(239) Off-label use of antidepressants among pediatric patients in China

Background: Off-label use of antidepressant in children is common worldwide, despite that it may expose pediatric patients to unknown risks of adverse drug reactions and unsuccessful treatment.

Objectives: This study aimed to investigate the off-label use of antidepressants that are approved by the FDA and recommended by Micromedex database for use in both adult and pediatric populations but are only permitted for use in adults in China.

Methods: This retrospective study extracted electronic health records (EHR) of seven major mental health institutions in China from the China’s Psychiatric-Specialized Medical Center database in 2019.Antidepressants were identified from the National Drug Code and the Drugs@FDA databases via the official website of China's National Medical Products Administration (NMPA) and the US Food and Drug Administration.In addition,the evidence from the IBM Micromedex -Thomson grading system of effectiveness level IIa,recommendation level at IIb, and evidence level B and above was also used as the basis for off-label use.We analyzed the proportion of pediatric patients (age 0-18 years) and of patients who were outside the age limit approved by the FDA and recommended by Micromedex database among all identified users of the sampled antidepressants.The maximum daily dose of each drug within the study period was plotted by age.

Results: As of January 2019, five antidepressants that were approved only for adult use in China but were approved by FDA for pediatric patients and recommended by Micromedex database were identified and included in this study. A total of 76,120 patients (55,617 females and 20,503 males) with 303,252 prescriptions were included. For each included antidepressant, the proportion of pediatric patients among all its users ranged from 1.09 to 6.85% while the proportion of patients whose age was outside of the age range approved by the FDA and recommended by the Micromedex database ranged from 0.02 to 0.08%. Citalopram and venlafaxine were the antidepressant reporting the highest proportion of pediatric users. Furthermore, almost all pediatric patients who were prescribed the studied off-label antidepressants were within the age range approved by the FDA and recommended by the Micromedex database but were prescribed at a lower dose than the dose range approved by the FDA and recommended by the Micromedex database.

Conclusions: The off-label use of antidepressants was more prevalent among Chinese pediatric patients than among those residing in European and American countries and regions.Our findings highlight an urgent need to generate evidence by conducting clinical trials involving pediatric patients and through long-term pharmacovigilance as well as to better assess the benefit/risk ratio of drugs used off-label and promote the rational prescribing of antidepressants for Chinese pediatric patients.