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Trial Lecture – time and place
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Adjudication committee
- First opponent: Associate Professor Jakob Christensen, Aarhus University and Aarhus University Hospital, Denmark
- Second opponent: Adjunct Professor Eva Kumlien, Uppsala University and Uppsala University Hospital, Sweden
- Third member and chair of the evaluation committee: Professor II Trygve Holmøy, University of Oslo
Chair of the Defence
Professor II Erik Taubøll, University of Oslo
Principal Supervisor
Professor Cecilie Johannessen Landmark, OsloMet
Summary
Epilepsy is a common neurological disease. During recent decades, several new drugs have become available.
The overall aim of this thesis was to evaluate the efficacy and tolerability of four new ASMs - eslicarbazepine acetate (ESL), lacosamide (LCM), perampanel (PER), and brivaracetam (BRV) - in patients with very difficult-to-treat epilepsy. Furthermore, we wanted to assess the importance of pharmacokinetic variability for outcome evaluation.
All six studies in this thesis are based on retrospective observational studies. The clinical data were collected from the patients’ medical records.
All four ASMs studied had a moderate efficacy, with a responder rate (i.e. >50% seizure reduction) varying from 23% to 47%; BRV seemed to be somewhat more superior in efficacy. A persistent seizure-free rate of around 5% was achieved. The drugs seemed to be relatively well tolerated, although 41% of patients stopped treatment with PER due to adverse effects. As expected, the sodium-channel blockers, ESL and LCM, gave rise to neurological adverse effects, such as dizziness and cognitive impairment, whereas PER and BRV were associated with frequent psychiatric adverse effects.
We calculated one-year retention rates for all four drugs, which are: ESL 83%, LCM 73%, PER 51%, and BRV 61%.
We found extensive pharmacokinetic variability (6-14-fold) for all of the study drugs. For all drugs, with the exception of ESL, there was a significant decrease in serum concentrations when used in combination with enzyme-inducing drugs. There was no clear correlation between serum concentrations and efficacy/tolerability for any of the drugs. Based on our results, the reference range for LCM was maintained and ESL was reduced.
All four drugs, ESL, LCM, PER, and BRV, were generally well tolerated in patients with difficult-to-treat epilepsy. There was extensive pharmacokinetic variability. However, the relationship between responders and suggested reference ranges was strengthened.
Additional information
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