Lamotrigine (Sazar) in the treatment of epilepsy: seven years of experience in Svt. Luka’s Association of Medical Institutions for the Diagnosis, Treatment, and Rehabilitation of Nervous System Diseases and Epilepsy

Aim. To assess the efficacy and tolerability of lamotrigine (Sazar; LLC “Alkaloid-Rus”, Republic of Macedonia) for various forms of epilepsy, based on long-term experience of Svt. Luka Association of Medical Institutions for the Diagnosis, Treatment, and Rehabilitation of Nervous System Diseases and Epilepsy (Svt. Luka’s Institute of Child Neurology and Epilepsy/Svt. Luka’s Institute of Child and Adult Neurology and Epilepsy).

Materials and methods. A retrospective cohort study was conducted based on the analysis of clinical data from 628 patients (aged 3 to 46 years; 595 children and 33 adults (20 women and 13 men); mean age 10.5 years; 319 males and 309 females) monitored at Svt. Luka Association of Medical Institutions for the Diagnosis, Treatment, and Rehabilitation of Nervous System Diseases and Epilepsy who received Sazar over a 7-year period (from June 2018 to September 2025).

Distribution by epilepsy types: structural and presumably structural focal epilepsy/focal epilepsy of unknown etiology (n = 496); genetic and presumably genetic epilepsies, as well as developmental and epileptic encephalopathies (n = 97); idiopathic generalized epilepsies (n = 35).

Sazar was administered as adjunctive therapy or monotherapy at a dose of 3–5 mg/kg/day, with gradual titration over 4–8 weeks to a target dose of 37.5–500.0 mg/day. Subsequently, the dose of Seizar was adjusted depending on the clinical effect, electroencephalography findings, and blood drug concentrations. Three adult female patients received Sazar as a single daily dose of 200 mg/day (at bedtime in 2 cases, and in the morning in 1 case). In all other cases, patients received Sazar twice daily.

Sazar was administered as monotherapy in 176 patients or as adjunctive treatment to other antiepileptic drugs in 452 patients (combination of Sazar with one antiepileptic drug occurred in 379 patients, and with two antiepileptic drugs in 73 patients). In five patients, valproate was added to Sazar, achieving a therapeutic effect without subsequent discontinuation of Sazar. In two patients with high treatment efficacy, a subsequent successful switch from polytherapy to Sazar monotherapy became possible. Twelve patients previously treated with another lamotrigine generic were switched to Sazar without any worsening of epilepsy course.

The follow-up period ranged from 6 months to more than 7 years. Patients followed up for at least 6 months were included in the analysis.

Results. Therapeutic remission was achieved in 306 out of 628 patients (48.72 %) receiving Sazar. Therapeutic remission with Sazar was achieved in 306 out of 628 patients (48.72 %). An additional 157 out of 628 patients (25 %) showed an at least 50 % reduction in seizure frequency; 165 patients had no therapeutic effect (26.3 %).

In 113 cases (17.9 %), Sazar was discontinued due to insufficient efficacy or loss of the initial robust response (after 6–12 months of treatment). Overall, a therapeutic effect (remission or an at least 50 % reduction in seizure frequency) was achieved in 463 out of 628 patients (73.7 %). Given the predominance of patients with drug-resistant forms of epilepsy in this study, this rate can be considered exceptionally high. Considering that the study population predominantly consisted of patients with drug-resistant forms of epilepsy, this rate can be considered exceptionally high.

Sazar demonstrated the highest efficacy in focal epilepsies (structural, presumably structural, structural-genetic, and that of unidentified etiology), as well as in idiopathic generalized epilepsy syndromes. Efficacy was lower in genetic generalized epilepsies and epileptic encephalopathies.

The majority of the patients (n = 573 (91.3 %)) demonstrated good tolerability of Sazar. Sazar-associated side effects were reported in 55 patients (8.76 %). In most cases, transient disturbances such as dizziness, headache, tremor, and nausea were observed, none of which required discontinuation of the medication. Allergic reactions predominantly manifested as a skin rash, which was reported in 37 out of 628 patients (5.8 %), within the first two months of therapy. Angioedema (Quincke’s edema) was reported in one patient. Discontinuation of Sazar due to poor tolerability was required in only 15 of 628 patients (2.4 %), with allergic reactions being the sole reason for treatment cessation. In the remaining cases, the skin rash was transient, did not require drug discontinuation, and its association with lamotrigine treatment remained unproven.

Two female patients of reproductive age started Sazar to reduce the valproate dose that caused severe menstrual disorders, weight gain, alopecia, and edema. Halving the dose of valproate (up to 750 mg/day) in combination with Sazar significantly improved treatment tolerance. One patient gave birth to a healthy baby when she was receiving monotherapy with Sazar at a dose of 350 mg/day.

Improvements in mood (in adult patients) as well as behavior, development, and learning (in children) during Sazar therapy were observed in 380 of 628 patients (60.5 %). In five cases, improvements in mental status during Sazar therapy enabled the discontinuation of antidepressants in adult patients with previously diagnosed depression. No negative effects of Sazar on memory, attention, mood, or behavior were observed in any of the cases, as reported by patients and parents, and in some instances, by a neuropsychologist.

The high efficacy and favorable tolerability of Sazar are confirmed by treatment adherence data, with 500 of 628 patients (79.6 %) continuing the drug throughout the follow-up period (range: 6 months to 7 years).

These data indicate that, with correct titration and close clinical monitoring, lamotrigine can be considered a well-tolerated drug. This is particularly significant for children with comorbid developmental and behavioral disorders, for whom sedative effects and cognitive slowing are of critical concern.

Conclusion. Our analysis demonstrated the high efficacy and favorable tolerability of Sazar in a large cohort, predominantly consisting of pediatric patients, with various forms of epilepsy.