Seizure Control, Tolerability, and Direct Drug Cost of Lamotrigine Versus Carbamazepine in Adults With Focal Epilepsy in a Randomized Open-Label Trial in Bangladesh

Background: Carbamazepine and lamotrigine are both widely used as initial monotherapy for focal epilepsy, but they differ in tolerability and price.In Bangladesh, where most patients pay for medicines themselves, that difference often determines which drug is actually taken.To our knowledge, no randomized comparison of the two drugs has been reported in this population.This trial aimed to compare seizure freedom at six months between lamotrigine and carbamazepine in adults with focal epilepsy and, as secondary objectives, time to first seizure recurrence, serious clinical events, adverse events, adherence, and direct drug cost.Methods: We conducted a prospective, randomized, open-label, parallel-group trial at the Department of Neurology, Dhaka Medical College Hospital, between November 2022 and October 2023.A total of 100 adults with focal epilepsy were allocated in a 1:1 ratio by lottery in blocks of six, with 50 assigned to lamotrigine and 50 to carbamazepine, and followed for six months.The primary outcome was seizure freedom between the month 3 and month 6 visits.Secondary outcomes were seizure freedom at months 1 and 3, time to first seizure recurrence, status epilepticus, hospital admission, death, adverse events, adherence on the four-item Morisky scale, and direct drug cost.Seizure freedom was analyzed in the intention-to-treat population (n = 100), counting missing outcomes as failures, and in the per-protocol population (n = 95), using risk differences with 95% confidence intervals (CIs) and the prespecified noninferiority margin of 30% points.Results: The groups were similar at baseline.Seizure freedom at month 6 was 33 of 50 (66.0%)with lamotrigine and 35 of 50 (70.0%)with carbamazepine in the intention-to-treat analysis (risk difference, -4.0% points; 95% CI, -21.6 to 14.0) and 33 of 48 (68.8%) versus 35 of 47 (74.5%) in the per-protocol analysis (risk difference, -5.7% points; 95% CI, -23.2 to 12.3).Continuous freedom from recurrence through six months was 50.0%versus 55.3% (log-rank p = 0.597).At least one adverse event was reported by 17 (35.4%)participants receiving lamotrigine and 33 (70.2%) receiving carbamazepine (p < 0.001), mainly sedation and fatigue.Two deaths occurred, both in the carbamazepine group.Adherence was similar.The median direct drug cost over six months was 6480 Taka with lamotrigine and 3510 Taka with carbamazepine (p < 0.001).Conclusions: Over six months, seizure freedom did not differ significantly between lamotrigine and carbamazepine, but the CIs were wide, and equivalence or noninferiority against a conventional margin cannot be claimed.Fewer adverse events were reported with lamotrigine, whereas the direct drug cost of carbamazepine was about half that of lamotrigine.Drug choice should be individualized, and larger multicenter trials with longer follow-up are needed.