Inclusion Criteria:

• 1.Male or female patients.
• 2.18 to 64 years of age.
• 3. Inpatients or outpatients.
• 4. Written informed consent from the patient and/or legally authorized representative.
• 5. Able to comply with the protocol and follow written and verbal instructions.
• 6. Subjects of childbearing potential must have a confirmed negative serum b-hCG test prior to entry into Segment B and must employ an acceptable method of birth control (e.g., oral, depot, or implanted contraceptive method, IUDs, sterilization, barrier methods in conjunction with spermicide).
• 7. Diagnosis of major depressive disorder, as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision criteria and confirmed by the semi-structured Mini International Neuropsychiatric Interview (MINI), recurrent episode for at least one month prior to the entry.
• 8. Minimum total score of 22 on the Montgomery-Asberg Depression Rating Scale (MADRS).

Exclusion Criteria:

• 1.Patients whose current depressive episode is diagnosed with psychotic features, catatonic features, seasonal pattern or post-partum onset.
• 2.The duration of the current depressive episode is greater than 2 years.
• 3.Patients who are currently suicidal or have a history of a suicide attempt within 3 years prior to entry.
• 4.Patients whose current depressive episode is secondary to a general medical disorder.
• 5.Patients with a history or presence of bipolar disorders or psychotic disorders according to the D and L criteria of the MINI.
• 6.Patients with alcohol dependence or abuse or substance dependence or abuse in the past 12 months except nicotine or caffeine dependence.
• 7.Patients with a history of failure to respond to treatment with paroxetine or other antidepressant medications.
• 8.Patients who have used the following prior to entry into Segment B: any antipsychotic within 3 months,-fluoxetine within 35 days, -any monoamine oxidase inhibitor within 21 days, any other antidepressant, anxiolytic, sedative-hypnotic, or mood-stabilizer (lithium, anticonvulsants) within 7 days except permitted concomitant medications.
• 9.Females who are pregnant or breast-feeding.
• 10.Severe or unstable cardiovascular, renal, hepatic, respiratory, hematological, endocrinological, neurological, or other somatic disease that might interfere with the evaluation of study medication.
• 11.History of seizures other than a single childhood febrile seizure.
• 12.ECG abnormalities of potential clinical significance including a QT interval with Bazett’s correction of 500 msec or more at entry.
• 13.Use of known inducers or potent inhibitors of CYP3A4 within 7 days of entry.
• 14.Use of drugs with known risk for Torsade de Pointes within 7 days of entry into Segment B.
• 15.Participation in a clinical trial of an experimental therapy within 30 days prior to entry or prior participation in a clinical trial of saredutant.
• 16.Patients with a positive HbsAg or anti-HCV antibody test at screening.
• 17.Patients with any of the following at screening: ALT >2 times the upper limit of the normal range (XULN), AST >2XULN, GGT >3XULN, total or conjugated bilirubin >ULN.