Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Sodium channel blockers

15 evidence topics · 13 sources

First-line monotherapy for focal seizures

“Consider lamotrigine or levetiracetam as first-line monotherapy for people with focal seizures. If the first choice is unsuccessful, consider the other of these options.” (opens the source at this quote in a new tab)

Second-line and third-line monotherapy

“They agreed that if these treatments were unsuccessful, carbamazepine, oxcarbazepine or zonisamide could be considered for second-line monotherapy. The evidence was weaker for lacosamide, so this was included as a third-line option.” (opens the source at this quote in a new tab)
“If second-line monotherapies tried are unsuccessful in people with focal seizures, consider lacosamide as third-line monotherapy.” (opens the source at this quote in a new tab)

Comparative retention and tolerability evidence

“The evidence showed that lamotrigine and levetiracetam were continued for longer than other drugs for treating focal epilepsy, suggesting that they may be more effective and better tolerated. However, the evidence also suggested they were not more effective than other drugs in terms of remission at 6 and 12 months, and the evidence for time to first seizure suggested they were less effective than carbamazepine.” (opens the source at this quote in a new tab)

Initial monotherapy in new-onset adult focal epilepsy

“Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy.” (opens the source at this quote in a new tab)
“LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years with new-onset focal epilepsy.” (opens the source at this quote in a new tab)

Adjunctive sodium channel blockers in treatment-resistant focal epilepsy

“Lacosamide, eslicarbazepine, and extended-release topiramate use should also be considered to decrease seizure frequency in this population (Level B).” (opens the source at this quote in a new tab)
“Eslicarbazepine use may be considered to decrease seizure frequency as monotherapy for TRAFE (Level C).” (opens the source at this quote in a new tab)

Evidence levels for initial monotherapy for adult focal seizures

“Levetiracetam and zonisamide join carbamazepine and phenytoin with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures.” (opens the source at this quote in a new tab)
“Selection of the initial AED therapy for a person with newly diagnosed or untreated seizures requires integration of evidence and expert opinion for the patient-specific, AED-specific, and nation-specific variables that can impact overall response to therapy.” (opens the source at this quote in a new tab)

Lamotrigine compared with levetiracetam and zonisamide in newly diagnosed focal epilepsy

“Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95–1·47)” (opens the source at this quote in a new tab)
“These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy.” (opens the source at this quote in a new tab)
“Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials.” (opens the source at this quote in a new tab)
“Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide.” (opens the source at this quote in a new tab)

Mechanistic basis of the sodium channel blocking class

“Classical ASMs such as phenytoin, carbamazepine, oxcarbazepine (OXC), and lamotrigine preferentially bind to sodium channels in the inactivated state.” (opens the source at this quote in a new tab)
“Enhancement of slow inactivation of sodium channels by newer ASMs, such as lacosamide (LCM) and eslicarbazepine acetate (ESL), represents an innovative mechanism distinguishing them from classical VGSC blockers” (opens the source at this quote in a new tab)

Adjunctive lacosamide: pooled efficacy and withdrawal

“The RR for a 50% or greater reduction in seizure frequency for all doses of lacosamide compared with placebo was 1.79 (95% CI 1.55 to 2.08; 5 studies; 2199 participants; high-certainty evidence).” (opens the source at this quote in a new tab)
“The RR for seizure freedom for all doses of lacosamide compared with placebo was 2.27 (95% CI 1.35 to 3.83; 5 studies; 2199 participants; low-certainty evidence).” (opens the source at this quote in a new tab)
“The RR for treatment withdrawal for all doses of lacosamide compared with placebo was 1.57 (95% CI 1.24 to 1.98; 5 studies; 2199 participants; moderate-certainty evidence).” (opens the source at this quote in a new tab)

Adjunctive lacosamide: pivotal trial

“Median percent reductions in seizure frequency per 28 days from baseline to maintenance (intention-to-treat, ITT) were 37.3% for lacosamide 400 mg/day (p = 0.008) and 37.8% for lacosamide 600 mg/day (p = 0.006) compared to 20.8% for placebo, with responder rates of 38.3% and 41.2%, respectively, compared to placebo (18.3%, p < 0.001; ITT).” (opens the source at this quote in a new tab)

Adjunctive lacosamide: seizure freedom in pooled trials

“A total of 2.7%, 3.3% and 4.8% of patients completing the Maintenance Phase in the lacosamide 200, 400 and 600 mg/day groups, respectively, experienced no seizures throughout the entire Maintenance Phase (placebo group = 0.9%).” (opens the source at this quote in a new tab)

Adjunctive eslicarbazepine acetate: pooled efficacy

“For adults, the RR was 1.71 (95% CI 1.42 to 2.05; 5 studies, 1799 participants; moderate-certainty evidence)” (opens the source at this quote in a new tab)
“ESL was associated with seizure freedom (RR 3.16, 95% CI 1.73 to 5.78; 6 studies, 1922 participants; moderate-certainty evidence).” (opens the source at this quote in a new tab)
“ESL reduces seizure frequency when used as an add-on treatment for adults with drug-resistant focal epilepsy.” (opens the source at this quote in a new tab)

Adjunctive eslicarbazepine acetate: pivotal trial responder rate

“Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%).” (opens the source at this quote in a new tab)
“The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia.” (opens the source at this quote in a new tab)

Adjunctive oxcarbazepine: pooled efficacy

“Oxcarbazepine may increase the responder rate for 50% or greater reduction in seizure frequency compared to control treatment (RR 1.80, 95% CI 1.27 to 2.56; random-effects model; 6 studies; low-certainty evidence).” (opens the source at this quote in a new tab)
“Treatment with oxcarbazepine was associated with an increased treatment withdrawal rate compared to control (RR 1.75, 95% CI 1.44 to 2.13; fixed-effect model; 6 studies; moderate-certainty evidence).” (opens the source at this quote in a new tab)

Adjunctive lamotrigine: pooled efficacy

“The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate-certainty evidence)” (opens the source at this quote in a new tab)
“Lamotrigine as an add-on treatment for drug-resistant focal seizures appears to be effective in reducing seizure frequency, and seems to be fairly well-tolerated.” (opens the source at this quote in a new tab)