Trends in antiepileptic drug treatment and effectiveness in clinical practice in England from 2003 to 2016: a retrospective cohort study using electronic medical records

Objective
To assess the evolution of antiepileptic drug (AED) treatment patterns and seizure outcomes in England from 2003 to 2016.


Design, setting and participants
Retrospective cohort study of electronic medical records from Clinical Practice Research Datalink and National Health Service Digital Hospital Episode Statistics databases. Patients newly diagnosed with epilepsy were identified and followed until end of data availability. Three eras were defined starting 1 April 2003 (first National Institute for Health and Care Excellence (NICE) guideline); 1 September 2007 (Standard and New Antiepileptic Drugs publication); and 1 January 2012 (second NICE guideline).


Outcome measures
Time from diagnosis to first AED; AED sequence; time from first AED to first 1-year remission period (no new AED attempts and no seizure-related healthcare events); time from first AED to refractoriness (third AED attempt regardless of reason); Kaplan-Meier analysis of time-to-event variables.


Results
4388 patients were included (mean follow-up: 6.8, 4.2 and 1.7 years by era). 84.6% of adults (≥16 years), 75.5% of children (<16) and 89.1% of elderly subgroup (65+) received treatment within 1 year; rates were generally stable over time. Treatment trends included reduced use of carbamazepine (adult first line, era 1: 34.9%; era 3: 10.7%) and phenytoin, earlier line and increased use of levetiracetam (adult first line, era 1: 2.6%; era 3: 26.2%) and lamotrigine (particularly in adults and elderly subgroup), and a larger number of different AEDs used. Valproate use shifted somewhat to later lines. Rates of 1-year remission within 2 years of starting treatment increased in adults (era 1: 71.9%; era 3: 81.4%) and elderly (era 1: 76.1%; era 3: 81.7%). Overall, 55.5% of patients relapsed after achieving 1-year remission. Refractoriness rates remained stable over time (~26% of adults within 5 years).


Conclusion
Treatment trends often were not aligned with era-relevant guidance. However, our results suggest a slight improvement in epilepsy treatment outcomes over the 13-year period.