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Introduction: There has been an increase in the prescription of antidepressants (AD) in primary care (PC). However, it is unclear whether this was explained by a rise in diagnoses with an indication for AD. We investigated the changes in frequency and the variables associated with AD prescription in Catalonia, Spain., Methods: We retrieved AD prescription, sociodemographic, and health-related data using individual electronic health records from a population-representative sample (N=947.698) attending PC between 2010 and 2019. Prescription of AD was calculated using DHD (Defined Daily Doses per 1000 inhabitants/day). We compared cumulative changes in DHD with cumulative changes in diagnoses with an indication for AD during the study period. We used Poisson regression to examine sociodemographic and health-related variables associated with AD prescription., Results: Both AD prescription and mental health diagnoses with an indication for AD gradually increased. At the end of the study period, DHD of AD prescriptions and mental health diagnoses with an indication for AD reached cumulative increases of 404% and 49% respectively. Female sex (incidence rate ratio (IRR)=2.83), older age (IRR=25.43), and lower socio-economic status (IRR=1.35) were significantly associated with increased risk of being prescribed an AD., Conclusions: Our results from a large and representative cohort of patients confirm a steady increase of AD prescriptions that is not explained by a parallel increase in mental health diagnoses with an indication for AD. A trend on AD off-label and over-prescriptions in the PC system in Catalonia can be inferred from this dissociation., (Copyright © 2022 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Publicado por Elsevier España, S.L.U. All rights reserved.)