-patient (78.9 %) but lower intra-patient (34.2 %) variability. In multiple regression analyses, risperidone plasma levels depended only on drug dose (p < 0.001). Aripiprazole plasma levels were similar to those described in adults (median 165.8 ng/ml) and were widely distributed, with an inter-patient variability of 81.1 %, while the intra-patient variability was much lower (29.3 %). Multiple regression analyses indicated that aripiprazole plasma levels were influenced by the daily doses (p < 0.001) and by the number of concomitant drugs (p < 0.01).

Conclusion

Our study described the distribution of plasma levels of SGAs in a real-life setting involving pediatric patients, significantly increasing the amount of available data for this fragile population. If confirmed in larger dataset, these data may contribute to the definition of optimal therapeutic window for risperidone and aripiprazole plasma levels in pediatric patients.

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Acknowledgments

We are thankful to Prof. Piergiorgo Duca, M.D. (Medical Statistics and Biometry Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy) for the precious advice on the conception, choice, and conduction of statistical analyses.

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Authors and Affiliations

  1. Scientific Institute IRCCS Eugenio Medea, 23842 Bosisio Parini, Lecco, Italy

    Marco Pozzi, Silvana Bertella, Elisa Mani, Laura Villa, Massimo Molteni & Emilio Clementi

  2. Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, L. Sacco University Hospital, Università di Milano, 20157, Milan, Italy

    Dario Cattaneo, Sara Baldelli, Serena Fucile, Carla Carnovale & Sonia Radice

  3. Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Second University of Naples, 80131, Naples, Italy

    Annalisa Capuano, Liberata Sportiello, Fabiana Auricchio, Carmen Ferrajolo, Concetta Rafaniello & Francesco Rossi

  4. Department of Translational Medical Sciences, University Federico II of Naples, 80131, Naples, Italy

    Carmela Bravaccio

  5. Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, School of Medicine, University of Catania, 95131, Catania, Italy

    Renato Bernardini & Giuseppe Guastella

  6. Department of Mental and Physical Health and Preventive Medicine, Child and Adolescent Psychiatry Division, Second University of Naples, 80131, Naples, Italy

    Simone Pisano, Maria Pia Riccio, Serena Sperandeo & Antonio Pascotto

  7. Child and Adolescent Neuropsychiatry, Department of Medical and Paediatric Sciences, School of Medicine, University of Catania, 95131, Catania, Italy

    Renata Rizzo & Maria Grazia Scuderi

  8. Unit of Clinical Pharmacology, CNR Institute of Neuroscience, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Università di Milano, 20157, Milan, Italy

    Emilio Clementi

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  1. Marco Pozzi
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Corresponding author

Correspondence to Emilio Clementi.

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Funding

This work was supported by Agenzia Italiana del Farmaco (MEAP multiregional project, to EC and FR) and by the Italian Ministry of Health (Ricerca Corrente 2015, to EC and MM). The funding public institutions had no role in any part of the work.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Ethics Committees of all participating structures.

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Pozzi, M., Cattaneo, D., Baldelli, S. et al. Therapeutic drug monitoring of second-generation antipsychotics in pediatric patients: an observational study in real-life settings. Eur J Clin Pharmacol 72, 285–293 (2016). https://doi.org/10.1007/s00228-015-1982-0

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  • DOI: https://doi.org/10.1007/s00228-015-1982-0

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