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Objective  To assess prospectively the effectiveness of lacosamide ( LCM ) added to levetiracetam ( LEV ) after down‐titration of a concomitant sodium channel blocker ( SCB ) among patients with focal epilepsy not adequately controlled on  LEV  and  SCB .    Methods  In this open‐label trial,  LCM  was initiated at 100 mg/day and up‐titrated to 200‐600 mg/day over 9 weeks;  SCB  down‐titration started when  LCM  dose reached 200 mg/day. Patients remained on stable  LCM / LEV  doses for 12 weeks’ maintenance (21‐week treatment period). The primary outcome was retention rate on  LCM .    Results  Due to recruitment challenges, fewer than the planned 300 patients participated in the trial, resulting in the trial being underpowered. Overall, 120 patients (mean age 39.7 years) started and 93 completed the trial. The most frequently used  SCB s were lamotrigine (39.2%), carbamazepine (30.8%) and oxcarbazepine (27.5%). Eighty‐four patients adhered to protocol and discontinued their  SCB  after cross‐titration, but there was insufficient evidence for 36 patients. Retention rate was 73.3% (88/120) for all patients and 83.3% (70/84) for those with evidence of  SCB  discontinuation. Seizure freedom for patients completing maintenance was 14.0% (13/93). Discontinuation due to adverse events (6.7%) and lack of efficacy (3.3%) occurred primarily during cross‐titration. Most frequently reported adverse events during treatment were dizziness (23.3%), headache (15.0%) and fatigue (8.3%).    Conclusions  In patients with uncontrolled seizures on  LEV / SCB , the  LCM / LEV  combination appeared to be effective and well tolerated. A cross‐titration schedule—flexible  LCM  up‐titration, concomitant  SCB  down‐titration and stable background  LEV —could present a feasible and practical approach to initiating  LCM  while minimizing pharmacodynamic interactions with a  SCB .

Lacosamide and sodium channel‐blocking antiepileptic drug cross‐titration against levetiracetam background therapy