World Journal of Pediatrics

, Volume 15, Issue 1, pp 92–99 | Cite as

Pediatric off-label use of psychotropic drugs approved for adult use in Japan in the light of approval information regarding pediatric patients in the United States: a study of a pharmacy prescription database

  • Nanae Tanemura
  • Maika Asawa
  • Mayuko Kuroda
  • Tsuyoshi Sasaki
  • Yoshiaki Iwane
  • Hisashi UrushiharaEmail author
Original Article



Off-label use of psychotropic prescriptions for pediatric patients has been increasing in Japan. This study sought to clarify pediatric patients’ off-label use of psychotropics approved only for adults in Japan.


This retrospective study on psychotropic utilization employed a pharmaceutical health insurance claims database supplied by a pharmacy for the fiscal year 2016. Seven psychotropic drugs were examined. For each drug, we calculated the proportion of patients aged < 16 years or who were under the approved age limit set in the United States out of all patients. The maximum daily dose of each drug within the study period was plotted by age.


Data of 45,715 patients (female: 26,799, male: 18,916) with 331,920 prescriptions were examined in this study. For each drug, the proportion of pediatric patients aged < 16 years ranged from 0.15 to 1.1%, while the proportion of those under the approved age limit in the United States ranged from 0 to 0.27%. Olanzapine had the highest reported proportion. No drugs other than olanzapine were taken under the approved age limit in the United States.


We identified the pediatric off-label use of psychotropics that were limited to adult use in Japan. The results indicated the possibility of referring to international guidelines or evidence in clinical practice, but these factors do not discount the existing problems with off-label use. More clinical trials within the pediatric population in Japan are needed to address the issue of off-label use and obtain useful and reliable information in the package inserts for rational use in future pediatric patients.


Japan Off-label use Pediatric Prescription Psychotropic drug 



We would like to thank Editage ( for English language editing.

Author contributions

All authors contributed to the design and implementation of this research, the analysis of the results, and writing of the manuscript. All authors approved the final version of the manuscript to be published.



Compliance with ethical standards

Ethical approval

The study protocol was approved by the Keio University Faculty of Pharmacy Ethics Committee for research involving humans (No. 170707-1).

Conflict of interest

TS has received speakers’ honoraria from Daiichi Sankyo, Eli Lilly, Glaxo Smith Kline, Novartis, Janssen, Otsuka, Shionogi, Shire, Taisho and Tanabe Mitsubishi, and he has also received research support from Novartis, Otsuka, Shionogi and Taisho (from April 2014 to April 2018). YI is an employee of KRAFT Inc. HU is a consultant of Eisai Co., Ltd. No financial or non-financial benefits have been or will be received by NT, MA and KM from any party related directly or indirectly to the subject of this article.

Supplementary material

12519_2018_213_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 17 kb)


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Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2018

Authors and Affiliations

  1. 1.Division of Drug Development and Regulatory Science, Faculty of PharmacyKeio UniversityTokyoJapan
  2. 2.Department of Child PsychiatryChiba University HospitalChibaJapan
  3. 3.KRAFT Inc.TokyoJapan

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