Over the past decade, increasing off-label use of quetiapine has been reported worldwide from various sources. We wanted to investigate how this is reflected in therapeutic drug monitoring (TDM) data. Requisitions for serum concentration measurements of quetiapine from a TDM service in Central Norway during 2001-2019 were obtained and analysed for age, gender, trends in quetiapine doses, serum concentrations and indicators of diagnoses. There were 19 759 requisitions from 7459 individuals. Daily doses of quetiapine decreased by 24 mg per year (95% CI: -25.61 to -21.48, p < 0.001, N = 4505). A corresponding decrease in quetiapine serum concentrations was not seen. The proportion of requisitions with diagnoses indicating reimbursable use was 13% for the whole study period. Mean daily doses were slightly higher in the reimbursable group, but declined over time in these samples, as well. To our understanding, these results signal a trend towards lower prescribed doses of quetiapine, possibly reflecting drug repurposing and/or off-label use. The discrepancy in the decrease of doses versus serum concentrations may reflect the intake of higher doses than prescribed and/or inappropriate TDM sampling. Our findings show that TDM data have limitations when it comes to making inferences about the use of quetiapine based on serum concentrations and clinical information on the requisitions.