Vanessa Delgado Nunes,1 Laura Sawyer,2 Julie Neilson,1 Grammati Sarri,1 J Helen Cross3,4 1National Clinical Guideline Centre, Royal College of Physicians, London, UK; 2Symmetron Limited, Elstree, UK; 3UCL Institute of Child Health, Great Ormond Street Hospital for Children, London, UK; 4Young Epilepsy, Lingfield, UK Aim: The goal of antiepileptic treatment is to achieve seizure freedom or seizure control. The aim of this paper is to review the evidence for the use of lacosamide for adjunctive treatment of refractory focal seizures with or without secondary generalization, within the scope of the 2012 update of the Clinical Guideline published by the National Institute for Health and Clinical Excellence (NICE). Methods: Clinical evidence for the use of lacosamide and other antiepileptic drugs (AEDs) was systematically reviewed, evaluated, and presented to the Guideline Development Group. Only randomized clinical trials were included. Outcomes of clinical efficacy (seizure freedom, 50% reduction in seizure frequency, time to first seizure, time to 12-month remission, treatment withdrawal, and time to treatment withdrawal), experience of adverse events, and cognitive and quality of life outcomes were reviewed. A decision model was built to weigh the clinical benefits of each adjunctive AED, measured by seizure control and seizure reduction, compared with the harm from adverse events, as measured by withdrawals from treatment due to adverse events. Results: Lacosamide was included as part of the recommended AEDS to be used in tertiary epilepsy centers. The evidence review showed that more participants who received lacosamide as an adjunctive treatment had at least a 50% reduction in seizure frequency compared with those taking placebo. However, more participants on lacosamide were found to experience adverse events and withdrawal from treatment compared with those on placebo. The cost-effectiveness analysis showed that compared with placebo, the benefits gained from adjunctive lacosamide were modest and uncertain, whereas the costs were significantly high. Compared with other AEDs licensed for adjunctive therapy in focal seizures, lacosamide was associated with fewer quality-adjusted life years and higher costs. Therefore, the Guideline Development Group noted that the balance of benefit and harm needs to be carefully monitored in all patients. Keywords: focal seizures, anti-epileptic drug, adjunctive therapy, clinical guideline
