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Weight and body mass index increase in children and adolescents exposed to antipsychotic drugs in non-interventional settings: a meta-analysis and meta-regression

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Abstract

Antipsychotics increase weight, BMI and waist size, particularly in pediatric patients. Switching antipsychotics is common practice, thus defining the risk for each antipsychotic in real-life settings can be important for clinical guidance. We conducted a meta-analysis on antipsychotic-related changes in body measures in pediatric observational studies. Of 934 publications found on PubMed, we analyzed 38, including nine treatment arms: no treatment, mixed antipsychotic treatment, first-generation antipsychotics, aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone. Changes in weight, BMI, BMI-Z and waist size were meta-analyzed according to the duration of clinical observations: 6, 12, > 12 months. Meta-regressions probed influencing factors. Weight in Kg was increased at 6, 12, > 12 months by olanzapine [+ 10.91, + 10.7, data not available (n/a)], mixed antipsychotic treatment (n/a, + 9.42, + 12.59), quetiapine (+ 5.84, n/a, n/a) and risperidone (+ 4.47, + 6.01, + 9.51) and without treatment (n/a, + 2.3, n/a). BMI was increased at 6, 12, > 12 months by olanzapine (+ 3.47, + 3.42, n/a), clozapine (n/a, + 3, n/a) mixed antipsychotic treatment (+ 3.37, + 2.95, + 3.32), risperidone (+ 2, + 2.13, + 2.16), quetiapine (+ 1.5, + 1.82, n/a), aripiprazole (n/a, + 1.7, + 2.1) and without treatment (n/a, + 0.75, n/a). BMI-Z was increased at 6, 12, > 12 months by olanzapine (+ 0.94, + 0.98, + 0.89), clozapine (n/a, + 0.8, n/a), risperidone (+ 0.62, + 0.61, + 0.48), quetiapine (+ 0.57, + 0.54, n/a), mixed antipsychotic treatment (+ 0.51, + 0.94, + 0.44), without treatment (n/a, + 0.37, n/a) and aripiprazole (no gain, + 0.31, n/a). Waist size in cm was increased at 6, 12 months by risperidone (+ 8.8, + 11.5), mixed antipsychotics treatment (+ 9.1, + 10.2) and quetiapine (+ 6.9, + 9.1). Overall, olanzapine and clozapine displayed maximum risk, followed by risperidone, quetiapine and aripiprazole (more risky at longer terms); ziprasidone was associated with no gains. No time-based trends emerged, suggesting a drug-specific risk magnitude. Meta-regressions evidenced variable roles for persistence in therapy and follow-up length, increased risk for drug-naïve patients, and a ceiling effect determined by higher baseline BMI/BMI-Z values.

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Funding

This work was supported by the Regional Center of Pharmacovigilance of Lombardy (to EC), the Italian Medicines Agency, Agenzia Italiana del Farmaco (AIFA, to EC) and by the Italian Ministry of Health (Ricerca Corrente 2019–2020, to MP and MN; and Progetto Finalizzata RF-2016-02363761 to EC and AC) which are gratefully acknowledged. The funding public institutions had no role in any part of the work.

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Authors and Affiliations

  1. Scientific Institute IRCCS E. Medea, 23892, Bosisio Parini, LC, Italy

    Marco Pozzi & Maria Nobile

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

    Roberta Ida Ferrentino, Pietro Formisano, Carmela Bravaccio & Simone Pisano

  3. Department of Child and Adolescent Psychiatry and Psychotherapy, Bolzano, Italy

    Giulia Scrinzi

  4. Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Cristina Scavone & Annalisa Capuano

  5. Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, Fatebenefratelli-Sacco Hospital, “Luigi Sacco” University Hospital, Università Di Milano, Via GB Grassi 74, 20157, Milan, Italy

    Sonia Radice, Emilio Clementi & Carla Carnovale

  6. Department of Neuroscience, AORN Santobono-Pausilipon, Naples, Italy

    Simone Pisano

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  1. Marco Pozzi
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  2. Roberta Ida Ferrentino
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  8. Pietro Formisano
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Correspondence to Carla Carnovale.

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Pozzi, M., Ferrentino, R.I., Scrinzi, G. et al. Weight and body mass index increase in children and adolescents exposed to antipsychotic drugs in non-interventional settings: a meta-analysis and meta-regression. Eur Child Adolesc Psychiatry 31, 21–37 (2022). https://doi.org/10.1007/s00787-020-01582-9

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