Levetiracetam vs. brivaracetam for adults with refractory focal seizures: A meta-analysis and indirect comparison
Introduction from Dr Markus Reuber, editor-in-chief of Seizure
Research related Levetiracetam (LEV) has featured previously as my Editor’s Choice because this relatively recent addition to the epilepsy treatment tool kit has become a drug of first choice in many different treatment scenarios. Thanks to its wide spectrum of anticonvulsant activity, its relatively high and rapid anti-seizure effects, favorable pharmacokinetic profile, low risk of drug-drug interactions and moderate potential to cause side-effects the efficacy / tolerability balance for LEV has, arguably, looked better than for all other antiepileptic drugs. The most frequent problem with LEV (other than lack of efficacy) which causes patients to abandon treatment with LEV in my practice is mood change, increased aggression or snappiness.
Brivaracetam (BRV) has recently been made available as an add-on antiepileptic drug treatment for the treatment of focal and secondary generalised seizures in several countries around the world. It does not only have a similar name to Levetiracetam, as far as we know, it also uses the same mode of action: binding to synaptic vesicle protein 2a (SV2A) located in presynaptic membranes and regulating the calcium-dependent release of neurotransmitters into the synaptic gap. In this respect BRV, is a more potent drug; it binds reversibly and selectively to SV2A with a 15- to 30-fold higher affinity than LEV . However, to date it is uncertain whether this theoretically favorable pharmacological feature will translate into clinical benefits, such as greater efficacy, a more rapid onset of action, or fewer side effects than LEV. Unfortunately, sufficiently powered studies directly comparing LEV and BRV are, so far, lacking.
My editor’s choice from this issue of Seizure, the indirect comparison of the efficacy and side-effect profile of LEV and BRV by Lin et al. (2) based on 13 placebo controlled, double blinde, randomised controlled trials (RCTs) involving 1765 patients taking LEV and 1919 on BRV provides the best sort of assessment of the relative performance of these two drugs possible at the moment. Somewhat dishearteningly, the conclusion they come to is that there are no significant differences in the measured treatment outcomes between LEV and BRV. If anything LEV looks a little more effective and less likely to cause dizziness. Careful observation of outcomes of “real life” treatment with BRV (in a wider population than those meeting the recruitment criteria for RCTs) will need to demonstrate whether this drug has a important role in the routine treatment of people with epilepsy or not.
(1) Gillard M, Fuks B, Leclercq K, et al. Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. Eur J Pharmacol 2011; 664:36-44.
(2) Lin Zhang, Shaoping Li, Hua Li, Zou Xiaoyi. Levetiracetam vs. brivaracetam for adults with refractory focal. seizures: A meta-analysis and indirect comparison. Seizure 2016; 39:28-33.
(3) Bucher HC, Guyatt GH, Griffith LE, et al. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997; 50:683-91.