Investigate the Clinical Responses of Ethosuximide in Patients With Treatment-Resistant Depression.

NCT03887624 | Completed Early Phase 1

• 1 other identifier: 2019-716
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the efficacy and safety of ethosuximide in the treatment of refractory depressive disorder in adults. Half of participants will receive ethosuximide and escitalopram in combination, while the other half will receive a placebo and escitalopram.

Conditions

Depressive Disorder, Treatment-Resistant

Keywords

Depressive Disorder, Treatment-Resistant; ethosuximide

Outcome Measures

Primary Outcomes (1)

• Montgomery and Asberg Depression Rating Scale(MADRS） score

  The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Usual cutoff points are: 0 to 6 - normal/symptom absent, 7 to 19 - mild depression, 20 to 34 - moderate depression, \>34 - severe depression. Changes of MADRS score at therapeutic visit point compare with baseline.

  baseline and 43 days

Secondary Outcomes (6)

• Quick Inventory of Depressive Symptomatology-Self Report(QIDS-SR） score

  baseline and 43 days

• Hamilton Anxiety Rating Scale(HAMA） score

  baseline and 43 days

• MADRS score

  baseline and 43 days

• Young manic rating scale(YMRS） score

  baseline and 43 days

• Efficiency after 2 and 4 weeks of treatment.

  baseline, week 2 and week 4

Study Arms (2)

Experimental group

EXPERIMENTAL

Ethosuximide(2 weeks) + Escitalopram (4 weeks)

Drug: Ethosuximide; Drug: Escitalopram

Control group

PLACEBO COMPARATOR

Placebo(2 weeks)+Escitalopram(4 weeks)

Drug: Placebo; Drug: Escitalopram

Interventions

Ethosuximide DRUG

2 times/day, take it orally after breakfast/dinner; take 500mg in the morning and 500mg in the evening on day1, 500mg in the morning and 750mg in the evening on day2, 750mg in the morning and 750mg in the evening on day3, 750mg in the morning and 1000mg in the evening on day4, 1000mg in the morning and 1000mg in the evening on day5, maintain this dose until the end of treatment for 2 weeks.

Also known as: Zarontin

Experimental group

Placebo DRUG

2 times/day, take it orally after breakfast/dinner; take 500mg in the morning and 500mg in the evening on day1, 500mg in the morning and 750mg in the evening on day2, 750mg in the morning and 750mg in the evening on day3, 750mg in the morning and 1000mg in the evening on day4, 1000mg in the morning and 1000mg in the evening on day5, maintain this dose until the end of treatment for 2 weeks.

Also known as: Placebo(for Ethosuximide)

Control group

Escitalopram DRUG

1 time/day, 20mg/day, take it orally after breakfast, take it for 4 weeks without interruption.

Also known as: Lexapro

Control group; Experimental group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Inpatient of both sexes are aged from 18 to 65 years;
• Diagnosis of major depressive disorder(single or recurrent episodes) is made according to DSM-V(the fifth Edition of Diagnostic and Statistical Manual of Mental Disorders) criteria;
• Subjects with previous or current depressive episodes did not response to two different antidepressants with recommended doses and adequate duration (maximum treatment dose of at least 6 weeks);
• The subjects who will score more than or equal to 22 points on the MADRS scale at screening and baseline period;
• The subjects who will score more than or equal to 3 points on the first clause of MADRS scale at screening and baseline period;
• Subjects who will sign written informed consent and volunteer to participate in the clinical study.

You may not qualify if:

