We searched the following databases (22 August 2019): the Cochrane Register of Studies (CRS Web), including the Cochrane
Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 August 2019), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP), with no language restrictions. We contacted UCB Pharma (sponsors of
lacosamide).
SELECTION CRITERIA: We used standard Cochrane methodology, assessing the following outcomes: 50% or greater reduction in seizure frequency; seizure freedom; treatment withdrawal; adverse events; quality of life; and cognitive changes. The primary analyses were intention-to-treat. We estimated summary risk ratios (RR) for each outcome presented with 99% confidence intervals (CI), except for 50% or greater seizure reduction, seizure freedom and treatment withdrawal which were presented with 95% CIs. We performed subgroup analyses according to
lacosamide dose and sensitivity analyses according to population age, whereby data from children were excluded from the meta-analysis.
MAIN RESULTS: We included five trials (2199 participants). The risk of bias for all studies was low to unclear. All studies were placebo-controlled and assessed doses from 200 mg to 600 mg per day. One study evaluated
lacosamide in children; all other studies were in adults. Trial duration ranged from 24 to 26 weeks. All studies used adequate methods of randomisation and were double-blind. Overall, the certainty of the evidence for the outcomes was judged as moderate to high, with the exception of seizure freedom which was low. 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). 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). 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). The estimated effect size for most outcomes did not change considerably following sensitivity analysis. For seizure freedom, however, the RR nearly doubled upon the exclusion of data from children (RR 4.04, 95% CI 1.52 to 10.73). Adverse events associated with
lacosamide included: abnormal co-ordination (RR 6.12, 99% CI 1.35 to 27.77), blurred vision (RR 4.65, 99% CI 1.24 to 17.37),
diplopia (RR 5.59, 99% CI 2.27 to 13.79),
dizziness (RR 2.96, 99% CI 2.09 to 4.20),
nausea (RR 2.35, 99% CI 1.37 to 4.02),
somnolence (RR 2.04, 99% CI 1.22 to 3.41),
vomiting (RR 2.94, 99% CI 1.54 to 5.64), and number of participants experiencing one or more adverse events (RR 1.12, 99% CI 1.01 to 1.24). Adverse events that were not significant were:
vertigo (RR 3.71, 99% CI 0.86 to 15.95),
rash (RR 0.58, 99% CI 0.17 to 1.89),
nasopharyngitis (RR 1.41, 99% CI 0.87 to 2.28),
headache (RR 1.34, 99% CI 0.90 to 1.98),
fatigue (RR 2.11, 99% CI 0.92 to 4.85), nystagmus (RR 1.47, 99% CI 0.61 to 3.52), and
upper respiratory tract infection (RR 0.70, 99% CI 0.43 to 1.15).
AUTHORS' CONCLUSIONS: