Peer-reviewed article
Therapeutic strategies after discontinuation of valproate in females of child-bearing potential with bipolar disorder: an insurance claims database study in France and the United Kingdom.
Sandrine Colas, Juliette Longin, Xinyu Li, Sigal Kaplan, David Bigat et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This medical study examines treatment patterns in females of child-bearing potential with bipolar disorder after stopping valproate, which is unsafe in pregnancy. Using insurance database records from France and the UK, researchers tracked 9,943 and 144 women respectively for one year to see what medications replaced valproate. About two-thirds of women successfully discontinued valproate without restarting it, though treatment patterns varied widely between countries.
Key points
- 66.9% in France and 63.2% in UK successfully discontinued valproate without reintroduction
- 47.9% in France and 51.4% in UK maintained valproate discontinuation at 1-year follow-up
- 32.7% of French women used no bipolar disorder treatment after valproate discontinuation
- Lamotrigine and lithium within 90 days before stopping valproate were associated with successful discontinuation
- Older age, longer bipolar disorder history, and no treatment exposure within 3 months increased risk of returning to valproate
Limitations
This study examines medication prescribing patterns recorded in insurance databases but does not measure children's health outcomes or maternal mental health symptoms. It cannot determine whether alternative treatments were as effective as valproate in preventing mood episodes or protecting child health.
Abstract
Valproate is contraindicated in pregnant women with bipolar disorder (BD) and must not be prescribed to females of child-bearing potential (FCBP) unless complying with the pregnancy prevention programme. This post-authorization safety study aimed to identify the treatment patterns within 1-year following valproate discontinuation in FCBP. The success in BD management after valproate discontinuation was defined as no valproate reintroduction in the follow-up period. FCBP with BD were identified between January 1, 2014, and December 31, 2017, from SNDS (France) and CPRD GOLD (UK) databases and followed up for 1 year. A total of 9,943 (SNDS) and 144 (CPRD) FCBP were included; 66.9% (SNDS) and 63.2% (CPRD) were part of clusters where alternative treatment was considered successful. After valproate discontinuation, 32.7% of FCBP tended to not use any BD-treatment, 25.6% and 8.6% used 1 and 2 BD-treatments, respectively in SNDS; and 22.2%, 14.6%, 10.4%, and 16% of FCBP tended to use 0, 1, 2, and mixed mood stabilizers, respectively, in CPRD. In SNDS, the factors most associated with success were prescription of lamotrigine or lithium within 90-days before index date, dose-tapering phase in 1-year before index date, pregnancy starting in the year before index date. The factors most strongly associated with valproate reintroduction were older age, longer history of BD, and no exposure to a BD-treatment within 3-months after index date. Valproate discontinuation was maintained in 47.9% (SNDS) and 51.4% (CPRD) of FCBP, especially in young women, with stable disease. Decisions on BD treatment in FCBP should consider both maternal mental health and fetal safety.