ImportanceAlthough the COVID-19 pandemic has had a negative impact on mental health, there is no comprehensive longitudinal study of the entire population of a country without selection bias.ObjectiveThe objective of this study was to evaluate the prescription of psychotropic drugs during the COVID-19 pandemic, using data from the French national health data system (SNDS).Design, settings, and participantsPrescriptions for psychotropic drugs (antidepressants, anxiolytics, hypnotics, and antipsychotics) from 1 January 2015 to 30 September 2021 were collected from administrative data provided by the SNDS. This database includes more than 99% of the French population, i.e., 67 million people. The data were analyzed using an interrupted time series analysis (ITSA) model.Main outcomes and measuresConsumption of psychotropic drugs was aggregated in months and expressed in number of boxes per thousand inhabitants.ResultsDuring the study period, more than 1.3 billion boxes of psychotropic medications were dispensed. Comparison of psychotropic drug dispensing before and after the pandemic showed a relative increase of 0.76 (95 CI 0.57 to 0.95, p<0.001) boxes per month per thousand inhabitants, all classes of psychotropic drugs combined. Three classes saw their consumption increase in an almost similar proportion, respectively, by 0.23 (0.15 to 0.32, p<0.001) boxes for antidepressants, 0.27 (0.20 to 0.34, p<0.001) boxes for anxiolytics and 0.23 (0.17 to 0.30, p<0.001) boxes for hypnotics. The change in antipsychotic consumption was very small, with an increase of 0.04 boxes (0.02 to 0.06, p = 0.001) per month per thousand population.Conclusion and relevanceThe COVID-19 pandemic had led to an increase in the consumption of psychotropic drugs, confirming the significant impact of the pandemic on the mental health of the general population.