Purpose: To evaluate the change in the number of female valproate users in Lithuania from 2013 to 2018 and determine the presumed impact of two distinct European Medicines Agency (EMA) regulatory interventions on the observed trend.
Method: An interrupted time series analysis was performed using reimbursement data from the National Health Register Fund to detect changes in user trends after a selected regulatory event in time.
Results: The absolute number of female patients under 50 using valproate is seen decreasing over time. After an EMA regulatory procedure in 2014, there was only a delayed decrease in female valproate users under 15 (a change in trend of -4.83, 95%CI = -9.45 to -0.22, P = 0.041, a decrease in level 15 months post-intervention of -40.06, 95%CI = -79.26 to -0.86, P = 0.046). An increase in new prescriptions for patients with epilepsy was noted post-intervention (change in trend 13.75, 95%CI = 6.03-21.48, P = 0.004). The EMA referral procedure in 2017-2018 was followed by a lasting decrease in female valproate users of reproductive age and older (level effect 3 months post-intervention: -201.28, 95%CI = -310.61 to -91.96, P = 0.001 and -170.60, 95%CI = -287.73 to -53.48, P = 0.007, respectively). However, the rate of new initiations on valproate for patients with either epilepsy or mood disorders remained constant.
Conclusions: The number of female patients under 50 using valproate is decreasing over time. The 2018 EMA referral procedure was followed by a notable reduction in female valproate users.
Keywords: Epilepsy; European medicines agency; Interrupted time series; Mood disorders; Valproate.
Copyright © 2019. Published by Elsevier Ltd.