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Substitution Monotherapy with Levetiracetam vs. Older Antiepileptic Drugs, a Randomized Comparative Trial02/15/2013
In the December issue of the journal, Archives of Neurology, Doctors Hakami and colleagues from the faculty of medicine in Jazan University in Saudi Arabia and the Department of Medicine at the University of Melbourne, and Department of Neurology in the Melbourne Psychiatric Center in the Royal Melbourne Hospital present an analysis to determine whether patients who have failed their first antiseizure drug (AED)—that is seizures persisted despite taking the medication--, have better neuropsychiatric and quality of life outcomes if the second drug is switched to levetiracetam taken by itself, compared to a second older antiepileptic drug, such as phenytoin, carbamazepine or valproic acid.
This randomized comparative trial, included patients who had partial epilepsy and had failed sole therapy with phenytoin, carbamazepine or valproate, and were randomized to monotherapy with levetiracetam or one of the older antiepileptic drugs. Assessments were performed at baseline, three months and 12 months using questionnaires that looked at neuropsychiatric outcomes, quality of life, seizure control, side effects from the drug, and neurocognitive outcomes. This was conducted at an epilepsy service of a teaching hospital in Australia.
51 patients were randomized to levetiracetam whereas 48 were randomized to a second older AED, either to valproate (n=25) or carbamazepine ( n= 23).
The investigators found that there were no differences between the groups in depression scores at three months. In fact, there was improvement in 17 of the 43 patients (39.5%) of the levetiracetam group, and 15 of 44 patients (34.1%) in the older AED group. But a greater proportion of the older AED group improved on the quality of life in epilepsy inventory compared with the levetiracetam group at 71.1% vs. 48.8%, respectively which was significant. Quality of life, anxiety, and antiepileptic drug (AED adverse effects scores were improved in both groups, three and 12 months after randomization.
Switching to a single agent in a patient experiencing ongoing seizures or having tolerability issues with their first AED is associated with sustained improvement in measures of quality of life, psychiatric and adverse effects outcomes according to this study. Patients switched to levetiracetam do not necessarily have a better outcome than those switched to second older antiepileptic drugs.
The study suggests that switching to an alternative drug may be useful in patients who are not responding appropriately to a given seizure agent. However, switching to levetiracetam may not always lead to improved outcome. Although so much is written about how newer AEDs are better, this paper reminds us that individual responses to drugs still rule the day and some individuals may have improvement with levetiracetam but that adage that one size fits all with a given drug, whether levetiracetam or what ever other choice is made, does not necessarily mean that that all individuals with epilepsy will necessarily have a better outcome when switched to any one drug. Rather, having choices is still important. This analysis informs as to what comparative effectiveness research for individuals with epilepsy should address. It should be less about comparing multiple drugs, and more about finding which drug is most appropriate for a given clinical scenario.
by Joseph I. Sirven, MD
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