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Background: Depression and anxiety have increased in prevalence since the start of the COVID-19 pandemic., Objective: To evaluate the consumption of antidepressants and anxiolytics from 2012 to 2022 and the pandemic's potential impact in France., Methods: We conducted an interrupted time series analysis of routine drug sales data (Medic'AM) from all French outpatient pharmacies from 2012 to 2022. We investigated trends in defined daily doses of antidepressants and anxiolytics sold per 1000 inhabitants (DDD/TID) and related expenditures before and after pandemic onset and in relation with stringency of pandemic mitigation measures. Analyses were performed descriptively and using segmented linear regression, autoregressive and autoregressive integrated moving average models., Findings: From 2012 to 2019, overall monthly antidepressant sales increased (+0.02 DDD/TID) while monthly anxiolytic sales decreased (-0.07 DDD/TID). With pandemic onset, there was a relevant and persisting trend increase (+0.20 DDD/TID per month) for antidepressant sales overall, with an estimated excess of 112.6 DDD/TID sold from May 2020 until December 2022. Anxiolytic sales were elevated from February 2020 throughout the pandemic but returned to expected levels by December 2022, with an estimated excess of 33.8 DDD/TID. There was no evident association between stringency and antidepressant or anxiolytic sales., Conclusions: This study showed a protracted trend increase in the consumption of antidepressants since pandemic onset, while increases in anxiolytic consumption were temporary., Clinical Implications: We provide evidence that the COVID-19 pandemic may have had long-lasting consequences on the prevalence and treatment of depression and anxiety disorders, requiring further actions by researchers and policy-makers to address this potential public mental health crisis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)