PMID- 29604484
OWN - NLM
STAT- MEDLINE
DCOM- 20190221
LR  - 20190221
IS  - 1525-5069 (Electronic)
IS  - 1525-5050 (Linking)
VI  - 82
DP  - 2018 May
TI  - Psychiatric and cognitive adverse events: A pooled analysis of three phase III 
      trials of adjunctive eslicarbazepine acetate for partial-onset seizures.
PG  - 119-127
LID - S1525-5050(17)30333-5 [pii]
LID - 10.1016/j.yebeh.2017.12.017 [doi]
AB  - OBJECTIVE: To evaluate the nature and incidence of psychiatric and cognitive 
      adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as 
      adjunctive treatment for refractory partial-onset seizures (POS) in adults. 
      METHODS: This was a post-hoc analysis of data pooled from three randomized 
      double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 
      8-week baseline period, patients received placebo or adjunctive ESL 400mg 
      (studies 301 and 302 only), 800mg, or 1200mg once daily (QD) for 14weeks (2-week 
      titration period, 12-week maintenance period). Psychiatric and cognitive AEs were 
      identified from individual patient data. Suicidality was also evaluated using the 
      Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or the 
      Columbia-Suicide Severity Rating Scale (C-SSRS). P-values were obtained using the 
      chi-square test of independence or Fisher's exact test, without correcting for 
      multiplicity. RESULTS: The analysis population included 1447 patients (ESL, 
      n=1021; placebo, n = 426). Psychiatric treatment-emergent AEs (TEAEs) occurred in 
      10.8% of patients receiving ESL, and in a comparable proportion (10.3%) of 
      patients receiving placebo (p=0.802). The incidence of depression and 
      suicidality-related TEAEs was higher for ESL (7.4%) vs. placebo (3.8%) (p=0.009). 
      The occurrence of these TEAEs differed between treatment groups (p = 0.010), but 
      there was no notable trend between increasing ESL dose and increasing incidence 
      of depression and suicidality-related TEAEs. Aggression/hostility-related TEAEs 
      occurred in <0.1% of patients taking ESL vs. 0.9% taking placebo. The incidence 
      of cognitive TEAEs was higher for ESL (7.1%) vs. placebo (4.0%) (p=0.023); 
      incidences of memory impairment, attention disturbance, apathy, and aphasia were 
      higher for ESL 1200mg than for other treatment groups. Incidences of psychiatric 
      and cognitive serious AEs (SAEs) were 0.6% and 0.2% with ESL, and 0.5% and 0% 
      with placebo, respectively. Psychiatric and cognitive TEAEs leading to 
      discontinuation occurred in 1.9% and 1.4% of patients taking ESL, and 0.7% and 
      0.5% taking placebo, respectively. CONCLUSIONS: In phase III clinical trials of 
      adjunctive ESL for treatment-refractory POS, psychiatric and cognitive TEAEs were 
      reported infrequently with ESL and placebo. The incidences of depression and 
      suicidality-related TEAEs and of cognitive TEAEs were higher for patients taking 
      ESL vs. placebo. Incidences of psychiatric and cognitive SAEs, and TEAEs leading 
      to discontinuation, were low with ESL and placebo.
CI  - Copyright (c) 2017. Published by Elsevier Inc.
FAU - Andermann, Eva
AU  - Andermann E
AD  - Neurogenetics Unit and Epilepsy Research Group, Montreal Neurological Institute 
      and Hospital, 3801 University Street, Suite 127, Montreal, QC H3A 2B4, Canada; 
      Department of Neurology and Neurosurgery, Department of Human Genetics, McGill 
      University, Montreal, QC, Canada. Electronic address: eva.andermann@mcgill.ca.
FAU - Biton, Victor
AU  - Biton V
AD  - Arkansas Epilepsy Program, Clinical Trials Inc., 2 Lile Court, Suite 100, Little 
      Rock, AR 72205, USA. Electronic address: Vbiton@clinicaltrialsinc.com.
FAU - Benbadis, Selim R
AU  - Benbadis SR
AD  - Department of Neurology, University of South Florida, 2 Tampa General Circle, 7th 
      Floor, Tampa, FL 33606, USA.
