A Double-blind, Placebo-controlled Study of Antidepressant Augmentation With Agomelatine

Agomelatine Augmentation in Early-Nonresponsive Patients With Major Depressive Disorder Receiving SSRIs or SNRIs: a Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

The purpose of this study was to investigate the efficacy and safety of antidepressant augmentation with agomelatine in the treatment of patients with depression who did not demonstrate satisfying response to selective serotonin reuptake inhibitor (SSRI) and serotonin-noradrenaline reuptake inhibitor (SNRI) during their early phase of treatment; this study also aims to explore the effects of augmenting antidepressant treatment with agomelatine on various aspects, including sleep quality, quality of life, social functioning, and cognitive function in patients with MDD.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Agomelatine; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410001
      • Mental Health Institute & Faculty of Psychiatry of The Second Xiangya Hospital, Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No

Description

1. Age between 18 and 60 years.
2. Meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for a current major depressive episode.

3. Demonstrating an inadequate response to antidepressant treatment lasting at least 2 weeks, at the minimum effective dose for antidepressants. Inadequate response is defined as a < 20% change in the Hamilton Depression Rating Scale-17 (HAMD-17) score or as per patients' self-report in the antidepressant treatment questionnaire. Minimum effective doses for some commonly used classes of antidepressants include:

   • Sertraline: >50mg
   • Fluoxetine: >20 mg
   • Citalopram: >20 mg
   • Escitalopram: >10mg
   • Venlafaxine: >75 mg
   • Duloxetine: >50 mg
4. HAMD-17≥17; Clinical Global Impression-Severity (CGI-S) score ≥4.
5. Education level of at least 6 years, with the ability to independently complete all scales and assessments.
6. Agreement from primary healthcare providers and patients to maintain current antidepressant treatment while adding agomelatine.

**Exclusion Criteria:**

1. Meeting criteria for other psychiatric disorders according to DSM-IV (except generalized anxiety disorder), such as schizophrenia, bipolar disorder, or mental disorders related to alcohol and drug dependence.
2. Current or previous history of brain organic diseases or loss of consciousness for more than 5 minutes.
3. Current or previous history of major physical diseases (including rheumatic immune system diseases, endocrine and metabolic diseases, nervous system diseases, etc.).
4. Current serious suicidal ideation or suicide attempt.
5. Pregnancy or lactation in women.
6. Color blindness (which would hinder neurocognitive testing).
7. Use of anticoagulants (e.g., heparin, warfarin), glucocorticoids, or treatment for thyroid diseases in the past 3 months.
8. Having received any neurocognitive assessment similar to this study in the past 12 months.
9. Positive urine drug screening results or abnormal thyroid function test.
10. Liver function tests showing transaminase (ALT and AST) levels 2 times above the upper limit of the normal range.
11. Electrocardiogram examination revealing a QTc ≥ 430 ms in males or QTc ≥ 450 ms in females.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Scale scores	Depression severity; higher scores mean a worse outcome.	Baseline (week 0), week 2, week 4, week 8
Side Effect Rating Scale (SERS) scores	Safety: frequency and severity of adverse events; higher scores mean a better outcome.	Baseline (week 0), week 2, week 4, week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Health Questionnaire (PHQ-9) scores	Self-report depression severity; higher scores mean a worse outcome.	Baseline (week 0), week 2, week 4, week 8
Hamilton Anxiety Rating Scale (HAMA) scores	Anxiety severity; higher scores mean a worse outcome.	Baseline (week 0), week 2, week 4, week 8
General Anxiety Disorder-7 (GAD-7) scores	Self-report anxiety severity; higher scores mean a worse outcome.	Baseline (week 0), week 2, week 4, week 8
Changes in Clinical Global Impression (CGI) scores	Symptom severity; higher scores mean a worse outcome.	Baseline (week 0), week 2, week 4, week 8
Snaith-Hamilton Pleasure Scale (SHAPS) scores	Self-reported severity of anhedonia; higher scores mean a worse outcome.	Baseline (week 0), week 2, week 4, week 8
Sheehan Disability Scale (SDS) scores	Self-report tool that assesses functional impairment in work/school, social life, and family life; higher scores mean a worse outcome.	Baseline (week 0), week 2, week 4, week 8
Quality of life (EQ-5D-3L) scores	Self-report Quality of life; higher scores mean a better outcome.	Baseline (week 0), week 2, week 4, week 8
performance of Neurocognitive test, including executive function, attention, processing speed, and memory	Neurocognitive function; higher scores mean a better outcome.	Baseline (week 0), week 2, week 4, week 8
Athens Insomnia Scale (AIS) scores	Self-report severity of insomnia; higher scores mean a worse outcome.	Baseline (week 0), week 2, week 4, week 8

Collaborators and Investigators

• Sponsor: Central South University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): January 30, 2023

Study Registration Dates

• First Submitted: October 9, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: major depressive disorder; antidepressant; augmentation; agomelatine; early-nonresponsive
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Agomelatine
• Other Study ID Numbers: Second Xiangya hospital

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No