Medications containing valproate are used mainly for the treatment of epilepsy. They are less frequently used to treat manic episodes and rarely for migraine. Babies born to mothers who have taken valproate during pregnancy have a higher risk of birth defects and problems with development and for this reason, regulatory authorities took steps to prevent the use of valproate during pregnancy in 2018.
This study will look at prescribing patterns with valproate in the UK before and after these steps were taken to see if they were successful. We will look specifically at valproate prescribing in women of child-bearing potential to see if prescribing complies with updates to prescribing guidance. We will also look for any evidence of usage of effective contraception and at instances of pregnancy occurring whilst valproate is being used. It is possible that the usage of alternative treatments could also have changed as a result of the regulatory action and so we will also look at prescribing patterns for alternative treatments for epilepsy in women of child bearing potential and pregnant women. We will also attempt to infer reasons for valproate discontinuation.
The aim of this study is to evaluate the impact of regulatory action taken in 2018 to prevent pregnancy in women taking valproate medication. We will measure the prevalence and incidence of valproate use amongst women of child bearing potential between 2010 and 2020 using Poisson regression and stratified by age group and most likely indication for valproate use (epilepsy, bipolar disorder and migraine), based on recorded diagnoses. We will determine whether prescribing patterns changed in 2018, using an interrupted time series (ITS) design with segmented Poisson regression. We will assess whether prescribers have been adhering to newly introduced prescribing recommendations for valproate, by looking for evidence of pregnancy testing, contraceptive use and pregnancy occurrence in women receiving valproate, again contrasting the time before and after the action taking in 2018, using ITS analysis. We will also attempt to ascertain where possible, reasons for valproate discontinuation before and after the regulatory action (e.g. pregnancy, desire to become pregnant, adverse drug reaction), and usage patterns for alternative medications that patients may have been switched to or have initiated instead of valproate. Overall, we will be able to make conclusions about the effectiveness of the regulatory action, in terms of prescribing and pregnancy prevention behaviour, and ultimately in terms of numbers of women who become pregnant whilst receiving valproate.
Contraceptive use (hormone based user dependent methods, user independent non-permanent methods and user independent permanent methods); Pregnancy; Reasons for Medication Discontinuation; Pregnancy Testing
Kevin Wing - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Jeremy Brown - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Ian Douglas - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Jeremy Brown - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
CPRD Mother-Baby Link;HES Admitted Patient Care;ONS Death Registration Data;Pregnancy Register