PMID- 31374046
OWN - NLM
STAT- MEDLINE
DCOM- 20190812
LR  - 20221005
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 98
IP  - 31
DP  - 2019 Aug
TI  - A statistical analysis plan for a randomized clinical trial to evaluate the 
      efficacy and safety of ethosuximide in patients with treatment-resistant 
      depression.
PG  - e16674
LID - 10.1097/MD.0000000000016674 [doi]
LID - e16674
AB  - BACKGROUND AND OBJECTIVE: A recent striking advance in the treatment of 
      depression has been the finding of rapid antidepressant effects in over 70% of 
      patients with treatment-resistant depression (TRD) using ketamine. However, the 
      potential risk of addiction may limit its clinical use. Recent research revealed 
      that blockade of N-methyl-D-aspartate receptor (NMDAR) dependent bursting 
      activity in the lateral habenula (LHb) could mediate the fast antidepressant 
      effects of ketamine. Further, LHb bursting plays an important role in the 
      pathophysiology of depression that requires both NMDARs and low-voltage-sensitive 
      T-type calcium channels (T-VSCCs). Ethosuximide, which is used to treat absence 
      seizures, is a T-VSCCs inhibitor, may be a novel drug candidate for depression. 
      The objective of this clinical trial is to investigate the efficacy and safety of 
      ethosuximide in patients with TRD. DESIGN: The study is a single center, 
      randomized, double-blind, placebo-controlled, parallel-group, two-stage clinical 
      trial. Forty patients with TRD will be randomly assigned to Group A (treatment 
      group) or Group B (control group). In the first stage ethosuximide or placebo 
      will be given for 2 weeks. In the second stage, escitalopram (or another 
      antidepressant if escitalopram has been used before) will be given for the next 4 
      weeks for all trial patients to ensure effective treatment. The primary outcome 
      measure is the Montgomery-Asberg Depression Rating Scale (MADRS) scores. 
      Secondary outcome measures include the Quick Inventory of Depressive 
      Symptomatology-Self Report score, Hamilton Anxiety Rating Scale scores, 
      individual scores of MADRS, and Young Mania Rating Scale scores. All these scales 
      are measured at baseline and at each treatment visit. Two-way repeated measures 
      analysis of variance is used to analyze the study outcomes. DISCUSSION: A 
      statistical analysis plan is employed to enhance the transparency of the clinical 
      trial and reduce the risks of outcome reporting bias and data-driven results.
FAU - Jiang, Jiajun
AU  - Jiang J
AD  - Department of Psychiatry, the First Affiliated Hospital, College of Medicine, 
      Zhejiang University.
FAU - Wang, Zheng
AU  - Wang Z
AD  - Department of Psychiatry, the First Affiliated Hospital, College of Medicine, 
      Zhejiang University.
AD  - The Key Laboratory of Mental Disorder's Management of Zhejiang Province.
AD  - Brain Research Institute of Zhejiang University.
FAU - Dong, YiYan
AU  - Dong Y
AD  - Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry 
      of Health of China, School of Medicine, Interdisciplinary Institute of 
      Neuroscience and Technology, Qiushi Academy for Advanced Studies.
FAU - Yang, Yan
AU  - Yang Y
AD  - Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry 
      of Health of China, School of Medicine, Interdisciplinary Institute of 
      Neuroscience and Technology, Qiushi Academy for Advanced Studies.
AD  - Mental Health Center, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Ng, Chee H
AU  - Ng CH
AD  - Department of Psychiatry, University of Melbourne, Melbourne, Victoria, 
      Australia.
FAU - Ma, Shuangshuang
AU  - Ma S
AD  - Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry 
      of Health of China, School of Medicine, Interdisciplinary Institute of 
      Neuroscience and Technology, Qiushi Academy for Advanced Studies.
FAU - Xu, Yi
AU  - Xu Y
AD  - Department of Psychiatry, the First Affiliated Hospital, College of Medicine, 
      Zhejiang University.
AD  - The Key Laboratory of Mental Disorder's Management of Zhejiang Province.
AD  - Brain Research Institute of Zhejiang University.
FAU - Hu, Hailan
AU  - Hu H
AD  - Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry 
      of Health of China, School of Medicine, Interdisciplinary Institute of 
      Neuroscience and Technology, Qiushi Academy for Advanced Studies.
AD  - Mental Health Center, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Hu, Shaohua
AU  - Hu S
AD  - Department of Psychiatry, the First Affiliated Hospital, College of Medicine, 
      Zhejiang University.
AD  - The Key Laboratory of Mental Disorder's Management of Zhejiang Province.
AD  - Brain Research Institute of Zhejiang University.
LA  - eng
PT  - Clinical Trial Protocol
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Antidepressive Agents)
RN  - 5SEH9X1D1D (Ethosuximide)
SB  - IM
MH  - Antidepressive Agents/*therapeutic use
MH  - Depressive Disorder, Treatment-Resistant/*drug therapy
MH  - Double-Blind Method
MH  - Ethosuximide/pharmacology/*therapeutic use
MH  - Humans
MH  - Psychiatric Status Rating Scales
MH  - Randomized Controlled Trials as Topic
MH  - Treatment Outcome
PMC - PMC6709087
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2019/08/03 06:00
MHDA- 2019/08/14 06:00
PMCR- 2019/08/02
CRDT- 2019/08/03 06:00
PHST- 2019/08/03 06:00 [entrez]
PHST- 2019/08/03 06:00 [pubmed]
PHST- 2019/08/14 06:00 [medline]
PHST- 2019/08/02 00:00 [pmc-release]
AID - 00005792-201908020-00044 [pii]
AID - MD-D-19-05117 [pii]
AID - 10.1097/MD.0000000000016674 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2019 Aug;98(31):e16674. doi: 10.1097/MD.0000000000016674.