Table 1 Eligibility criteria

(1) The participant fulfils criteria for non-psychotic unipolar major depressive episode (DSM-IV) within 1 month before starting sertraline

1) Having taken antidepressants, mood stabilizers (lithium, valproate, carbamazepine, lamotrigine), antipsychotics, psychostimulants (methylphenidate, pemoline, atomoxetine), electroconvulsive therapy, rTMS, light therapy, or depression-specific psychotherapies (cognitive-behaviour therapy, interpersonal therapy) within 1 month before starting sertraline

(2) Age between 25 and 75 on the day when sertraline is started

(2) History of schizophrenia, schizoaffective disorder or bipolar disorder (DSM-IV) as judged by treating physician

(3) The major depressive episode is the focus of the treatment and the treating physician has judged sertraline to be its appropriate first-line drug

(3) Current dementia, borderline personality disorder, eating disorder or substance dependence (DSM-IV) as judged by treating physician

(4) Tolerability to sertaline has been ascertained after 3–16 days of treatment with sertraline 25 mg/day

(4) Physical diseases that may contraindicate treatment with sertraline or mirtazapine

(5) The participant is able to understand and sign written informed consent

(5) Allergy to sertraline or mirtazapine

(6) The participant is available on the phone for assessment of symptoms and side effects

(6) Terminal physical diseases

(7) Women who are pregnant or breastfeeding (if there is a possibility of getting pregnant within 6 months of trial entry, participation is allowed only after providing signed consent to avoid pregnancy during the trial period)

(8) Imminent high risk of suicide as judged by treating physician

(9) Needing non-voluntary hospitalisation

(10) High probability of changing hospital due to relocation, etc., within 6 months of trial entry

(11) Cohabiting family members of research staff members of the trial

(12) Inability to understand written Japanese