LAUSR

For a chronic disease such as epilepsy, management of seizures often involves lifelong medication use. The choice of antiseizure medication (ASM) prescribed to patients of childbearing age is important as patients are not always aware of when they will become pregnant; therefore, fetal exposure may not be avoidable. ASMs are also used for conditions other than epilepsy, thus the distribution of use may vary according to indication as management of non-epilepsy conditions may not be similar. Determining the ideal ASM target doses for a patient often involves identification of the concentration that balances seizure control and adverse events, thus maximizing efficacy whilst minimizing fetal exposure to drug. The primary aim of the study by Clavenna et al. was to examine the prescribing trends of ASMs in women of childbearing age and pregnant women in the Lombardy region of Italy. Data from four local health units were collected between 1 January 2010 and 31 December 2019, which included three databases containing outpatient drug prescription information, hospital discharge and birth certificates. Patient data from drug prescription and hospital discharge databases were matched using unique alphanumeric codes associated with every patient. The inclusion criterion for determination of the overall prevalence of ASM use was at least one prescription of an ASM during the study period with an ASM defined according to the N03A subgroup of the Anatomical Therapeutic Chemical (ATC) classification system. Women of childbearing age were defined as those women of ages 15–49 years, the age range mirroring the ages of women who gave birth in the authors' dataset. Men belonging to the same age group were included to provide a comparison control group. Several comparisons were made with the combined databases to understand the prevalence of ASM prescriptions in different groups. In women of childbearing age in 2019, approximately 15% received at least one ASM with a similar prevalence of use over the whole study period. The most frequent ASMs identified were pregabalin, valproate, topiramate and levetiracetam, ranging from 22.3% to 13.1%. In comparison to 2010, the prescription of valproate decreased by approximately 10% by 2019. This decreased trend in valproate use has been reported in other countries. For example, a nationwide outpatient study that included approximately 5.3 million permanent residents of Finland reported a decline in the use of valproate in women of child-bearing age. Interestingly the distribution of ASMs was similar in men except for topiramate, which was present in only 3.9% of men compared to 13.3% of women. It is well known that ASMs are used for multiple indications. It is difficult to speculate the distribution of ASM use since data pertaining to indication for each prescription was not reported in this study. Pregabalin, for instance, is classified as an ASM, but it is also indicated for neuropathic pain. Pregabalin is usually not reported as the most frequently prescribed medication in treating epilepsy patients. How a drug is used (as needed vs. every day) and what doses are used can vary across indications and can affect overall cumulative fetal exposure. The increased use in women compared to men of topiramate could reflect its use for migraine and not epilepsy since migraine has shown to be more prevalent in women. Initial and maintenance treatment of conditions with topiramate is not the same, thus it is difficult to predict overall fetal exposure without more information on the indication for ASM use. Additionally, the study does not provide data on the duration of ASM therapy. The decision to use only a single dispensing of ASM may skew results as it includes patients who may try a medication and discontinue it for lack of effectiveness. Including only women who received multiple months of therapy may have been useful as an indicator of chronic therapy. Additional criteria from hospital records were used in the Clavenna et al. study to determine ASM use during pregnancy as each participant needed to have evidence of giving birth, providing confirmation of a pregnancy. Use of ASM was determined at two time points: 12 and 24 months prior to birth, the 12-month period before birth being an indicator of fetal exposure. It appears that in 2019, only Received: 31 January 2022 Revised: 2 September 2022 Accepted: 18 September 2022