Did advice on the prescription of sodium valproate reduce prescriptions to women? An observational study in three European countries between 2007 and 2016

Abstract

Objectives In November 2014, the CMDh (a regulatory body representing EU Member States) advised doctors not to prescribe sodium valproate for epilepsy or bipolar disorder in preg nant women, in women who can become pregnant, or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if this warning led to changes in prescription patterns. Design and setting Cohort of 5.4 million women aged between 10 and 50 years identified in electronic health care data from United Kingdom, France, and Italy (2007–2016). Main outcome measures Anti‐epileptic drug (AED) prescriptions. Results The prevalence of women receiving AED prescriptions in 2016 varied from 12.2 per 1000 to 29 per 1000 in the four regions. The incidence of prescribing any AED (excluding clonazepam, gabapentin, and pregabalin) fell each year on average by 7.5% (95% CI, 7.0%‐8.0%; Emilia Romagna), 9.6% (8.3%‐11.0%; France), 7.1% (6.7%‐7.6%; Tuscany), and 0.4% (0.2%‐1.0%; United Kingdom). The relative odds of prescribing sodium valproate rather than any other AED decreased more after 2014 compared with before the end of 2014 in France (OR = 0.77; 95% CI, 0.60‐0.98), Tuscany (0.81; 0.76‐0.86), Emilia Romagna (0.83; 0.76‐0.90), and the United Kingdom (0.92; 0.80‐1.06; not statistically significant). Conclusions There is evidence that the CMDh warning did lead to changes in prescription patterns of sodium valproate in women of childbearing age. There were considerable differences in prescribing practice amongst regions of Europe.

Effectiveness of risk minimisation measures for valproate: A drug utilisation study in Europe

“…A meaningful decrease in valproate initiation in France and the UK was also suggested in a study by Charlton et al 16 For Sweden, this decrease was in line with a study by Karlsson Lind et al which found an overall significant decrease of valproate initiations 2 years after the implementation of RMMs in 2015 22 …”

“…Initiation of valproate as second line therapy: proportion of valproate initiations preceded by other medications for valproate indications. Subgroup WCBP; main study periods; incident prescriptions and first-ever prescriptions [Colour figure can be viewed at wileyonlinelibrary.com]A meaningful decrease in valproate initiation in France and the UK was also suggested in a study by Charlton et al16 For Sweden, this decrease was in line with a study by Karlsson Lind et al which found an overall significant decrease of valproate initiations 2 years after the implementation of RMMs in 2015 22. …”

Changes in antiepileptic drug prescriptions over a decade in childbearing women in Lombardy region, Italy

“…Our findings estimate that 14 per 1000 women of childbearing age received at least 1 antiepileptic prescription in 2019. This prevalence is consistent with that observed in other Italian regions (12–18‰), in other European countries (19–29‰), and in New Zealand (11.4‰) 17,20 …”

Valproic acid and socioeconomic associations in Swedish women with epilepsy 2010–2015

“…Our results are in line with previous reports that VPA use is decreasing in women with epilepsy of childbearing age. A large cohort study of VPA prescription in the UK, France, and in Italy used interrupted time series logistic regression found that the odds of being prescribed VPA compared to another AED decreased from 0.94 to 0.72 in France, from 0.87 to 0.80 in the UK, and from 1.05 to 0.85 in Tuscany Italy 11 . A Swedish study used segmented logistic regression analysis and found a negative trend change N = −8.57, p = 0.01 among women with epilepsy aged 0–45 years from 2014 to 2016 14 .…”

“…Food and Drug Administration (FDA) and the European Medicines Agency (EMA), to restrict usage and VPA is now contraindicated for women of fertile age in the European Union unless all conditions of a certain pregnancy prevention program are met. 10 Previous studies have evaluated the effects of the restricted recommendations on the prescription of VPA among fertile women in different European countries [11][12][13][14] and reported coherent findings of decreased use 11,13,14 or ceased increase 12 in VPA prescriptions after 2014. However, previous studies lack analysis of whether the observed decrease in VPA prescription is general or differs among socioeconomic groups.…”