The adverse event profile of levetiracetam: A meta-analysis on children and adults
Introduction from Dr Markus Reuber, editor-in-chief of Seizure
Seizure 31 has published The adverse event profile of levetiracetam: A meta-analysis on children and adults
It is now sixteen years since the Federal Drug Administration approved levetiracetam as an add-on medication for use in focal epilepsies. Since then the paediatric and adult licenses of levetiracetam have been extended to other types of epilepsy (including generalized seizure disorders) and levetiracetam can now be used on its own in many countries. When this drug first became available, neurologists with a pool of patients with refractory epilepsies were impressed. Here was a drug, which seemed to help control seizures in a significant number of patients who had failed to become seizure-free with other medications. It did not require metabolisation, was excreted renally, rarely caused allergic reactions, had a straightforward pharmacodynamics profile and few relevant drug-drug interactions. Since these early days, good news about levetiracetam has kept coming: it seems to be relatively safe in pregnancy (1), and may well the drug of choice in benzodiazepine-resistant status epilepticus (2). Given that many now consider levetiracetam a safe drug which rarely makes seizure disorders worse and which can be introduced very easily, it is likely to be the first choice of medication for epilepsy which experts tell non-experts to start over the phone, or which doctors may be tempted to introduce when they are not quite certain of the diagnosis.
However, the meta-analysis by Verrotti et al. which is my editor’s choice from the current issue of Seizure reminds us that levetiracetam does have a range of side effects. These even became apparent in the relatively short randomized controlled studies which were included in the analysis. Somnolence, dizziness, nervousness/irritability and asthenia/fatigue are amongst the symptoms reported more commonly by patients taken levetiracetam than by patients in the placebo groups. In clinical practice “irritability” is particularly important because it can be socially disabling and may not be apparent to the patient him or herself (“Who’s angry? – Are you telling me I’m angry?”). Given that this particular manifestation of antiepileptic drug treatment is less of an issue with other AEDs, doctors who are not familiar with levetiracetam may fail to enquire about it (ideally by asking not only the patient but also who live with them). Irritability or difficulties with temper control can pose particular challenges for the doctor, if seizures seem to be controlled. Are the experiential and behavioural changes bad enough to warrant a change of treatment? Is the irritability really due to the levetiracetam or the patient’s problems at home or work?
Even after sixteen years, we have not stopped learning about levetiracetam. Levetiracetam has been a great addition to the toolbox of the practicing epileptologist. However, in the treatment of epilepsy one size does not fit all, and the control of seizures is only as important in the treatment of the disorder as the minimization of side effects.
[1] T Tomson, H Xue, D Battino. Major congenital malformations in children of women with epilepsy. Seizure 2015;28:46–50.
[2] Z Yasiry, SD Shorvon. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: A meta-analysis of published studies. Seizure 2014;23:167-174.
[3}A Verrotti, G Prezioso, F Di Sabatino, V Franco, F Chiarelli, G Zaccara. The adverse event profile of levetiracetam: A Meta-Analysis on children and adults. Seizure 2015;31:49-55.