FAU - Shneker, Bassel
AU  - Shneker B
AD  - Nuvasive Inc., 7475 Lusk Blvd., San Diego, CA 92121, USA; OhioHealth, 1010 
      Refugee Rd, Pickerington, OH 43147, USA; Ohio State University Wexner Medical 
      Center, 410 W 10th Ave, Columbus, OH 43210, USA(2).
FAU - Shah, Aashit K
AU  - Shah AK
AD  - Wayne State University, 4201 St Antoine, Detroit, MI 48201, USA; Detroit Medical 
      Center, 4201 St. Antoine, Detroit, MI 48201, USA.
FAU - Carreno, Mar
AU  - Carreno M
AD  - Epilepsy Unit, Hospital Clinic, Villarroel 170, Barcelona 08036, Spain.
FAU - Trinka, Eugen
AU  - Trinka E
AD  - Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, 
      Ignaz Harrestrasse 79, Salzburg 5020, Austria; Department of Public Health and 
      Health Technology Assessment, UMIT - University of Health Sciences, Medical 
      Informatics and Technology, 6060 Hall in Tirol, Austria.
FAU - Ben-Menachem, Elinor
AU  - Ben-Menachem E
AD  - Department of Clinical Neuroscience, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg 41345, Sweden.
FAU - Biraben, Arnaud
AU  - Biraben A
AD  - CHU Pontchaillou, 2 Rue Henri le Guilloux, Rennes 35000, France.
FAU - Rocha, Francisco
AU  - Rocha F
AD  - BIAL - Portela & C(a), S.A., Avenida da Siderurgia Nacional, 4745-457 Sao Mamede 
      do Coronado, Portugal.
FAU - Gama, Helena
AU  - Gama H
AD  - BIAL - Portela & C(a), S.A., Avenida da Siderurgia Nacional, 4745-457 Sao Mamede 
      do Coronado, Portugal.
FAU - Cheng, Hailong
AU  - Cheng H
AD  - Sunovion Pharmaceuticals Inc., 84 Waterford Dr, Marlborough, MA 01752, USA.
FAU - Blum, David
AU  - Blum D
AD  - Sunovion Pharmaceuticals Inc., 84 Waterford Dr, Marlborough, MA 01752, USA.
CN  - Study 301, 302 and 304 Investigators
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20180328
PL  - United States
TA  - Epilepsy Behav
JT  - Epilepsy & behavior : E&B
JID - 100892858
RN  - 0 (Anticonvulsants)
RN  - 0 (Dibenzazepines)
RN  - BEA68ZVB2K (eslicarbazepine acetate)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anticonvulsants/*adverse effects
MH  - Clinical Trials, Phase III as Topic/*methods
MH  - Cognitive Dysfunction/*chemically induced/diagnosis/epidemiology
MH  - Depression/chemically induced/epidemiology/psychology
MH  - Depressive Disorder/drug therapy
MH  - Dibenzazepines/*adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Randomized Controlled Trials as Topic/*methods
MH  - Seizures/*drug therapy/epidemiology/psychology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Adverse events
OT  - Cognitive
OT  - Epilepsy
OT  - Eslicarbazepine acetate
OT  - Partial seizures
OT  - Psychiatric
EDAT- 2018/04/01 06:00
MHDA- 2019/02/23 06:00
CRDT- 2018/04/01 06:00
PHST- 2017/04/26 00:00 [received]
PHST- 2017/11/20 00:00 [revised]
PHST- 2017/12/18 00:00 [accepted]
PHST- 2018/04/01 06:00 [pubmed]
PHST- 2019/02/23 06:00 [medline]
PHST- 2018/04/01 06:00 [entrez]
AID - S1525-5050(17)30333-5 [pii]
AID - 10.1016/j.yebeh.2017.12.017 [doi]
PST - ppublish
SO  - Epilepsy Behav. 2018 May;82:119-127. doi: 10.1016/j.yebeh.2017.12.017. Epub 2018 
      Mar 28.