PURPOSE: To study the use of antidepressants in children and adolescents in Dutch general practice in 2001 and 2005 and to determine off-label prescribing. METHODS: Data were obtained from the Netherlands Information Network of General Practice (LINH) that comprised 97 practices in 2001 and 73 practices in 2005. General practitioners (GPs) recorded prescriptions with their indication in the medical records of the patients during one calendar year. We selected boys and girls aged 0-17 years (n = 83 442 in 2001; n = 62 969 in 2005) and identified those who got prescribed antidepressants (N06A). Prevalence of use, indications and percentage of off-label prescriptions were compared between 2001 and 2005. RESULTS: The prevalence of selective serotonin reuptake inhibitor (SSRI) use decreased from 1.2 to 1.1 per 1000 children and adolescents between 2001 and 2005. The use of tricyclic antidepressants (TCAs) and other antidepressants also decreased (0.8 to 0.7 and 0.3 to 0.2, respectively). TCAs were often prescribed for nocturnal enuresis, but in patients aged 12-17 years hyperactivity was the leading indication in both years. GPs continued to prescribe SSRIs for depression (about half of the prescriptions) after the safety warnings, while venlafaxine prescribed for depression decreased in favour of anxiety. Off-label prescribing of SSRIs increased from 16.7% to 34.4% and that of venlafaxine from 22.2% to 58.3%. All SSRI and venlafaxine prescriptions were unlicensed for age. CONCLUSIONS: The decreased use of SSRIs and venlafaxine suggests an impact of the safety warnings. A point of concern is the enlarged off-label prescribing and insight in the underlying reasons and its appropriateness is needed. (aut. ref.