FULL-LENGTH ORIGINAL RESEARCH
The adverse event profile of lacosamide: A systematic review and meta-analysis of randomized controlled trials
Version of Record online: 10 JUL 2012
Wiley Periodicals, Inc. © 2012 International League Against Epilepsy
Volume 54, Issue 1, pages 66–74, January 2013
How to Cite
Zaccara, G., Perucca, P., Loiacono, G., Giovannelli, F. and Verrotti, A. (2013), The adverse event profile of lacosamide: A systematic review and meta-analysis of randomized controlled trials. Epilepsia, 54: 66–74. doi: 10.1111/j.1528-1167.2012.03589.x
- Issue online: 3 JAN 2013
- Version of Record online: 10 JUL 2012
- Accepted May 24, 2012; Early View publication July 10, 2012.
- Antiepileptic drugs;
- Adverse effects;
- Side effects;
Purpose: Defining the tolerability and safety profile of recently marketed antiepileptic drugs, such as lacosamide (LCM), is a prerequisite for their optimal utilization in clinical practice. We aimed to identify any adverse event (AE) associated with LCM treatment by conducting a systematic review and meta-analysis of all available randomized controlled trials (RCTs). We also evaluated the association of serious AEs with LCM, the proportion of study withdrawals due to intolerable AEs at different LCM doses, and whether the tolerability profile of LCM differs according to the disorder in which it was investigated.
Methods: We searched MEDLINE and Cochrane CENTRAL to May 2011 for LCM RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo-controlled, double-blind RCTs and investigated the therapeutic effects of oral LCM in adults with any condition. AEs were assessed for their association with LCM after identification/exclusion of synonyms, rare AEs, and non-assessable AEs. We used risk differences to evaluate the association of any (99% confidence intervals [CIs]) or serious AEs (95% CIs) with LCM and to investigate dose–response relationships of identified AEs.
Key Findings: Ten RCTs (three in pharmacoresistant epilepsy, four in neuropathic pain, one in migraine, one in fibromyalgia, and one in knee osteoarthritis) were included in our study. Their duration varied from 12–18 weeks. The total number of patients included was 3,148. No serious AE was significantly associated with LCM treatment. Of 21 identified AEs, 11 (52%) were found to be significantly associated with LCM. The number of AEs significantly associated with LCM increased with increasing dose: one at 200 mg/day (dizziness); six at 400 mg/day (dizziness, vertigo, abnormal coordination, abnormal vision, nausea, and vomiting); nine at 600 mg/day (dizziness, vertigo, ataxia, balance disorder, diplopia, fatigue, nausea, vomiting, and tremor). The proportion of AE-related study withdrawals also significantly increased with increasing dose. LCM AEs tended to occur more frequently in patients with drug-resistant epilepsy compared with patients with other disorders.
Significance: A range of AEs suggestive of vestibulocerebellar dysfunction is significantly associated with LCM treatment and their incidence increases with increasing doses.