Abstracts

Rationale: Lacosamide (LCM), (R)-2-acetamido-N-benzyl-3-methoxypropionamide, is a functionalized amino acid with a novel anticonvulsant activity. LCM was approved as an adjunctive treatment for partial-onset seizures in patients ? 16 years by the European Commission (August 2008) and in patients ? 17 years by the U.S. Food and Drug Administration (October 2008). LCM has a novel mode of action (MOA) that appears to be different from existing AEDs, namely the selective enhancement of slow inactivation of voltage-gated sodium channels. However, clinicians have noted that LCM is less well tolerated when it is added to other conventional sodium channel blocking AEDs (SCNBs) such as phenytoin, carbamazepine, oxcarbazepine, or lamotrigine when compared to non-sodium channel blocking AEDs (non-SCNBs). Methods: In order investigate the differences in tolerability of LCM among patients who are already taking SCNBs, we obtained retention data of LCM retrospectively by reviewing clinic records at the Barrow Neurological Institute. The data included patient s age, gender, seizure type, current AEDs, dosage, main reason for discontinuation, and the duration of therapy. To avoid as much bias as possible, only those patients who added LCM after June 3, 2009 and patients were excluded if LCM was started less than six months prior to this study. The patients were then divided into two groups depend on the presence or absence of SCNBs in their concurrent AEDs. Results: A total of 185 patients were taking LCM since June 3, 2009, and among them, LCM was started 6 months or longer in121 patients as an adjunctive therapy for partial epilepsy. Eighty-eight patients were taking at least one of SCNBs (Group A) and 33 were taking non-SCNBs (Group B). Discontinuation of LCM was seen significantly higher in Group A (27.27%) when compared to Group B (9.09%) in 6 months (p<0.0015). The overall discontinuation rate was 20.66% in 6 months after LCM was added. Dizziness was the leading cause of discontinuation (5.79% of 121 patients), and all occurred in Group A (25% of causes for discontinuation in Group A), and none of Group B patients discontinued LCM due to dizziness side effects. Conclusions: This study supports the notion that LCM is less well tolerated when added to SCNBs compared to non-SCNBs as an adjunctive therapy for partial epilepsy. Even though LCM demonstrates unique MOA of selectively enhancing slow inactivation of voltage-gated sodium channels, there may be some pharmacodynamic interactions with other conventional SCNBs, which may impact tolerability of LCM (especially dizziness). Further large prospective studies are needed to confirm the findings of our study, but at this point, LCM should be increased more cautiously when added to SCNBs.