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Metabolic events associated with the use of antipsychotics in children, adolescents and young adults: a multinational sequence symmetry study

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Abstract

It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6–30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00–1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88–1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04–1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85–1.12) and 1.24 (95% CI 0.97–1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns.

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Acknowledgements

This study was supported by a grant from the Ministry of Science and Technology of Taiwan (ID: 106-2320-B-006-025-MY2). The funding source had no role in the design, analysis, interpretation, or reporting of results or in the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Research Department of Practice and Policy, UCL School of Pharmacy, London, UK

    Kenneth K. C. Man & Ian C. K. Wong

  2. Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China

    Kenneth K. C. Man & Ian C. K. Wong

  3. School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 701, Taiwan

    Shih-Chieh Shao, Chien-Chou Su, Yea-Huei Kao Yang & Edward Chia-Cheng Lai

  4. Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

    Shih-Chieh Shao

  5. Department of Pharmacotherapy, College of Pharmacy, University of Utah, 30 2000 E, Salt Lake City, UT, 84112, USA

    Nathorn Chaiyakunapruk

  6. School of Pharmacy, Monash University Malaysia, Selangor, Malaysia

    Nathorn Chaiyakunapruk

  7. Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand

    Piyameth Dilokthornsakul

  8. NPO Drug Safety Research Unit Japan, Tokyo, Japan

    Kiyoshi Kubota

  9. School of Pharmacy, Sungkyunkwan University, Seoul, South Korea

    Junqing Li & Ju-Young Shin

  10. Department of Clinical Pharmacy, Nihon University School of Pharmacy, Chiba, Japan

    Nobuhiro Ooba

  11. Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, Australia

    Nicole Pratt & Elizabeth E. Roughead

  12. Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark

    Anton Pottegård

  13. Department of Pharmacy, National Cheng Kung University Hospital, Tainan, Taiwan

    Lotte Rasmussen, Chien-Chou Su & Edward Chia-Cheng Lai

Authors
  1. Kenneth K. C. Man
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  2. Shih-Chieh Shao
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  8. Nicole Pratt
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  11. Elizabeth E. Roughead
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  12. Ju-Young Shin
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  15. Yea-Huei Kao Yang
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  16. Edward Chia-Cheng Lai
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Corresponding author

Correspondence to Edward Chia-Cheng Lai.

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Appendix

Appendix

See Figs. 5, 6, 7, 8 and Tables 1, 2, 3, 4.

Fig. 5
figure 5

Age and sex distribution of the patients receiving antipsychotics among countries

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Fig. 6
figure 6

Distribution of antipsychotics use by years and countries

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Fig. 7
figure 7

Sensitivity analysis: associations between antipsychotics and composite metabolic events (excluding Thailand and Japan)

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Fig. 8
figure 8

Sensitivity analysis: associations between antipsychotics and individual outcomes (excluding Thailand and Japan). a Hypertension, b Hyperglycemia, or c Dyslipidemia

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Table 1 Summary of participating databases
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Table 2 Codes for antipsychotics
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Table 3 Subgroup analysis: associations for specific outcomes by typical and atypical antipsychotics
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Table 4 The number of patients of each country used for sequence symmetry analysis for outcomes
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Man, K.K.C., Shao, SC., Chaiyakunapruk, N. et al. Metabolic events associated with the use of antipsychotics in children, adolescents and young adults: a multinational sequence symmetry study. Eur Child Adolesc Psychiatry 31, 99–120 (2022). https://doi.org/10.1007/s00787-020-01674-6

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  • DOI: https://doi.org/10.1007/s00787-020-01674-6

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