The COVID-19 pandemic imposed two lockdowns of eight and six weeks in France. While access to care was reduced during lockdown periods, these stressful situations with the pandemic and lockdown periods may have a negative impact on mental health, especially in vulnerable subgroups. Monitoring of psychotropic drugs consumption in France is a comprehensive and reliable tool for indirectly analyzing the mental health of French people. This historical cohort study (n = 767 147) investigated the short-term and long-term evolution of the weekly trend of psychotropic drugs users in 2020 by performing a Seasonal Trend decomposition time series analysis. Rate of progression of consumers per week increased from 186 in the last week of 2019 to 261 per week in the last week of 2020 (+40.3%). Our results did not show a significant break in psychotropic drugs consumption trends during the year 2020 and its two lockdowns. The increase in trend regarding psychotropic drugs consumptions was greatest in young people (<15 years) and patients not being socially deprived. Despite the increase in consumers with restrictive health measures, the French drugs delivery system has been able to adapt with the support of government and pharmacy network. This point should be kept in mind as the necessary reforms to the health care system are undertaken.The COVID-19 pandemic has a negative impact on mental health and two lockdowns occurred in France with reduced access to care. In this context, monitoring of psychotropic drugs consumption is a comprehensive and reliable tool for analyzing the mental health of French people. We hypothesized that the psychotropic drugs consumption has increased during the 2020 COVID-19 pandemic, testifying to French people mental health deterioration, with psychotropic drugs consumption breaks during lockdowns, especially during the first “grand national lockdown”, due to the closure or difficulties for accessing to health care structures. By carrying out a historical cohort study among Pays de la Loire residents (n = 767 147), we investigated evolution of the weekly trend of psychotropic drugs users in 2020 compared to 2019 by performing a Seasonal Trend decomposition time series analysis. Between 2019 to 2020, we found a + 40.3% rate of progression of consumers per week. During the year 2020, changes in trend regarding psychotropic drugs consumptions was observed in various sub-groups, e.g. greater in the youngest (< 15 years), which may indicate a vulnerable group strongly impacted by COVID-19 negative consequences, and patients not being socially deprived, which may indicate a group with probably an easier access to care. Lockdown periods were not associated with a significant change in psychotropic drug use, suggesting a form of resilience in the French health care system to maintain its capacity to deliver psychotropic treatments. We mainly discussed that despite the increase in consumers and the policies of restricting access to care during lockdown periods, the French drugs delivery system has been able to adapt thanks to supportive policy actions (extension of the prescriptions validity without the need for a renewal by a physician during periods of lockdowns), an efficient pharmacy network with a collaborative practice of health actors that need to be developed and/or conserved to face potential future health crises.