Valproate utilisation trends among women of childbearing potential in Ireland between 2014 and 2019: A drug utilisation study using interrupted time series

Hughes, John E.; Buckley, Niamh E.; Looney, Yvonne; Curran, Sinéad; Mullooly, Maeve; Bennett, Kathleen

doi:10.1002/pds.5427

Cited by 3 publications

(6 citation statements)

References 26 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For comparison, in 2014, the prevalence of VPA use per 1000 women aged 16–44 years in Ireland was approximately 2, but by 2019 it had decreased to approximately 1.5 [ 24 ]. The data of other countries suggest that the monthly prevalence rate of VPA use ranged from 1.9 to 2.2 per 1000 women of reproductive age in Denmark between 2010 and 2020, from 1.6 to 1.2 in the Netherlands and from 3.2 to 1.9 in the UK [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…While the definitions of reproductive age and the calculation methods varied between the studies, most published studies describing trends in the use of VPA have shown that the annual prevalence and incidence of VPA prescribing declined or stabilized after 2014 in women of reproductive age [ 12 , 14 , 16 , 17 , 24 , 26 – 28 ]. In Latvia, a decline in prevalence and incidence of VPA use continued after 2018 as well.…”

Section: Discussionmentioning

confidence: 99%

“…Several published studies evaluated the impact or effectiveness of RMM in 2014 on VPA use in the EU [ 14 , 15 , 17 , 24 – 26 , 29 – 31 ]. The methods differ between the studies, making direct comparison difficult; however, the 2014 RMMs have had a positive impact on incident prescriptions, VPA prescribing rates, VPA initiations as second-line therapy, incidence of VPA-exposed pregnancies and the use of effective contraception by patients in many countries [ 14 , 17 , 26 , 29 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of Risk Minimisation Measures on Valproate Use among Women of Reproductive Age in Latvia Between 2013 and 2020: A 7-Year Nationwide Prescription Database Study

Rutkovska,

Seilis,

Neikena

et al. 2023

Drugs - Real World Outcomes

View full text Add to dashboard Cite

Background A relevant safety concern for the use of valproate (VPA) in women of reproductive age is its teratogenicity. In 2014 European Medicines Agency (EMA) introduced risk minimisation measures (RMMs) to reduce the VPA use by women of reproductive age, where the impact on VPA use was not as large as expected. In 2018, the EMA introduced additional RMMs, and it is essential to assess impact of these interventions. Objective The objective of this study was to evaluate the impact of the EMA-published RMMs in 2014 and 2018 on the prevalence of VPA use and to describe trends in the prevalence rate and incidence proportion of VPA use in epilepsy, bipolar disorder and off-label indications in Latvia. Methods This was a nationwide population-based study using a primary care prescription database. The study included women in age groups < 15, 15–49 and > 49 years and men in age group 15–49 years who have received VPA. This study assessed the prevalence rate and the incidence proportion of VPA use. The impact of RMMs on the two study intervention periods [fourth quarter (Q4) 2014 and Q4 2018] in men and women was evaluated using causal impact analysis. Results In the study cohort, VPA use in women in the age group 15–49 years decreased after the first and second intervention periods, where after the first intervention period the relative reduction in prevalence of VPA consumption was −7.7 [95% confidence interval (CI) −10%, −5.1%] and after both study periods −6.4% (95% CI −11%, −1.5%). In girls < 15 years of age, valproate use decreased after both intervention periods, while in women > 49 years old VPA use increased. In men aged 15–49 years, an increase after the first period and a non-significant decrease after both intervention periods was observed. The prevalence of valproate use in girls < 15 years and women 15–49 years of age with bipolar disorder, epilepsy and off-label indications decreased per 1000 people during the study period. The incidence proportion of VPA use in women aged 15–49 years decreased each year since the beginning of the study period. Conclusions A statistically significant decrease in the prevalence of VPA use was identified among girls < 15 years and women 15–49 years of age. In Latvia, an overall good reaction to the EMA RMMs was observed. The effects go beyond the target population and affect the use of VPA in young girls as well. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-023-00394-y.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Risk Minimisation Measures on Valproate Use among Women of Reproductive Age in Latvia Between 2013 and 2020: A 7-Year Nationwide Prescription Database Study

