Utilisation of drugs for the treatment of psychiatric diseases in the pediatric population: focus on off-label use

Abstract

Psychotropics are increasingly used in pediatrics, often as off-label medicines. The guarantees of safety and efficacy are not always granted in clinical practice compared to adult authorised indications. A retrospective observational study was done to estimate the prevalence of psychotropic use in pediatric subjects of Catalonia (Spain). Anonymised data on dispensation of psychotropics to pediatric patients, demography and other related data were obtained by the local healthcare management for the period 2008–2017. Estimation of off-label use was done through description of drug dispensations with no authorised use related to age range. The prevalence of psychotropics was 40.8–64.2 per 1,000 pediatric inhabitants. Hydroxyzine-only represented two-thirds of dispensations, and when removed, the prevalence dropped to 26.4–32.2 per 1,000 pediatric inhabitants. Adolescents and boys were more likely to receive a psychotropic. Psychostimulants had the highest exposure rate, mainly due to methylphenidate. Off-label use was observed in 12% of subjects, corresponding to 4.6% of all dispensed psychotropics with boys being more exposed. The proportion of off-label use vs. labelled use was higher in younger populations. Aripiprazole had the highest off-label frequency. Our data support the frequent reality of off-label use in pediatrics, despite the potential underestimation related to the selected off-label definition. There is an urgent need to systematically ascertain effectiveness and any potential adverse events in the off-label pediatric setting, and to generate valuable information for risk-benefit assessment in these populations where extrapolation from adults is not reliable.

Prevalence of use of on-label and off-label psychotropics in the Greek pediatric population

“…In this way, dispensed antiepileptics have less risk to remain underestimated. Compared to previously reported rates of antiepileptics’ prevalence, Greece had similar ones to those reported in the Netherlands (3.7-4 per 1,000) ( van de Vrie-Hoekstra et al, 2008 ; Zito et al, 2008 ) and Germany (3.8 per 1,000) ( Zito et al, 2008 ), while in Spain (4.97 per 1,000) ( Pesiou et al, 2023 ) and the United Kingdom (7.3–8.69 per 1,000) the reported rates were higher. ( Ackers et al, 2007 ).…”

“…The percentage of the overall off-label dispensations based on lack of pediatric recommendation in the SmPC was 5.5% in Greece; if the range of the recommended age was taken into consideration, then the percentage increased into 7.5%, with the younger populations mostly exposed to off-label dispensations as well as girls. Comparing with rates from other regions, Greece has similar rates with those observed in Spain (Pesiou et al, 2023), but much less exposure to off-label psychotropics than the one reported in Iceland (Zoëga et al, 2009).…”

“…The psychotropic exposure rates we describe in the Greek pediatric population are amongst the lowest estimates considering other regions both in and outside Europe (Zito et al, 2003;Safer et al, 2004;Zito et al, 2008;Zoëga et al, 2009;Kovess Masfety et al, 2015;Pesiou et al, 2023); no previous Greek data were identified in the literature to check for consistency or to compare any change in the trends. In particular, psychostimulants use was the lowest among other regions (Schirm et al, 2001;Faber et al, 2005;Vinker et al, 2006;Zito et al, 2008;Pottegård et al, 2012;Bachmann et al, 2017;Pesiou et al, 2023), approaching the rates reported in Italy (0.1-1.9 per 1,000) (Piovani et al, 2016). It is possible that our data source underestimated exposure bias, but the database collects information from a model for reimbursement that is almost universal, with coverage over 97.3% of the Greek population (ΗΔΙΚΛ, 2012;Yfantopoulos and Chantzaras, 2018;Bakirtzis et al, 2020).…”

Trends in antipsychotic use among children and adolescents in Germany: a study using 2011–2020 nationwide outpatient claims data

“…Antipsychotics (APs) were originally developed for the treatment of severe psychiatric disorders like schizophrenia and bipolar disorder but are now increasingly used for the treatment of restlessness, agitation, anxiety, sleep disorders, and other off-label indications (6). Particularly in children and adolescents, the off-label use of APs is common (7,8). Even though an off-label use is often unavoidable in pediatric care, it potentially increases the risk of adverse events (9)(10)(11).…”