Early Treatment Failure More Likely With Carbamazepine vs Lamotrigine in Epilepsy
The results of this review are applicable primarily to persons with focal onset seizures, with 88% of included participants experiencing this type of seizure at baseline.
In patients with epilepsy, moderate-quality evidence indicates that treatment failure for any reason related to therapy or adverse events (AEs) occurs significantly earlier with carbamazepine than with lamotrigine, although the results for time to first seizure imply that carbamazepine may be superior to lamotrigine for seizure control. Results of the review were published in the Cochrane Database of Systematic Reviews.
The current analysis was an individual participant data review. The primary outcome was time to treatment failure, and secondary outcomes included time to first seizure postrandomization; time to 6-month, 12-month, and 24-month remission; and incidence of AEs.
Among the 14 trials included in this review, individual participant data were available for 2572 of 3787 eligible patients from 9 of 14 trials — 68% of the potential data. In terms of remission outcomes, a hazard ratio (HR) of <1 indicated an advantage for carbamazepine. For first seizure and treatment failure outcomes, an HR of <1 indicated an advantage for lamotrigine.
Lamotrigine showed an advantage over carbamazepine in time to treatment failure for any reason related to treatment (pooled HR adjusted for seizure type: 0.71; 95% CI, 0.62-0.82; moderate-quality evidence) and time to treatment failure because of AEs (pooled HR adjusted for seizure type: 0.55; 95% CI, 0.45-0.66; moderate-quality evidence); however, there was no difference between the 2 therapies for time to treatment failure because of lack of efficacy (pooled HR for all participants: 1.03; 95% CI, 0.75-1.41; moderate-quality evidence).
However, time to first seizure (pooled HR adjusted for seizure type: 1.26; 95% CI, 1.12-1.41; high-quality evidence) and time to 6-month remission (pooled HR adjusted for seizure type: 0.86; 95% CI, 0.76-0.97; high-quality evidence) demonstrated a significant advantage for carbamazepine over lamotrigine for first seizure and 6-month remission.
No difference was observed between the 2 agents for time to 12-month remission (pooled HR for all participants: 0.91; 95% CI, 0.77-1.07; high-quality evidence) or time to 24-month remission (HR for all participants: 1.00; 95% CI, 0.80-1.25; high-quality evidence). Because only 2 trials followed participants for >1 year, however, evidence was limited.
The results of this review are applicable primarily to persons with focal onset seizures, with 88% of included participants experiencing this type of seizure at baseline. Moreover, seizures in up to 50% of persons who were classified as experiencing generalized onset seizures at baseline may have been misclassified. Rates of AEs were similar between the 2 agents.
The investigators concluded that although the methodologic quality of the included trials was generally good, some evidence suggests that the design choice of masked or open-label treatment may have influenced the treatment failure or withdrawal rates reported in these studies. They recommend that future trials be designed to the highest quality possible, taking into account masking, selection of patient population, classification of seizure type, choice of outcomes and analysis, duration of follow-up, and presentation of results.
Nevitt SJ, Tudur Smith C, Weston J, Marson AG. Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst Rev. 2018;6:CD001031.