LAUSR

BACKGROUND Liver injury is an important identified risk for agomelatine and several measures were put in place to prevent and minimize such risk. The study aims to assess the impact of four interventions on the incidence of agomelatine use, particularly among patients aged ≥75 in Spain between 2011 and 2018. METHODS Quasi-experimental interrupted time-series analysis to examine data from a nationwide electronic healthcare record database (BIFAP). Quarterly cumulative incidence of agomelatine use per 100 000 patients was calculated and the impact of four regulatory interventions quantified. RESULTS The incidence of agomelatine use decreased by 85% and 87% from 1st quarter 2011 to last quarter 2018 in patients below and above 75 years old respectively. Regulatory actions taken were not associated with an immediate and significant falling level of use or slope. The incidence was less than expected 6 months after the first and third intervention for patients below and above 75 years old, and more than expected after the second and fourth intervention for both populations, though these analysis were underpowered to observe significant results. The downward trend became less pronounced, reaching a residual level of use which remained stable in the last segment of the study period. CONCLUSION New users of agomelatine decreased throughout the study period, starting before interventions took place. The effect of specific interventions might be masked by the progressive decrease tendency, constant over the study period. The effects of external factors that might overlap, unintended consequences and issues concerning statistical modeling in situations where rates are already falling, should be considered when interpreting the results. This article is protected by copyright. All rights reserved.