This is a single-center, double blind, randomized, placebo-controlled, parallel group study of bear bile pill, as add-on therapy in MDD patients conducted in Shang Hai Mental Health Center. The purpose of this study is to determine the efficacy and safety of bear bile pill in reducing symptoms of depression in Major Depressive Disorder (MDD)patients with inadequate response to current antidepressant therapy. Following a screening period, subjects who meet the entry criteria will be randomized to treated with either placebo or 450mg bear bile pill three times daily for 8 weeks.

Inclusion Criteria:

1. Meets the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition, Text Revision (DSM-V) criteria for Major Depressive Disorder (MDD); a single or recurrent episode without psychotic features ;Codes are as follows: F32.0、F32.1、F32.2、F33.0、F33.1 、F33.2.
2. Outpatients or inpatients.
3. Male or female subjects aged 18-65 years.
4. Patients have got standard treatment of SSRI/SNRI monotherapy for more than 4 weeks in current episode of depression before trial entry.
5. MADRS score greater than 20.
6. Women of childbearing potential must be willing to use acceptable methods of contraception throughout the study period and the following one month.
7. The patient the patient fully understand and signed the informed consent form

Exclusion Criteria:

1. Patient has survived a suicide attempt or has acute suicidal tendencies (MADRS Item 10 > 4).
2. Comorbidity according to DSM-V, axis I except major depressive disorder.
3. Failed 3 or more adequate antidepressant courses in current episode of depression.
4. MADRS reduction ratio ≥25% within one week from the screening to the baseline Visit.
5. Depressive episode secondary to psychiatric illness or somatic disease.
6. 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.
7. History of alcohol or drug abuse over the last 6 months
8. Allergic history to bear bile pills, or serious drug allergic history.
9. Pregnant or lactating women and women of childbearing potential throughout the study period; men who have the desire of fertility within six months;
10. 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
11. Treatment with MECT or rTMS in nearly three months.
12. Treatment with a systematic psychological treatment in nearly three months.