PMID- 29324401
OWN - NLM
STAT- MEDLINE
DCOM- 20180314
LR  - 20181202
IS  - 1532-2688 (Electronic)
IS  - 1059-1311 (Linking)
VI  - 55
DP  - 2018 Feb
TI  - Unblinded, randomized multicenter trial comparing lamotrigine and valproate 
      combination with controlled-release carbamazepine monotherapy as initial drug 
      regimen in untreated epilepsy.
PG  - 17-24
LID - S1059-1311(17)30697-0 [pii]
LID - 10.1016/j.seizure.2017.12.008 [doi]
AB  - PURPOSE: To compare controlled-release carbamazepine monotherapy (CBZ-CR) with 
      lamotrigine and valproate combination therapy (LTG + VPA) in equivalent total 
      drug load, as initial drug regimen in untreated patients with partial and/or 
      generalized tonic-clonic seizures (GTCS). METHODS: This unblinded, randomized, 
      60-week superiority trial recruited patients having two or more unprovoked 
      seizures with at least one seizure during previous three months. After 
      randomization into CBZ-CR or LTG + VPA, patients entered into eight-week 
      titration phase (TP), followed by 52-week maintenance phase (MP). Median doses of 
      CBZ-CR and LTG + VPA were 600 mg/day and 75 mg/day + 500 mg/day, respectively. 
      Primary outcome measure was completion rate (CR), a proportion of patients who 
      have completed the 60-week study as planned. Secondary efficacy measures included 
      seizure-free rate (SFR) for 52-week of MP and time to first seizure (TTFS) during 
      MP. RESULTS: Among 207 randomized patients, 202 underwent outcome analysis (104 
      in CBZ-CR, 98 in LTG + VPA). CR was 62.5% in CBZ-CR and 65.3% in LTG + VPA 
      (p = 0.678). SFR during MP was higher in LTG + VPA (64.1%) than CBZ-CR (47.8%) 
      (P = 0.034). TTFS was shorter with CBZ-CR (p = 0.041). Incidence of adverse 
      effects (AEs) were 57.7% in CBZ-CR and 60.2% in LTG + VPA and premature drug 
      withdrawal rates due to AEs were 12.5% and 7.1%, respectively, which were not 
      significantly different. CONCLUSION: CR was comparable between LTG + VPA and 
      CBZ-CR, however, both SFR for 52-week MP and TTFS during MP were in favor of 
      LTG + VPA than CBZ-CR. The study suggested that LTG + VPA can be an option as 
      initial drug regimen for untreated patients with partial seizures and/or GTCS 
      except for women of reproductive age.
CI  - Copyright (c) 2017 British Epilepsy Association. Published by Elsevier Ltd. All 
      rights reserved.
FAU - Lee, Byung In
AU  - Lee BI
AD  - Department of Neurology, Yonsei University College of Medicine, Seoul, Korea; 
      Department of Neurology, Inje University College of Medicine, Busan, Korea. 
      Electronic address: bilee@paik.ac.kr.
FAU - No, Soon Kee
AU  - No SK
AD  - Department of Neurology, Bong Seng Memorial Hospital, Busan, Korea.
FAU - Yi, Sang-Doe
AU  - Yi SD
AD  - Department of Neurology, Keimyung University School of Medicine, Daegu, Korea.
FAU - Lee, Hyang Woon
AU  - Lee HW
AD  - Department of Neurology, Ewha Womans University School of Medicine, Seoul, Korea.
FAU - Kim, Ok Joon
AU  - Kim OJ
AD  - Department of Neurology, CHA University, Seongnam, Korea.
FAU - Kim, Sang Ho
AU  - Kim SH
AD  - Department of Neurology, Dong-A University College of Medicine, Busan, Korea.
FAU - Kim, Myeong Kyu
AU  - Kim MK
AD  - Department of Neurology, Chonnam National University Medical School, Gwangju, 
      Korea.
FAU - Kim, Sung Eun
AU  - Kim SE
AD  - Department of Neurology, Inje University College of Medicine, Busan, Korea.
FAU - Kim, Yo Sik
AU  - Kim YS
AD  - Department of Neurology, Wonkwang University School of Medicine, Iksan, Korea.
FAU - Kim, Jae Moon
AU  - Kim JM
AD  - Department of Neurology, Chungnam National University School of Medicine, 
      Daejeon, Korea.
FAU - Lee, Se-Jin
AU  - Lee SJ
AD  - Department of Neurology, Yeungnam University College of Medicine, Daegu, Korea.
FAU - Shin, Dong Jin
AU  - Shin DJ
AD  - Department of Neurology, Gachon University Medical Center, Incheon, Korea.
FAU - Park, Sung Pa
AU  - Park SP
AD  - Department of Neurology, Kyungpook National University School of Medicine, Daegu, 
      Korea.
FAU - Kim, Yeong In
AU  - Kim YI
AD  - Department of Neurology, The Catholic University of Korea College of Medicine, 
      Seoul, Korea.
FAU - Heo, Kyoung
AU  - Heo K
AD  - Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
FAU - Cho, Yong Won
AU  - Cho YW
AD  - Department of Neurology, Keimyung University School of Medicine, Daegu, Korea.
FAU - Cho, Yang-Je
AU  - Cho YJ
AD  - Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
FAU - Kim, Youn Nam
AU  - Kim YN
AD  - Clinical Trial Center, Yonsei University Health System, Severance Hospital, 
      Seoul, Korea.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20171229
PL  - England
TA  - Seizure
JT  - Seizure
JID - 9306979
RN  - 0 (Anticonvulsants)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Triazines)
RN  - 33CM23913M (Carbamazepine)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - U3H27498KS (Lamotrigine)
SB  - IM
MH  - Adult
MH  - Anticonvulsants/administration & dosage/*therapeutic use
MH  - Carbamazepine/administration & dosage/*therapeutic use
MH  - Delayed-Action Preparations
MH  - Drug Therapy, Combination
MH  - Epilepsy/*drug therapy
MH  - Female
MH  - Humans
MH  - Lamotrigine
MH  - Male
MH  - Triazines/administration & dosage/*therapeutic use
MH  - Valproic Acid/administration & dosage/*therapeutic use
OTO - NOTNLM
OT  - CBZ-CR
OT  - Combination therapy
OT  - Initial drug regimen
OT  - LTG + VPA
OT  - Monotherapy
EDAT- 2018/01/13 06:00
MHDA- 2018/03/15 06:00
CRDT- 2018/01/12 06:00
PHST- 2017/10/20 00:00 [received]
PHST- 2017/12/26 00:00 [revised]
PHST- 2017/12/28 00:00 [accepted]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2018/03/15 06:00 [medline]
PHST- 2018/01/12 06:00 [entrez]
AID - S1059-1311(17)30697-0 [pii]
AID - 10.1016/j.seizure.2017.12.008 [doi]
PST - ppublish
SO  - Seizure. 2018 Feb;55:17-24. doi: 10.1016/j.seizure.2017.12.008. Epub 2017 Dec 29.