Substitution Monotherapy With Levetiracetam vs Older Antiepileptic Drugs

Abstract

To determine whether patients who fail their first antiepileptic drug (AED) have better neuropsychiatric and quality-of-life (QOL) outcomes if substituted to levetiracetam monotherapy compared with a second older AED. Design: Randomized comparative trial. Participants with partial epilepsy who had failed monotherapy with phenytoin sodium, carbamazepine, or valproate sodium were randomized to substitution monotherapy with levetiracetam or a different older AED. Assessments were performed at baseline, 3 months, and 12 months using questionnaires measuring neuropsychiatric, QOL, seizure control, AED adverse effects, and neurocognitive outcomes. Setting: Epilepsy service of a teaching hospital. Patients: Fifty-one patients were randomized to levetiracetam and 48 were randomized to a second older AED (25 to valproate and 23 to carbamazepine). Main Outcome Measures: Proportions showing improvements in depression (on the Hospital Anxiety and Depression Scale) and QOL scores (on the 89-item Quality of Life in Epilepsy Inventory) at 3 months. Results: There were no differences between the groups in depression scores at 3 months (improvement in 17 of 43 patients [39.5%] in the levetiracetam group and 15 of 44 patients [34.1%] in the older AED group; P=.60), but a greater proportion of the older AED group improved on the 89-item Quality of Life in Epilepsy Inventory compared with the levetiracetam group (27 of 38 patients [71.1%] vs 21 of 43 patients [48.8%], respectively; P =.04). The QOL, anxiety, and AED adverse effects scores were improved in both groups at 3 and 12 months after randomization. Conclusions: Substitution monotherapy in a patient experiencing ongoing seizures or tolerability issues is associated with sustained improvements in measures of QOL, psychiatric, and adverse events outcomes. Patients switched to levetiracetam do not have better outcomes than those switched to a second older AED.

Monotherapy with Levetiracetam Versus Older AEDs: A Randomized Comparative Trial of Effects on Bone Health

“…The sample size calculation was based upon the depression scores primary endpoint of the KONQUEST study, as described in Hakami et al 2012 [20]. The study was not specifically powered for bone health measures, which were secondary endpoints.…”

“…This was a pragmatic, single-centre, prospective, open-label study with blinded endpoint ascertainment. Eligible patients were recruited from the KONQUEST study (Keppra versus Older AEDs evaluating Neuropsychiatric, Neurocognitive and QUality of life outcomes in treatment of Epilepsy as Substitution monoTherapy) [20].…”

“…If the initial AED treatment had been carbamazepine or phenytoin the patient was randomized to levetiracetam or valproate, and if the initial AED treatment was valproate the patient was randomized to levetiracetam or carbamazepine. Details of randomization are described in Hakami et al [20]. The primary endpoints of the KONQUEST study were the proportions of patients who showed improvement in depression symptoms and quality of life at three months following randomization [20].…”

“…Details of randomization are described in Hakami et al [20]. The primary endpoints of the KONQUEST study were the proportions of patients who showed improvement in depression symptoms and quality of life at three months following randomization [20]. Hence a balanced randomization schedule, based upon baseline Hospital Anxiety and Depression Scale (HADS) [21] depression score permuted blocks, was used to ensure that the two treatment groups were equivalent with regards to the numbers of patients reporting depressive symptomatology (HADS depression score >7) at baseline.…”

“…Hence a balanced randomization schedule, based upon baseline Hospital Anxiety and Depression Scale (HADS) [21] depression score permuted blocks, was used to ensure that the two treatment groups were equivalent with regards to the numbers of patients reporting depressive symptomatology (HADS depression score >7) at baseline. Permuted blocks ensured a balance after every 4th treatment allocation, within each level of baseline scores (Figure 1 in Hakami et al 2012 [20]. The bone health measures were not considered in the randomization, which was conducted by a research scientist who had no contact with study patients.…”