Valproate Prescribing in Women of Childbearing Age: An Audit of Clinical Practice

Abstract

Background. Evidence is accruing regarding the risks of valproate exposure in women of childbearing age. Recommendations have recently been made for a higher standard of prenatal counselling and prescribing practice in respect of valproate use in this patient group.Aim and Method. A reaudit was carried out to review the standard of clinical discussion around teratogenic risk and pregnancy planning offered to women of child-bearing age prescribed valproate. Case notes and prescription charts of women 45 years old or less were examined and compared with the results of a previous audit in 2005.Results. The use of valproate was increased overall by 64% and there was an 18% increase in off-label valproate use. The rate of clinical discussion carried out during commencement declined from 70% to 35% and at annual review from 50% to 22%. There was less clinical discussion in outpatients and in older patients. More than 40% of doctors surveyed were not confident about giving information to women.Clinical Implication. There is a need for a multidisciplinary approach and action at Healthcare Trust level, to increase awareness and reduce risks associated with valproate prescribing in childbearing women.

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

“…A further weakness was that for three databases, it was not possible to determine the indication for prescribing, partly related to the increasing number of indications for which AEDs are now prescribed and an increase in the extent of off‐label prescribing . A study in the United Kingdom, using electronic health care data, found that 62% of prescriptions issued for pregabalin between 2004 and 2009 did not have a diagnosis code corresponding to one of the approved indications .…”

“…In the A further weakness was that for three databases, it was not possible to determine the indication for prescribing, partly related to the increasing number of indications for which AEDs are now prescribed 1,2,26 and an increase in the extent of off-label prescribing. 27 A study in the United Kingdom, using electronic health care data, found that 62% of prescriptions issued for pregabalin between 2004 and 2009 did not have a diagnosis code corresponding to one of the approved indications. 28 The pattern of medications prescribed, particularly the increases in gabapentin and pregabalin, indicates that much of the increase in prescriptions was due to non-epilepsy indications, particularly pain treatments.…”

A UK clinical audit addressing the quality of prescribing of sodium valproate for bipolar disorder in women of childbearing age

“…The association between valproate and congenital malformations is clearly dose-related in the treatment of epilepsy; analysis of data from just over a thousand valproate-exposed pregnancies on the EURAP registry (European Registry of Antiepileptic Drugs and Pregnancy) revealed that the rate of congenital malformations identified by 1 year of age was 5.6% when the daily dose of valproate was less than 700 mg at conception, 10.4% when the dose was between 700 and 1499 mg, and 24.2% when the dose was 1500 mg or higher. 6 A further prospective observational study of 1220 women exposed to valproate monotherapy during pregnancy reported an MCM prevalence of 5% by 6 weeks of age with a daily dose of 600 mg or less, 6.1% with a daily dose of 600–1000 mg and 10.4% with a daily dose higher than 1000 mg. 7 The Medicines and Healthcare products Regulatory Agency 18 has concluded that while the teratogenic potential of valproate is greatest at higher doses, which they define as being above 1000 mg daily, the available data do not allow for the identification of a threshold dose of valproate, below which there is no teratogenic risk.…”

“…This is double the proportion of women reported to have received this information in the local clinical audits by James et al 15 and Wieck et al 16 mentioned above, and a third higher than that found in another, more recent audit in the UK. 18 When considered together, there is some evidence from these independent clinical audits that practice with respect to informing women about the risks associated with valproate treatment is improving over time, but absolute adherence to our clinical practice standard remains disappointing given the high profile warnings from NICE, 1 the EMA 12 and, jointly, the MHRA and NHS Improvement. 20 A QIP conducted within South London and Maudsley NHS Foundation Trust between 2008 and 2009 reported a sixfold increase in the proportion of women informed about the teratogenic potential of valproate from one in ten to almost two-thirds.…”

Sodium valproate in pregnancy: what are the risks and should we use a shared decision-making approach?

“…Sodium valproate is a medication licensed for both epilepsy [ 7 ] and bipolar disorder [ 8 ], and is also used off label for a range of indications including migraine prophylaxis [ 5 ]. Whilst its use in epilepsy is falling in the UK as the use of third-generation anticonvulsants increases [ 9 , 10 ], its use for bipolar disorder has been increasing, especially among women of childbearing age [ 11 ]. In Ireland, recent data corroborate these findings [ 12 ], which necessitate increased surveillance and an improved understanding of alternatives [ 13 ].…”