• Diagnoses of other mental disorders (such as organic mental disorders, schizophrenia, bipolar and related disorders, anxiety disorders, obsessive-compulsive disorders and so on) are made according to DSM-V criteria;
• Depressive episodes, such as depression caused by hypothyroidism, secondary to a systemic disease or an organic mental disorder caused by a neurological disease;
• Subjects with a history of attempted suicide, or currently at high suicide risk, or with suicide behavior/attempt, or scoring more than or equal to 3 points on the 10th clause of MADRS scale;
• Subject whose score of MADRS scale in baseline period will be 25% lower than that in screening period;
• Subjects with a history of severe or poorly controlled cardiovascular, liver, kidney, blood, endocrine, respiratory diseases, etc;
• Subjects with a history of epileptic seizures, except for a single febrile convulsion in children;
• Researchers believe that the results of subjects' physical and laboratory examinations are clinically significant abnormalities in screening or baseline period. The following indicators exceed the following criteria: 1)ALT or AST levels are 1.5 times higher than the upper limit of laboratory normal values. 2)Thyroid Function are 1.1 times higher than the upper or lower limit of normal values. 3) Serum creatinine values are 1.1 times higher than the upper limit of normal values. 4)The levels of blood urea nitrogen are higher than the upper limit of normal values;
• The result of electrocardiogram (ECG) is abnormal in screening or baseline period, such as male subjects with QTc interval (\> 450 ms) and female subjects with QTc interval (\> 470 ms) , and the researchers thought it is not suitable for selection;
• Subjects could not swallow oral medicines or have a history of gastrointestinal surgery or any other diseases that may interfere with drug absorption, distribution, metabolism or excretion;
• Monoamine oxidase inhibitors (MAOIs) are taken by subjects now or within 2 weeks before screening. Subjects who took antipsychotics, antidepressants or mood stabilizers before randomization and these drugs' cleaning phase had less than five half-lives. Subjects who took fluoxetine within 1 month before screening. Subjects who continue to take Chinese medicines with antidepressant effects specified in the instructions after signing informed consent.
• Subjects who received modified electroconvulsive therapy (MECT) , transcranial magnetic stimulation (TMS), vagal nerve stimulation (VNS), or systematic psychotherapy within 3 months before screening;
• Subjects with a history of allergies to two or more foods or drugs;
• Subjects who addicted to alcohol or substances within 6 months before screening;
• Prenatal, lactating, or reproductive women who had positive results of HCG tests before participating in the study; Male and female subjects will not take effective contraceptive measures or plan to be pregnant within 3 months after the study;
• Subjects who participated in clinical research within 30 days before signing the informed consent form for this study;

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (1)

Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Location

Related Publications (6)

• Sackeim HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry. 2001;62 Suppl 16:10-7.

  PMID: 11480879 BACKGROUND

• Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.

  PMID: 10686270 BACKGROUND

• Yang Y, Cui Y, Sang K, Dong Y, Ni Z, Ma S, Hu H. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature. 2018 Feb 14;554(7692):317-322. doi: 10.1038/nature25509.

  PMID: 29446381 BACKGROUND

• Cui Y, Yang Y, Ni Z, Dong Y, Cai G, Foncelle A, Ma S, Sang K, Tang S, Li Y, Shen Y, Berry H, Wu S, Hu H. Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression. Nature. 2018 Feb 14;554(7692):323-327. doi: 10.1038/nature25752.

  PMID: 29446379 BACKGROUND

• Sarkisova KY, Kuznetsova GD, Kulikov MA, van Luijtelaar G. Spike-wave discharges are necessary for the expression of behavioral depression-like symptoms. Epilepsia. 2010 Jan;51(1):146-60. doi: 10.1111/j.1528-1167.2009.02260.x. Epub 2009 Aug 8.

  PMID: 19674046 BACKGROUND

• Cui Y, Hu S, Hu H. Lateral Habenular Burst Firing as a Target of the Rapid Antidepressant Effects of Ketamine. Trends Neurosci. 2019 Mar;42(3):179-191. doi: 10.1016/j.tins.2018.12.002.

  PMID: 30823984 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Ethosuximide; Escitalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Succinimides; Imides; Organic Chemicals; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propylamines; Amines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Yi Xu, Doctor of Medicine

  Department of psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is a double-blind and double-simulation design. In the course of clinical study, all subjects, researchers and evaluators are blind to grouping information. The results of the study are audited by blind state data. The placebos are administered in capsules with no difference in appearance, color, weight or odor from the positive drugs. Both subjects and drugs are coded blindly. In the study, the coding system for research drugs have an emergency blindness detection procedure, so as to quickly identify the drugs in emergency medical condition, without destroying the blind design of clinical research.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor of Medicine

Study Record Dates

• First Submitted: March 2, 2019
• First Posted: March 25, 2019
• Study Start: May 21, 2019
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: June 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)