PMID- 23623245
OWN - NLM
STAT- MEDLINE
DCOM- 20140224
LR  - 20220318
IS  - 1532-2688 (Electronic)
IS  - 1059-1311 (Linking)
VI  - 22
IP  - 7
DP  - 2013 Sep
TI  - Neurological adverse events of new generation sodium blocker antiepileptic drugs. 
      Meta-analysis of randomized, double-blinded studies with eslicarbazepine acetate, 
      lacosamide and oxcarbazepine.
PG  - 528-36
LID - S1059-1311(13)00097-6 [pii]
LID - 10.1016/j.seizure.2013.03.016 [doi]
AB  - PURPOSE: Analysis of overall tolerability and neurological adverse effects (AEs) 
      of eslicarbazepine acetate (ESL), lacosamide (LCM) and oxcarbazepine (OXC) from 
      double-blind, placebo-controlled trials. Indirect comparisons of patients 
      withdrawing because of AEs, and the incidence of some vestibulocerebellar AEs 
      between these three antiepileptic dugs (AEDs). METHODS: We searched MEDLINE for 
      all randomized, double-blind, placebo-controlled trials investigating therapeutic 
      effects of fixed oral doses of ESL, LCM and OXC in patients with drug resistant 
      epilepsy. Withdrawal rate due to AEs, percentages of patients with serious AEs, 
      and the proportion of patients experiencing any neurological AE, nausea and 
      vomiting were assessed for their association with the experimental drug. Analyses 
      were performed between recommended daily doses of each AED according to the 
      approved summary of product characteristics (SPC). Risk differences were used to 
      evaluate the association of any AE [99% confidence intervals (CIs)] or study 
      withdrawals because of AEs (95% CIs) with the experimental drug. Indirect 
      comparisons between withdrawal rate and AEs dizziness, coordination 
      abnormal/ataxia and diplopia were estimated according to network meta-analysis 
      (Net-MA). RESULTS: Eight randomized, placebo-controlled, double-blind trials (4 
      with ESL, 3 with LCM, and 1 with OXC) were included in our analysis. At high 
      doses (OXC 1200mg, ESL 1200mg and LCM 400mg) there was an increased risk of 
      AE-related study withdrawals compared to placebo for all drugs. Several AEs were 
      associated with the experimental drug. Both number and frequency of AEs were 
      dose-related. At high recommended doses, patients treated with OXC withdrew from 
      the experimental treatment significantly more frequently than patients treated 
      with ESL and LCM. Furthermore, the AEs coordination abnormal/ataxia and diplopia 
      were significantly more frequently observed in patients treated with OXC compared 
      to patients treated with LCM and ESL. CONCLUSIONS: The overall tolerability of 
      AEDs and the incidence of several neurological AEs were clearly dose-dependent. 
      Indirect comparisons between these AEDs, taking into account dose-effect, showed 
      that OXC may be associated with more frequent neurological AEs than LCM and ESL.
CI  - Copyright (c) 2013 British Epilepsy Association. Published by Elsevier Ltd. All 
      rights reserved.
FAU - Zaccara, Gaetano
AU  - Zaccara G
AD  - U.O. Neurologia, Azienda Sanitaria di Firenze, Firenze, Italy. 
      gaetano.zaccara@asf.toscana.it
FAU - Giovannelli, Fabio
AU  - Giovannelli F
FAU - Maratea, Dario
AU  - Maratea D
FAU - Fadda, Valeria
AU  - Fadda V
FAU - Verrotti, Alberto
AU  - Verrotti A
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
DEP - 20130425
PL  - England
TA  - Seizure
JT  - Seizure
JID - 9306979
RN  - 0 (Acetamides)
RN  - 0 (Anticonvulsants)
RN  - 0 (Dibenzazepines)
RN  - 0 (Sodium Channel Blockers)
RN  - 33CM23913M (Carbamazepine)
RN  - 563KS2PQY5 (Lacosamide)
RN  - BEA68ZVB2K (eslicarbazepine acetate)
RN  - VZI5B1W380 (Oxcarbazepine)
SB  - IM
MH  - Acetamides/administration & dosage/*adverse effects/therapeutic use
MH  - Anticonvulsants/administration & dosage/*adverse effects/therapeutic use
MH  - Ataxia/chemically induced/epidemiology
MH  - Carbamazepine/administration & dosage/adverse effects/*analogs & 
      derivatives/therapeutic use
MH  - Dibenzazepines/administration & dosage/*adverse effects/therapeutic use
MH  - Diplopia/chemically induced/epidemiology
MH  - Dizziness/chemically induced/epidemiology
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Humans
MH  - Lacosamide
MH  - Nervous System Diseases/*chemically induced/epidemiology/physiopathology
MH  - Oxcarbazepine
MH  - Randomized Controlled Trials as Topic
MH  - Risk Assessment
MH  - Sodium Channel Blockers/administration & dosage/*adverse effects/therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Adverse events
OT  - Antiepileptic drugs
OT  - Epilepsy
OT  - Eslicarbazepine
OT  - Lacosamide
OT  - Oxcarbazepine
EDAT- 2013/04/30 06:00
MHDA- 2014/02/25 06:00
CRDT- 2013/04/30 06:00
PHST- 2012/12/23 00:00 [received]
PHST- 2013/03/28 00:00 [revised]
PHST- 2013/03/29 00:00 [accepted]
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2014/02/25 06:00 [medline]
AID - S1059-1311(13)00097-6 [pii]
AID - 10.1016/j.seizure.2013.03.016 [doi]
PST - ppublish
SO  - Seizure. 2013 Sep;22(7):528-36. doi: 10.1016/j.seizure.2013.03.016. Epub 2013 Apr 
      25.