Abstracts

Rationale: Psychiatric comorbidities are common in patients with epilepsy. The objective of this post-hoc analysis was to assess the tolerability and effectiveness of lacosamide (LCM) monotherapy for newly diagnosed epilepsy in the specific subgroup of patients with psychiatric comorbidities. Methods: Patients with concomitant psychiatric disorders (MedDRA [Version 16.1] System Organ Class; reported as ongoing at the Screening Visit) enrolled in the double-blind non-inferiority monotherapy trial (SP0993; NCT01243177) assessing the efficacy and tolerability of LCM vs carbamazepine controlled-release (CBZ-CR) were included in this post-hoc analysis. The trial enrolled patients (?-16 years) with newly diagnosed epilepsy (?-2 focal or generalized tonic-clonic seizures [without clear focal origin] in the preceding 12 months [?-1 last 3 months]). LCM (initiated 100mg/day) and CBZ-CR (initiated 200mg/day) were titrated to 200mg/day or 400mg/day, respectively followed by a step-wise dose increase, based on seizure control (400/600mg/day LCM, 800/1200mg/day CBZ-CR). Results: Of the 886 patients that received trial medication, 126 (14.2%; LCM n=64; CBZ-CR n=62) reported ?-1 psychiatric comorbidity as ongoing (at Screening Visit), most frequently depression (38.1%), insomnia (27.8%), and anxiety (26.2%) (Table 1). 50.0% patients on LCM and 35.5% on CBZ-CR completed the study (main reasons for discontinuation [LCM/CBZ-CR]: adverse event [10.9%/24.2%]; lack of efficacy [18.8%/11.3%]). Treatment-emergent adverse events (TEAEs) occurred in 81.3% patients on LCM and 90.3% on CBZ-CR (Table 2). The most frequently reported TEAEs (>10%) on LCM were dizziness, headache and nasopharyngitis and on CBZ-CR dizziness, headache, fatigue, somnolence, GGT increase and nausea. 15 (23.4%) patients on LCM and 10 (16.1%) on CBZ-CR reported psychiatric TEAEs; those reported by ?-3 patients in either group (n [%]; LCM/CBZ-CR) were depression (3 [4.7%]/0] and anxiety (2 [3.1%]/4[6.5%]). No TEAEs of psychotic disorder, epileptic psychosis, or acute psychosis were reported. The proportion of patients completed 6 and 12 months of treatment while remaining seizure free at the last evaluated dose were 67.2% and 50.0% on LCM and 45.2% and 37.1% on CBZ-CR, respectively. Conclusions: This post-hoc analysis suggests that in patients with newly diagnosed epilepsy and psychiatric comorbidities LCM monotherapy was efficacious and generally well tolerated with a discontinuation rate due to TEAEs similar to that of the overall LCM population enrolled in the trial. Funding: UCB Pharma-sponsored.