Title: Efficacy and tolerability of Seizar (lamotrigine) in the treatment of epilepsy (experience of Svt. Luka’s Institute of Child Neurology and Epilepsy)
Abstract: Background. We have accumulated extensive experience in the use of lamotrigine in patients with epilepsy; its mechanism of action, effectiveness, safety, and tolerability are well known. The results of numerous studies indicate its high efficacy and potentially better tolerability compared to other drugs in the treatment of a wide range of epilepsy forms and epileptic syndromes (focal and generalized seizures). These characteristics of lamotrigine determined its priority administration as initial or alternative monotherapy in women with epilepsy. Objective: to review efficacy and tolerability of Seizar in patients with various forms of epilepsy based on long-term experience of using this drug in our center. Materials and methods. We analyzed therapeutic effects of Seizar in 22 patients aged between 3 and 34 years (mean age 15.3 years) treated in Svt. Luka’s Institute of Child Neurology and Epilepsy. The sample included 8 adults and 14 children (under 18 years of age), including 6 children aged from 3 to 12 years. Ten patients were male and twelve patients were female. Study participants were diagnosed with the following forms of epilepsy: idiopathic (genetic) generalized epilepsy (n = 9), idiopathic (genetic) focal epilepsy (n = 2), focal epilepsy of unknown etiology (n = 1), structural and probably structural focal epilepsy (n = 4), genetic and probably genetic epileptic encephalopathies (n = 6). Seizar was used as monotherapy in 9 patients and as an additional drug in 13 patients. Children aged 3 to 12 years received Seizar only as an additional drug in polytherapy (n = 6); patients aged between 12 and 18 years received it either as monotherapy (n = 4) or in addition to other treatments (n = 4). Five adults received Seizar alone, whereas 3 adults received it as a part of polytherapy. In total, 9 participants received monotherapy with Seizar and 13 participants received Seizar with other treatments. In two patients, combination therapy was successfully changed to monotherapy with Seizar (they are currently receiving it as monotherapy). Seizar dose varied between 75 and 400 mg per day given in 1–2 portions. Importantly, prolonged action of Seizar and convenient dose of 200 mg per tablet allows its administration once a day. Currently, 4 patients (one 15-year-old girl and 3 adults) are receiving Seizar once a day (3 of them at bedtime and one of them in the morning). The follow-up period was between 4 months and 5 years. Results. Therapeutic remission with Seizar was achieved in 7 out of 22 patients (31.8 %); 10 patients (45.5 %) demonstrated at least 50 % reduction in seizure frequency; 5 patients (22,7 %) had no effect. None of the participants had seizure aggravation. Seizar was ceased in 2 patients (9 %) due to its inefficacy. Therefore, therapeutic effect (clinical remission or more than 50 % reduction in seizure frequency) was achieved in 17 out of 22 patients (77 %), which is a very good result considering the fact that all participants had severe forms of epilepsy. Seizar was most effective in patients with idiopathic epilepsy (≥50 % reduction in seizure frequency/clinical remission was observed in 9 out 11 patients (81 %), including 5 patients receiving Seizar as monotherapy) and structural focal epilepsy or focal epilepsy of unknown etiology (≥50 % reduction in seizure frequency/clinical remission was observed in 4 out of 5 patients (80 %)). Positive effect was achieved in 4 out of 6 participants (66 %) with epileptic encephalopathies; this group included patients with extremely severe forms of epilepsy and resistance to many antiepileptic drugs (AED). Seizar was well tolerated by patients: 72.8 % of them had no side effect and only 5 patients (22.7 %) had transient disorders of the central nervous system and gastrointestinal tract (nausea, loss of appetite) that did not require discontinuation of the drug. Only one patient (4.5 %) required its cessation. In 4 female patients of reproductive age, Seizar was used to optimize therapy as a part of preparation for pregnancy. High efficacy and good tolerability of Seizar are confirmed by patients’ adherence to treatment: 19 of 22 patients included into the study (86 %) still continue to receive Seizar (the duration of follow-up period varies between 4 months and 5 years). Only 3 participants required drug discontinuation due to skin rash (n = 1; 4.5 %) and low efficacy (n = 2; 9 %). Conclusions. Over the past decades, clinicians have accumulated evidence of good safety and tolerability of lamotrigine, including such aspects as its positive effect on cognitive functions, behavior, mood (including that in children), and particularly good safety profile in women of reproductive age. Lamotrigine and levetiracetam are currently considered the safest AED for women of reproductive age in terms of their impact on the neuroendocrine system of women, fertility, and potential teratogenic effect. The number of pregnancies among women receiving lamotrigine is significantly higher than that among women receiving other AED. Thus, the safety of lamotrigine during pregnancy (as well as other aspects of its safety and tolerability) are studied much better compared to other AED. It is very important that lamotrigine is considered a safe drug.