Abstract
Background
Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic drug; many will require add-on treatment with another drug. Sometimes multiple treatment combinations are tried to achieve maximum seizure control, although around a third of people do not achieve complete seizure control. Lacosamide is an antiepileptic drug that has been licensed as an add-on treatment for partial epilepsy.
Objectives
To evaluate the efficacy and tolerability of lacosamide when used as an add-on treatment for patients with drug-resistant partial epilepsy.
Search methods
We searched the Cochrane Epilepsy Group’s Specialized Register (21 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL , The Cochrane Library Issue 4, April 2015), MEDLINE (Ovid, 1946 to 21 May 2015), Scopus (1823 to 13 November 2014),ClinicalTrials.gov (21 May 2015) and the WHO International Clinical Trials Registry Platform (ICTRP, 21 May 2015). We imposed no language restrictions. We contacted UCB (sponsors of lacosamide) and experts in the field.
Selection criteria
Randomised controlled trials of add-on lacosamide in people with drug-resistant partial epilepsy.
Data collection and analysis
Two review authors independently assessed trials for inclusion and extracted the relevant data. We assessed the following outcomes: (1) 50% or greater reduction in seizure frequency; (2) seizure freedom; (3) treatment withdrawal for any reason; and (4) adverse events. Primary analyses were intention-to-treat. Summary risk ratios were estimated for each outcome.
Main results
We included three trials in our review (1311 participants), which were classified as having low risk of bias. All trials were placebo-controlled and assessed doses ranging from 200 mg to 600 mg per day. Trial duration ranged from 24 to 26 weeks. All trials used adequate methods of randomisation and were double-blind. Overall the quality of the evidence was rated as moderate to high. The overall risk ratio for a 50% or greater reduction in seizure frequency for all doses of lacosamide compared with placebo was 1.70 (95% confidence interval (CI) 1.38 to 2.10); for seizure freedom for all doses of lacosamide compared with placebo was 2.50 (95% CI 0.85 to 7.34); and for treatment withdrawal for all doses of lacosamide compared with placebo was 1.88 (95% CI 1.40 to 2.52). Adverse effects significantly associated with lacosamide were abnormal co-ordination (risk ratio (RR) 6.12, 99% CI 1.35 to 27.77), diplopia (RR 5.29, 99% CI 1.97 to 14.23), dizziness (RR 3.53, 99% CI 2.20 to 5.68), nausea (RR 2.37, 99% CI 1.23 to 4.58) and vomiting (RR 3.49, 99% CI 1.43 to 8.54). Adverse effects that were not statistically significant were headache (RR 1.34, 99% CI 0.83 to 2.18), fatigue (RR 2.11, 99% CI 0.92 to 4.85), nystagmus (RR 1.47, 99% CI 0.61 to 3.52) and somnolence (RR 1.44, 99% CI 0.67 to 3.09).
Authors’ conclusions
This review has shown lacosamide to be effective and fairly well tolerated in the short term when used as add-on treatment for drug-resistant partial epilepsy in adults. Higher doses of lacosamide may be more associated with adverse effects and withdrawal of the drug than lower doses. Additional evidence on children is needed, and longer-term efficacy is unknown.
Plain language summary
The use of lacosamide in partial epilepsy: Does it work and is it harmful?
Background
Lacosamide is an antiepileptic drug that can be added along with others to treat people who have certain types of epileptic seizures. This drug may be beneficial for people who are taking other antiepileptic medication but continue to have seizures. This review looked at how well lacosamide works when added to a patient’s daily medication and also looked at some of the harms or side effects of the drug.
Participants
To be included in this review, all participants had to be adults with a diagnosis of epilepsy, specifically having partial seizures. Patients were required to have been already taking at least two other antiepileptic medications that were not currently working to reduce seizures.
Studies
A search for all relevant studies was carried out in May 2015. We included in this review three trials, which studied a total of 1308 people with epilepsy. All three trials were randomised controlled trials, which means that patients were randomly divided into groups and compared. Across all studies were five different groups; one was a placebo group. Patients in this group took medication that was identical to lacosamide in shape and colour but was actually a sugar pill. The other four groups took lacosamide at four different doses.
Results
Review authors found that lacosamide reduced the frequency of seizures. The added antiepileptic drug was over one and a half times better at reducing seizures than placebo. The higher the dose of lacosamide, the better it was at reducing the number of seizures. Also patients who took lacosamide were more likely to have no seizures at all than those who took the placebo, but they were more likely to withdraw from lacosamide largely because of side effects. Side effects included blurred or double vision, problems with co-ordination and feelings of dizziness and nausea.
Quality of the Evidence
Altogether the three trials were judged to use good methods, and so the evidence in this review was rated as high in quality. More research is needed to look at the long-term effects of lacosamide and to explore how well it works in children with epilepsy.
