gms | German Medical Science

Background: Off-label use of drugs in children and adolescents, at variance from the approved use by the regulatory authorities, is widespread due to the lack of clinical trials in children and adolescents. In paediatric wards, off-label use is common, but also in general practice a considerable number of drugs is prescribed off-label. Central nervous system drugs, including antipsychotics (APs) and antidepressants (ATDs), have been intensively prescribed off-label. With this background, AP and ATDuse with a particular focus on off-label prescribing was investigatedon a population level in children and adolescents in Germany.

Materials and Methods: Source of data for this study was the German Pharmacoepidemiological Research Database (GePaRD), which consists of data from four German statutory health insurance providers (SHIs) and includes data of about 17 million insurants throughout Germany. The study population consists of all children and adolescents with data in GePaRD aged 17 years and below in 2004-2011.For incidence and prevalence calculations and for the determination of off-label use, different sub-populations wereconsidered separately.A prescription was classified as off-label if it was either off-label by age, off-label by indication or off-label by contraindication. For the determination of potential off-label use, a reference database was created containing the licensed age, the approved indications and contraindications of every AP and ATD.

Results: The study population for the prevalence study comprised 2,020,316 children in 2004 and 2,159,774 children in 2011.

One-year incidence of AP use increased from 13.7 (95% CI: 13.2-14.3) per 10,000 years in 2005 to 16.8 (95% CI: 15.9-17.8) per 10,000 years in 2011. Prescribing prevalence of APs ranged between 2.4 (95% CI: 2.4-2.4) per 1,000 children in 2004 and 3.5 (95% CI: 3.5-3.6) per 1,000 children in 2011. Throughout the study period, use of conventional APs decreased, while use of atypical APs, mainly risperidone use, increased.Around half of all children and adolescents treated with APs were diagnosed with psychiatric disorders(47.0%). Further common diagnoses were hyperkinetic disorders (46.8%), developmental disorders (38.6%) and restlessness and agitation (21.8%).Off-label use by indication (62.1%) was found to be more common than off-label use by age (12.2%) and off-label use by contraindication (1.4%).

One-year incidence of ATD use increased from 13.3 (95% CI: 12.8-13.9) per 10,000 years in 2005 to 19.1 (95% CI: 18.1-20.2) per 10,000 years in 2011. Prescribing prevalence of ATDs ranged between 2.0 (95% CI: 2.0-2.0) per 1,000 children in 2004 and 2.6 (95% CI: 2.5-2.6) per 1,000 children in 2011. Nearly half of all children and adolescents diagnosed with depressive disorders (44.5%) received only a single prescription of an ATD.Throughout the study period, use of TCAs declined, while use of SSRIs, mainly fluoxetine use, increased. Off-label use by age (29.7%) was more common than off-label use by indication (22.4%) or by contraindication (4.0%).In 2009, nearly half (41.9%) of all children and adolescents treated with ATDs were diagnosed with depressive disorders. Further common diagnoses were psychological disorders(32.9%) and headaches and migraines (25.2%).

Conclusion: APs and ATDs were used for a wide variety of conditions in children and adolescents and off-label use was substantial.However, off-label use by contraindication, which might be most likely associated with safety concerns, was low.The rather short treatment duration with frequently only single prescriptions of ATDs in children diagnosed with depression is of interest and needs to be further explored.