Agomelatine Augmentation Added to SSRIs or SNRIs for Depression

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy and safety of agomelatine augmentation antidepressant therapy in patients with major depressive disorder with inadequate response during early stage of treatment.

Official Title
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Agomelatine Added to SSRIs or SNRIs for Early-nonresponsive Patients With Major Depressive Disorder: a Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

Conditions
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MDD

Intervention / Treatment
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* Drug: Agomelatine
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -1.Aged 18-60 years old; 2.Meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria for a current major depressive episode; 3.Inadequate response to antidepressants with at least 2-weeks treatment duration and under a standard dose. Inadequate response is defined by a < 20% in the percentage change of HAMD-17 score or according to patients' self-report in antidepressant treatment questionnaire. Standard dose is defined as follows: sertraline: >50mg; fluoxetine: >20 mg; citalopram: >20 mg; escitalopram: >10mg; venlafaxine: >150 mg; duloxetine: >60 mg; 4.Score of Clinical Global Impression-Severity (CGI-S) ≥4; 5.Educational level of junior high school and above, having the ability to give informed consent and complete cognitive tests. 6.The primary providers agreeing and patients willing to maintain current antidepressants with the adjunctive treatment of agomelatine. Exclusion Criteria: 1.Current or history of a systematic medical condition (especially rheumatic-immune systemic diseases, endocrine and metabolism diseases, and neurologic system diseases), brain injury or loss of consciousness for more than 5 minutes; 2.Significant current suicidal ideation or suicidal attempt; 3.Meeting the criteria of substance use disorder according to DSM-5 during the past 6 months; 4.History of adjunctive treatment with antidepressants and/or antipsychotics (allowing a combination of small doses of benzodiazepines); 5.Having used anticoagulants (heparin, warfarin, etc.), glucocorticoids or medications for thyroid diseases in the past 3 months; 6.Abnormal urine toxicology or thyroid screening results; 7.History of seizures or family history of epilepsy; 8.History of antidepressant treatment other than medication within the past six months (i.e. ECT, rTMS, psychotherapy); 9.Pregnant or breast breeding women; 10.Color-blindness 11.Transaminase (ALT and AST) showed in liver function tests 2 times above the upper limit of the normal range; 12.Electrocardiogram examination of QTc ≥ 430 ms in male, QTc ≥ 450 ms in female.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experience group<br>In this group,participants take agomelatine at a dose of 25-50 mg/d for 8 weeks. | Drug: Agomelatine<br>* Oral tablets of agomelatine at a dose of 25-50 mg/d for 8 weeks<br>|
| Placebo Comparator: Contral group<br>In this group,participants take a placebo at a dose of 25-50 mg/d for 8 weeks. | Drug: Placebos<br>* Oral tablets of placebos at a dose of 25-50 mg/d for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | The ratio of patients who achieved percentage improvement of HAMD17 score ≥50% | at baseline and in 2, 4 and 8 week | 
| Remission rate | The ratio of patients who achieved HAMD17 score ≤ 7 points | at baseline and in 2, 4 and 8 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adjunctive agomelatine, antidepressant therapy, major depressive disorder