The off-label use of drugs in children and adolescents is widespread. In Germany, the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants (OADs) is not licensed for the treatment of depressive disorders in children and adolescents except for fluoxetine, which was approved in 2006. Against this background, antidepressant drug (ATD) use with a particular focus on off-label prescribing was characterised in a retrospective cohort study including cross-sectional analyses based on claims data of 2,599,685 patients up to 17 years of age. Prevalence of ATD use was 1.84 (95 % CI 1.78–1.90) per 1,000 children in 2004, 1.57 (95 % CI 1.52–1.62) in 2005 and 1.66 (95 % CI 1.61–1.72) in 2006. More than half of all children treated with ATDs (51.29 %) received only one single prescription of an ATD during the study period. Of all prescribed ATDs, 11,172 (42.09 %) were tricyclic antidepressants 9,179 (34.58 %) were SSRIs, 4,371 (16.47 %) were St John’s wort preparations and 1,821 (6.86 %) were OADs. Around half of all children and adolescents who were treated with ATDs were diagnosed with depressive disorders (56.30 %). Overall, 13,035 (49.11 %) of all ATDs were prescribed off-label. Off-label use by age (40.18 %) was found to be more common than off-label use by indication (16.63 %) with 7.70 % of off-label use occurring in both categories. Specialist treatment by hospital-based physicians increased the risk (odds ratio: 2.26, 95 % CI 2.05–2.48) of receiving an off-label prescription compared to treatment by general practitioners. In summary, off-label use of ATDs in children and adolescents was substantial in Germany.