Valproate use in women aged 15–44 years: an observational study in general practice

Abstract

BackgroundValproate is a known teratogen. In April 2018, the Medicines and Healthcare products Regulatory Agency (MHRA) restricted use in women and banned use in pregnancy, except for epilepsy with no other effective treatment. To date, there is limited information on valproate prescribing within primary care.AimTo characterise valproate prescribing to women of childbearing age, recorded advice or general practitioner prescribed contraception and recorded pregnancies.Design & settingA cross-sectional study of patients from all 141 general practices across three Clinical Commissioning Groups in East London.MethodWomen aged 15-44 years prescribed valproate between 1/10/2017-1/1/2020 were included. Exclusion criteria were early menopause, sterilisation procedures or hysterectomy. Pseudonymised data on valproate indication, pregnancy, pre-conception and contraception advice were retrospectively extracted from general practice consultation data. Data were analysed by quarter using univariate statistics.ResultsOf the total 1,042,463 registered patients, 344 women aged 15–44 years were prescribed valproate during the study period; 14 were excluded. There were 10 pregnancies during possible valproate exposure; one was terminated. During the study period, the number of women prescribed valproate significantly decreased (P=0.003). The pregnancy rate decreased from 9.9/1000 on valproate before the MHRA April 2018 warning, to an average of 2.8/1000 afterwards. Recorded pre-conception/contraception advice increased by 79%, from 24% to 43%, of women prescribed valproate.ConclusionWith continued pregnancies in women aged 15-44 years prescribed valproate, patient education and foetal outcomes remain ongoing concerns. Further improvements are needed to ensure women make informed reproductive choices and safeguard future pregnancies from valproate exposure.

Valproate pregnancy prevention scheme: what are the barriers to enrolling patients and how do we meet them?

“…In line with other studies, the demographic distribution of patients on valproate treatment is significantly skewed to the older patient population and the prescription prevalence of valproate in women is known to have been falling over several years, especially for epilepsy 17–22…”

Perampanel for the treatment of patients with myoclonic seizures in clinical practice: Evidence from the PERMIT study

“…Valproate has been used to treat JME, Lennox-Gastaut syndrome, Doose syndrome, myoclonic absence, photomyoclonic epilepsy, eyelid myoclonia with absence seizures, and post-anoxic myoclonus, and has the advantage of being available in an intravenous formulation for use in myoclonus status epilepticus [5]. However, the use of valproate is affected by its well-established teratogenicity, causing congenital malformations and neurodevelopmental delay, severely limiting its use in females of childbearing potential [41,42]. Levetiracetam was effective in treating myoclonic seizures in placebo-controlled trials [7,43] and open-label studies [44][45][46], and is licensed in Europe for the adjunctive treatment of myoclonic seizures in adults and adolescents aged ≥12 years with JME [9].…”

The valproate prescription pattern for female mental healthcare users of reproductive age

“…The drug valproate is used both as an antiepileptic and a mood stabiliser, with increasing use for conditions other than epilepsy, 1 its main use in the field of psychiatry being for bipolar disorder. 2 , 3 It has also been used in other psychiatric disorders to augment the treatment of schizophrenia and borderline personality disorder. As a monotherapy, it is as efficacious as antipsychotics and lithium as a mood stabiliser, but in combined use with antipsychotics has more efficacy than either drugs alone.…”

“…Despite these guidelines, the use of valproate in females of childbearing age, particularly in the treatment of bipolar disorder, has continued to increase in some studies and remains unchanged in others. 2 , 7 , 10 , 22 …”

“… 23 More recent international studies making comparisons before and after the MHRA guideline noticed a decrease in valproate exposed pregnancies and valproate prescriptions in the population of interest, and an increase in preconception advice and use of contraception in those using valproate. 2 , 3 , 6 This study therefore aimed to determine the prescription pattern and adherence to the prescriber guidelines for the use of sodium valproate among females of reproductive age with mental illness at a psychiatric hospital in KwaZulu-Natal (KZN) province, South Africa.…”