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

Abstract

ObjectivesTo review prescribing practice concerning valproate, an established human teratogen, for the management of bipolar disorder in women of childbearing age.DesignThe Prescribing Observatory for Mental Health conducted a baseline clinical audit in the UK, as part of a quality improvement programme.ParticipantsSix hundred and forty-eight clinical teams from 55 mental health Trusts submitted retrospective treatment data relating to patients with a diagnosis of bipolar disorder.ResultsOf the audit sample of 6705 patients, 3854 were 50 years of age or younger. Valproate was prescribed for 24% of women and 43% men in this age group, and the mean dose of valproate was lower in women (1196 mg) than in men (1391 mg). For only half of such women was there documented evidence that information had been provided on the risks for the unborn child and the need for adequate contraception. Valproate was more often used in men to treat mania and aggression, while the most common treatment targets in women were hypomania and relapse prevention.ConclusionsDespite explicit recommendations in national treatment guidelines and published safety alerts and warnings regarding the use of valproate in women of childbearing age, current prescribing of this medication to such women in the context of the treatment of bipolar disorder falls short of best practice, particularly with regard to provision of information regarding the risks associated with exposure to valproate during pregnancy. While women younger than 50 years of age were less likely to be prescribed valproate than men in the same age group, and at a lower dosage, it is unclear to what extent this reflects clinicians’ concerns about teratogenicity or is driven by perceptions of the indication for valproate, and the dosage required, for the treatment of different phases of the disorder in men and women.

Valproate utilisation trends among girls and women from 2013 to 2018

“…A similar study on the population of Stockholm found no influence of the intervention for girls and women being initiated on valproate except the group aged under 45 and diagnosed with psychiatric disorders [18]. While sporadic study results are contrasting and often consist of prevalent use comparison, the strengthened warning by EMA in 2014 was overridden by a stricter regulation in 2018 after a new review process, thus indicating possibly insufficient prior action to reduce valproate prescriptions in European health systems [17][18][19]23,33].…”

Risk management of teratogenic medicines: A systematic review

“…Secondly, it is one of the most cost-effective acne treatments used by patients from different age groups including women of childbearing age (Algoblan et al, 2019;Bérard et al, 2007;Honein et al, 2004). By contrast, it was observed that there were fewer publications on medications prescribed under more recent risk management programmes such as thalidomide, lenalidomide, and valproic acid (Atturu & Odelola, 2015;Brandenburg et al, 2017;Castaneda et al, 2008;Chave et al, 2001;Gotlib et al, 2016;Mulryan et al, 2018;Paton et al, 2018), indicating a need for further investigation of the safety of these medications in terms of adherence to risk management measures for such medications. Good practice guidance suggests that ensuring safe use of medications can have a number of positive effects on treatment outcomes.…”

“…One factor could be the data sources used by the different studies. Some studies relied on medical records as their source of data (Atturu & Odelola, 2015;Bhakta et al, 2015;Cheetham et al, 2006;Crijns et al, 2012;Force et al, 2012;Fritsche et al, 2011;Gotlib et al, 2016;Hayward et al, 2016;James et al, 2007;Langan et al, 2013;Martin et al, 2008;Mody, Farala, et al, 2015;Mulryan et al, 2018;Paton et al, 2018;Pinheiro et al, 2013;Raguideau et al, 2015;Ruiter et al, 2012;E. B. Schwarz et al, 2010;E.…”

Prescribing in pregnancy and breastfeeding

“…It even returned to black triangle status so that intensive monitoring could be carried out. This monitoring led to the banning of prescribing valproate in women and girls of child bearing age unless a pregnancy prevention programme is in place in early 2018 after the publication of findings and of audits took place (Paton, Cookson, Ferrier, Bhatti, Fagan and Barnes 2018).…”