Inclusion Criteria:
1. Male or female subjects aged 18-65 years, outpatients or inpatients.
2. Meets the DSM-V criteria for Severe Major Depressive Disorder ; a single episode（296.21、296.22、296.23）or recurrent episode （296.31、296.32、296.33）；
3. MADRS score greater than or equal to 24 in baseline；
4. HAMD-17 score greater than or equal to 20 in baseline.
5. Patients have learned and voluntarily participated in the study, and have to sign informed consent.
Exclusion Criteria:
1. Meets the DSM-V criteria for other mental disorder(schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, anxiety disorders, obsessive-compulsive and related disorders, somatic symptom and related disorders, etc ).
2. Patient has survived suicide attempt , or may have a significant risk for suicidal behavior ,or with a score of \>3 on suicidal thoughts item 10 on the MADRS.
3. Depressive episode of an organic mental disorder secondary to a systemic disease or a central nervous system disease, such as depressive episode secondary to hypothyroidism.
4. Serious and instable body disease such as cerebrovascular disease, respiratory disease, blood disease, liver and kidney disease, disease of internal secretion, nervous system and other systemic disease.
5. any history of seizures or other organic brain diseases.
6. History of alcohol or drug abuse (besides nicotine) over the last 6 months
7. Serious and instable body disease such as cerebrovascular disease, liver and kidney disease, disease of internal secretion (abnormal thyroid function), blood disease; any history of seizures or other organic brain diseases.
8. Subjects who can't take drug or have an operation history which affect drug metabolism.
9. Clinically significant changes in ECG or laboratory tests, including \>1.5X upper limit of normal liver function、over the limit of normal renal function and blood sugar、abnormal cardiac troponins、obvious abnormity in the thyroid function
10. Pregnant or lactating women and women of childbearing potential throughout the study period; men who have the desire of fertility within three months;
11. Participation in other clinical studies in the nearly 1 month before screen.
12. Other conditions which, in the investigator's judgment, render patients unsuitable for the clinical study.
