Use Of Older Antiepileptic Drugs Research Articles

Clinical characteristics of antiepileptic-induced liver injury in patients from the DILIN prospective study

Antiepileptic drugs (AEDs) are a common cause of drug-induced liver injury (DILI). Over the last few decades, several newer AEDs were approved for marketing in the United States, and they are increasingly prescribed for indications other than seizures. Contemporaneous data related to trends and characteristics of AED-related liver injury are sparse. We report the trends, characteristics, and outcomes of patients with AED-related DILI enrolled into the DILIN Prospective Study between 2004 and2020. Among 1,711 participants with definite, highly likely, or probable DILI, 66 (3.9%) had AED-related DILI (lamotrigine [n= 18], phenytoin [n= 16], carbamazepine [n= 11], valproate [n= 10], gabapentin [n= 4], and others [n= 7]). The frequency of AED-related liver injury significantly decreased during the study period (from 8.5% of cases during 2004-2007 to 2.6% during 2015-2020, p= 0.01). AEDs other than phenytoin were commonly prescribed for non-seizure indications. Compared to non-AEDs, patients with AED-related liver injury were younger (mean age 38.5 vs. 50.1 years-old, p <0.001) and more likely African American (27% vs. 12%, p= 0.008). DRESS was common with liver injury caused by lamotrigine, phenytoin, and carbamazepine, but not valproate or gabapentin. Liver injury severity was moderate to severe in the majority: 5 died, and 3 underwent orthotopic liver transplantation (OLT). No patient with lamotrigine-related DILI, including 13 with hepatocellular jaundice, died or needed OLT, while 3 out of 16 patients (19%) with phenytoin-related DILI either died or required OLT. The frequency of AED-related liver injury significantly decreased over the last 2 decades in our experience. AED-related liver injury has several distinctive features, including a preponderance in African American patients and those with immunoallergic skin reactions, with outcomes depending on the type of AED involved. Medications used to treat epilepsy may sometimes cause severe liver injury. However, several new medications have been approved over the last 2 decades and they may not be as toxic to the liver as older antiepileptic medications (AEDs). This study shows that overall liver injury due to AEDs is decreasing, likely due to decreasing use of older AEDs. Liver injury due to AEDs appears to be more common in African Americans and is commonly associated with allergic skin reactions.

O-31 Antiepileptic drug (aed) exposure in pregnancy and pregnancy outcome from national drug usage data

Background Antiepileptic drugs (AEDs) taken during pregnancy are known to increase the risk of fetal malfor-mations and potentially affect the neurodevelopment in children exposed. This study aimed to investigate the use of AEDs by pregnant women and women during their childbearing years in New Zealand and the association between AED use and rates of pregnancy termination, spontaneous abortion and stillbirth. Methods Retrospective population based cohort study using administrative databases in New Zealand between 2008 and 2014. Women who had been pregnant were identified by the National Minimum Dataset and were linked to the Pharmaceutical Collection to obtain infor-mation on use of AEDs. Women aged between 15 and 45 years dispensed AEDs were identified in the Pharmaceu-tical Collection. Results There was a significant increase in the number of women of child-bearing potential prescribed AEDs, from 9 women per 1000 women in 2008 to 11.4 wom-en per 1000 women in 2014. Use of the older generation AEDs declined over the time period while use of the newer generation AEDs increased. General practitioners provided 60% of the prescriptions of AEDs to women of child-bearing potential. Women who had been dis-pensed an AED had an increased rate of spontaneous abortion and pregnancy termination compared to those not dispensed an AED, 13.16 spontaneous abortions per 100 pregnancies, compared with, 8.00 per 100 pregnancies (risk ratio 1.64, 95% CI 1.50 to 1.80), and 21.29 terminations per 100 pregnancies compared with 19.50 per 100 pregnancies (risk ratio 1.09, 95% CI 1.02–1.17). Conclusion Use of newer AEDs is increasing in women of child-bearing potential in New Zealand leading to an overall increase in AED use in this group despite a fall in the use of older AEDs. AED use is this study was associat-ed with an increased risk of spontaneous abortion and increased rate of pregnancy termination.

Utilization of antiepileptic drugs in Israel

The aim of the study was to identify trends in utilization of antiepileptic drugs (AEDs) over time in a nation-wide population in Israel. Data on AED utilization (for all indications) for the period 2010-2014 were obtained from pharmaceutical companies that distribute AEDs in Israel. Prevalence of AED utilization was reported as defined daily doses (DDD)/1000 inhabitants/day. The utilization of most AEDs included in our analysis remained stable over the study period. The greatest increases in utilization of drugs established in Israel were observed for lamotrigine (33%), oxcarbazepine (31%), and primidone (18%). Decreases in use were recorded for carbamazepine (18%) and phenobarbital (15%). Use of older AEDs appeared to be relatively high, compared with the use of newer AEDs. During the study period of 2010-2014, conventional AEDs remained a main treatment choice in Israel, in certain cases in contrast to current recommendations and guidelines, for reasons yet to be revealed in further research.

048 Lost in translation: epilepsy in KwaZulu Natal South Africa

In 2009 based at Mseleni hospital in KwaZulu Natal I was tasked to assess patients with epilepsy and to provide basic seizure education to doctors and nursing sisters in rural...

Long-term use of older antiepileptic drugs can lead to hardening of the arteries

Long-term use of older antiepileptic drugs can lead to hardening of the arteries

Migraine Prophylaxis With Topiramate and Bone Health in Women

Antiepileptic drugs (AEDs) are commonly used for prevention of migraine headaches. Bone loss is a known complication, particularly associated with use of older AEDs. Topiramate is a newer AED, widely used for migraine prevention, but no evidence is currently available on its effect on bone metabolism. In a clinic-based pilot study, we evaluated bone health by examining biochemical and radiological markers of bone metabolism, in women with migraine. Osteopenia was noted in 53% of the patients and was associated with the duration of exposure to topiramate (P = .04).