The purpose of the study is to establish the optimum treatment strategy for first-line and second-line antidepressants in the acute phase treatment of major depression.

Inclusion Criteria:

• non-psychotic unipolar major depressive episode (Diagnostic and Statistical Manual, Fourth Edition [DSM-IV]) in the preceding month
• age 25-75
• starting treatment with sertraline clinically indicated
• tolerability to sertraline 25 mg/d ascertained
• can understand and sign informed consent form
• can be contacted by telephone for symptom severity and adverse events

Exclusion Criteria:

• have received antidepressants, mood stabilizers, antipsychotics, psychostimulants, electroconvulsive therapy (ECT) or depression-specific psychotherapies in the preceding month
• history of schizophrenia, schizoaffective disorder or bipolar disorder
• current dementia, borderline personality disorder, eating disorder or substance dependence
• physical disease interfering with sertraline or mirtazapine treatment
• allergy to sertraline or mirtazapine
• terminal physical illness
• currently pregnant or breast-feeding
• high risk of imminent suicide
• requiring compulsory admission
• expected to change doctors within 6 months
• cohabiting relatives of research staff
• cannot understand Japanese