Merck
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  • A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy.

A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy.

Epilepsia (2015-02-17)
Konrad J Werhahn, Eugen Trinka, Judith Dobesberger, Iris Unterberger, Petra Baum, Maria Deckert-Schmitz, Tobias Kniess, Bettina Schmitz, Viviane Bernedo, Christian Ruckes, Anne Ehrlich, Günter Krämer
ABSTRACT

To compare the effectiveness of controlled-released carbamazepine (CR-CBZ) to levetiracetam (LEV) and to lamotrigine (LTG) in elderly patients with newly diagnosed focal epilepsy. Randomized, double-blind, parallel-group trial conducted between January 2007 and August 2011, in 47 ambulatory or hospital sites in Germany, Austria, or Switzerland. Eligible participants were aged ≥ 60, had new-onset epilepsy, had no acute illness as the cause of their seizures, and had no contraindication to the drugs in the trial. Patients were randomized 1:1:1 to CR-CBZ, LTG, or LEV. Doses were up-titrated for 6 weeks and could be maintained or adjusted depending on seizure relapse or tolerability over an additional period of 52 weeks. Primary outcome was the retention to treatment at week 58; secondary measures related to seizure and adverse event frequency. Of 361 randomized patients, 359 were included (CR-CBZ n = 121, LTG n = 117, LEV n = 122) in the modified intent-to-treat population (mean age [range] 71.4 [60-95] years). At week 58, the retention rate for LEV was significantly higher than for CR-CBZ (61.5% vs. 45.8%, p = 0.02), and similar to LTG (55.6%). Seizure freedom rates at weeks 30 and 58 were not different across the groups. Twice as many patients receiving CR-CBZ discontinued due to adverse events or death compared to those in the LEV group (32.2% vs. 17.2%; odds ratio 2.28, 95% confidence interval [CI] 1.25-4.19, p = 0.007), whereas discontinuation was intermediate for LTG (26.3%). Median daily doses of completers (n = 195) were CR-CBZ 380.0 mg/day (333.0-384.0), LTG 95 mg/day (94.0-97.0), and LEV 950 mg/day (940.0-985.0). In the initial monotherapy of focal epilepsy in the elderly, 1-year retention to LEV was higher compared to CR-CBZ due to better tolerability. Retention of LTG was intermediate and close to LEV, but did not differ significantly from either comparators. NCT00438451, www.clinicaltrials.gov.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lamotrigine, ≥98%, powder
Supelco
Carbamazepine, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Lamotrigine, United States Pharmacopeia (USP) Reference Standard
Lamotrigine for system suitability, European Pharmacopoeia (EP) Reference Standard
Lamotrigine for peak identification, European Pharmacopoeia (EP) Reference Standard
Lamotrigine, European Pharmacopoeia (EP) Reference Standard
Supelco
Carbamazepine, analytical standard
Carbamazepine, European Pharmacopoeia (EP) Reference Standard
Supelco
Lamotrigine, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Carbamazepine, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Carbamazepine, meets USP testing specifications
Levetiracetam, European Pharmacopoeia (EP) Reference Standard
USP
Levetiracetam, United States Pharmacopeia (USP) Reference Standard
Supelco
Levetiracetam, Pharmaceutical Secondary Standard; Certified Reference Material