Rutkovska,

Seilis,

Neikena

et al. 2023

Drugs - Real World Outcomes

View full text Add to dashboard Cite

show abstract

“…Similarly, the World Health Organization has recommended against the use of valproic acid in women of childbearing potential and recommended the use of contraception if valproic acid is used. 16,17 Several studies in the US and Europe [18][19][20][21][22] have shown a decreasing trend in valproic acid use among persons of childbearing potential after the implementation of enhanced risk minimization efforts. In recent work, Al-Bahou et al 23 noted that the rate of decrease appears to vary across indications for valproic acid use.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies in the US and Europe 18 , 19 , 20 , 21 , 22 have shown a decreasing trend in valproic acid use among persons of childbearing potential after the implementation of enhanced risk minimization efforts. In recent work, Al-Bahou et al 23 noted that the rate of decrease appears to vary across indications for valproic acid use.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Exposure to Valproic Acid Across Various Indications for Use

Smolinski,

Sarayani,

Thai

et al. 2024

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceTeratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced warnings or implemented risk minimization programs to reduce exposure during pregnancy.ObjectivesTo determine pregnancy rates during valproic acid use and concomitant contraception use across indications.Design, Setting, and ParticipantsThis retrospective cohort study used data from the Merative MarketScan commercial claims databases from January 1, 2005, to December 31, 2020, to identify female patients aged 12 to 44 years who initiated valproic acid treatment and had continuous insurance enrollment 6 months before initiation and 9 months after treatment end. A treatment episode included consecutive prescription fills that occurred within 7 days from the end of the days’ supply of the previous dispensing. Data were analyzed from March 1 to September 10, 2023.Main Outcomes and MeasuresTreatment episodes were categorized by inferred indication using diagnoses preceding treatment initiation, including epilepsy, migraine or headache, mood disorders, and unknown or off-label uses. Pregnancy incidence rate ratios (IRRs) were calculated and were adjusted for age and calendar year. Contraceptive use (prescription contraceptives, intrauterine devices, and implants) during treatment was examined.ResultsThe cohort included 165 772 valproic acid treatment episodes among 69 390 women (mean [SD] age, 29.8 [10.0] years). Mood disorders (42.5%) were the most common indication, followed by migraine or headache (20.1%), with epilepsy playing a minor role (14.9%). Pregnancy incidence rates during valproic acid use remained unchanged, with a rate of 1.74 (95% CI, 1.14-2.53) per 100 person-years in 2005 and a rate of 1.90 (95% CI, 1.16-3.12) per 100 person-years in 2019. Compared with epilepsy, pregnancy rates were more than double for mood disorder (IRR, 2.16 [95% CI, 1.93-2.42]) and migraine or headache (IRR, 2.01 [95% CI, 1.92-2.09]). Few treatment episodes coincided with contraceptive use (37 012 [22.3%]), and oral dosage forms were the most common (27 069 [73.1%]).Conclusions and RelevanceIn this cohort study of patients of childbearing age who used valproic acid, pregnancy rates during valproic acid use did not decrease despite enhanced US Food and Drug Administration safety communications, and contraception use remained low. Patients with migraine and mood disorders accounted for the largest proportion of valproic acid use and had the highest pregnancy rates, while patients with epilepsy had the lowest. These findings suggest a need to enhance efforts to mitigate prenatal exposure to valproic acid, especially for indications where the risk of use during pregnancy outweighs the benefit.

show abstract

Valproate utilisation trends among women of childbearing potential in Ireland between 2014 and 2019: A drug utilisation study using interrupted time series

Hughes

Buckley²,

Looney³

et al. 2022

Pharmacoepidemiology and Drug

Self Cite

View full text Add to dashboard Cite

Purpose: This study aimed to examine trends in valproate use among women of childbearing potential (WCBP) aged 16-44 years in Ireland following two Europeandirected regulatory interventions in December 2014 and April 2018. Methods: This was a repeated cross-sectional study using monthly national pharmacy claims data, to examine trend changes in the prevalence of valproate use among WCBP pre and post two separate regulatory events in December 2014 and April 2018. Annual population estimates from the Central Statistics Office were used to calculate the prevalence rate per 1000 eligible women. Segmented regression analysis of interrupted time series with negative binomial regression was used to examine rates for WCBP aged 16-44 years, and by 10-year age groups. Prevalence ratios (PR) are presented with 95% confidence intervals (CIs).

show abstract

Valproate utilisation trends among women of childbearing potential in Ireland between 2014 and 2019: A drug utilisation study using interrupted time series

Cited by 3 publications

References 26 publications

Impact of Risk Minimisation Measures on Valproate Use among Women of Reproductive Age in Latvia Between 2013 and 2020: A 7-Year Nationwide Prescription Database Study

Impact of Risk Minimisation Measures on Valproate Use among Women of Reproductive Age in Latvia Between 2013 and 2020: A 7-Year Nationwide Prescription Database Study

Prenatal Exposure to Valproic Acid Across Various Indications for Use

Valproate utilisation trends among women of childbearing potential in Ireland between 2014 and 2019: A drug utilisation study using interrupted time series

Contact Info

Product

Resources

About