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.

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.

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