Examination of the prescription of antiepileptic drugs to prenatal and postpartum women in Japan from a health administrative database

Abstract

Purpose: To evaluate the prevalence and patterns of prescriptions of antiepileptic drugs (AEDs) to prenatal and postpartum women in Japan using a large administrative database.Methods: The dates of pregnancy onset and delivery were estimated using published algorithms and infant birth months. The prevalence of prescribed AEDs, the maximum dose of some AEDs, and the frequency of potential combination therapy with AEDs were evaluated for the 180 days before pregnancy onset, during pregnancy, and at 180-day postpartum.Results: In total, 33 941 pregnant women were eligible for analysis. At least one AED was prescribed to 225 women (66 per 10 000 deliveries) between 180 days before pregnancy and 180-day postpartum and for 135 women (40 per 10 000 deliveries) during pregnancy. The prevalence of AED prescription declined during the first and second trimesters and increased in the third trimester and postpartum. Valproate was the most frequently prescribed drug, followed by clonazepam, lamotrigine, and carbamazepine. Nine (18.4%) of the 49 women with at least one prescription record of valproate in the first trimester were prescribed more than 600 mg/day of valproate.Concerning potential combination therapy, 40 (12 per 10 000 deliveries) concurrently received two or more AEDs between 180 days before pregnancy and 180-day postpartum, respectively, 31 (9 per 10 000 deliveries) women received these drugs during pregnancy.Conclusions: Various AEDs were prescribed to pregnant Japanese women. Women of reproductive age should select the appropriate AED before becoming pregnant, depending on the risk benefit profile.

Folic acid prescribed to prenatal and postpartum women who are also prescribed antiepileptic drugs in Japan: Data from a health administrative database

“…Standardized disease classifications and anonymous record linkages were used in the database (Kimura et al, 2010). Further details of the database have been previously reported (Ishikawa, Obara, Nishigori, Miyakoda, Ishikuro, et al, 2018; Ishikawa et al, 2019). This study was approved by the Institutional Review Board of Tohoku University School of Medicine on July 19, 2016 (Registration No.…”

“…It consisted of 3,836,202 men and women covered by health insurance between January 2005 and August 2016 and comprised ~3% of the population of Japan (Figure 1). Information was collected for women who met the same eligibility criteria as those of a previous report (Ishikawa et al, 2019). Mothers were considered if their infants were covered by the same health insurer during their birth month so that the month and year of birth could be identified.…”

“…The pregnancy onset and the delivery date were estimated using previously described algorithms (Ishikawa et al, 2019; Ishikawa, Obara, Kikuchi, et al, 2020) that were developed based on the findings from health administrative data in a university hospital (Ishikawa, Obara, Nishigori, Miyakoda, Ishikuro, et al, 2018) due to their absence in the Japanese claims database.…”

“…They provide accurate medication dispensing data derived from prescription claims. They also eliminate recall bias and accurately reflect actual clinical practice (Daw, Hanley, Greyson, & Morgan, 2011; Huybrechts, Bateman, & Hernández‐Díaz, 2019; Ishikawa, Obara, Nishigori, Miyakoda, Ishikuro, et al, 2018; Ishikawa et al, 2019). In our previous study, we used a large administrative database to assess the prevalence and timing of AED prescription between 180 days before pregnancy onset and 180 days postpartum.…”

“…At least one AED was prescribed to 225 of 33,941 women (0.66%) during the aforementioned time interval. Valproate was the AED of choice in Japan (Ishikawa et al, 2019). It has been strongly associated with increased risks of NTDs, followed by carbamazepine; however, there is limited evidence of this association with other AEDs (Japanese Society of Neurology, 2018; Werler et al, 2011).…”