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Meta-Analysis
. 2021 May 17;5(5):CD008841.
doi: 10.1002/14651858.CD008841.pub3.

Lacosamide add-on therapy for focal epilepsy

Roshan K Babar  1 , Rebecca Bresnahan  2   3 , Conor S Gillespie  4 , Benedict D Michael  5   6
Affiliations
Meta-Analysis

Lacosamide add-on therapy for focal epilepsy

Roshan K Babar et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an updated version of the Cochrane review published in 2015. Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic drug; many will require add-on therapy. Around a third of people fail to achieve complete seizure freedom despite multiple antiepileptic drugs. Lacosamide has been licenced as an add-on therapy for drug-resistant focal epilepsy.

Objectives: To evaluate the efficacy and tolerability of lacosamide as an add-on therapy for children and adults with drug-resistant focal epilepsy.

Search methods: 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: Randomised controlled trials of add-on lacosamide in people with drug-resistant focal epilepsy.

Data collection and analysis: 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: Lacosamide is effective and well-tolerated in the short term when used as add-on treatment for drug-resistant focal epilepsy. Lacosamide increases the number of people with 50% or greater reduction in seizure frequency and may increase seizure freedom, compared to placebo. Higher doses of lacosamide may be associated with higher rates of adverse events and treatment withdrawal. Additional evidence is required assessing the use of lacosamide in children and on longer-term efficacy and tolerability.

Trial registration: ClinicalTrials.gov NCT01921205.

PubMed Disclaimer

Conflict of interest statement

RKB: none known RB: none known CSG: none known BDM has received funding from the National Institute for Health Research, Medical Research Council, Wellcome Trust, Academy of Medical Sciences, and British Medical Association. No others known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Risk of bias in outcome reporting: Matrix ORBIT Tool displaying the review authors' judgement about risk of bias for each outcome with respect to outcome reporting.
1.1
1.1. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 1: 50% or greater reduction in seizure frequency
1.2
1.2. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 2: Seizure freedom
1.3
1.3. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 3: Treatment withdrawal
1.4
1.4. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 4: Abnormal co‐ordination
1.5
1.5. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 5: Abnormal vision
1.6
1.6. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 6: Accident NOS
1.7
1.7. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 7: Ataxia
1.8
1.8. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 8: Blurred vision
1.9
1.9. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 9: Diplopia
1.10
1.10. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 10: Dizziness
1.11
1.11. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 11: Fatigue
1.12
1.12. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 12: Headache
1.13
1.13. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 13: Nasopharyngitis
1.14
1.14. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 14: Nausea
1.15
1.15. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 15: Nystagmus
1.16
1.16. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 16: Rash
1.17
1.17. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 17: Somnolence
1.18
1.18. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 18: Tremor
1.19
1.19. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 19: Upper respiratory tract infection
1.20
1.20. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 20: Vertigo
1.21
1.21. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 21: Vomiting
1.22
1.22. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 22: One or more adverse events
1.23
1.23. Analysis
Comparison 1: Lacosamide versus placebo, Outcome 23: Serious adverse events
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References

References to studies included in this review

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