OBJECTIVES: Major Depressive Disorder (MDD) is a chronic illness associated with major burden on Quality-of -Life (QoL) and health care resources. A recent study estimated annual cost being €282 per European inhabitant. Adjunctive treatments with aripiprazole, quetiapine and olanzapine have demonstrated efficacy in patients with MDD that respond insufficiently to antidepressant treatment. The objective is to estimate the cost-effectiveness of adjunctive therapies in depressive patients failing to respond to antidepressant therapy in Turkey. METHODS: An economic model was built simulating MDD patients between major depressive episodes (MDEs) and remission over lifetime. During MDEs, patients were treated with adjunctive aripiprazole, quetiapine or olanzapine. Patients who did not respond at 6 weeks switched to subsequent treatment lines. Comparative effectiveness between aripiprazole, quetiapine and olanzapine, was imputed using an indirect comparison combining 6-week published studies. Resource use data and unit costs were obtained from Turkish studies. RESULTS: Over life-time, aripiprazole patients spent less time in MDEs compared to quetiapine (7,7 weeks) and olanzapine (7.5 weeks). Compared to Quetiapine, patients with aripiprazole showed improvement in QoL (+ 0.045 QALY) at incremental direct cost of 421TL. Compared to olanzapine, patients with aripiprazole dominated, meaning improvement of QoL (+0.042 QALY) respectively, at lower direct cost (-32 TL), despite higher drug costs. Sensitivity analyses estimated a 87% likelihood that aripiprazole improved QoL at a comparable cost verus quetiapine and 88% versus olanzapine. CONCLUSIONS: This is the first lifetime health-economic model in Turkey taking patient heterogeneity into account when assessing QoL and costs of different adjunctive strategies in MDD. These results indicate that adjunctive treatment with aripiprazole provides health benefits at lower costs compared to quetiapine and olanzapine, in patients with MDD.