OBJECTIVES: The objective of this exploratory analysis was to assess the cost-effectiveness of quetiapineXR as monotherapy compared to other key drug treatments in MDD patients, who have failed on previous therapy. METHODS: A Markov Model with one week cycles was used  to assess the cost effectiveness of quetiapineXR treatment over 52 weeks. Key outcomes were: response rates, costs and Incremental Cost-Effectiveness Ratios (ICERs) for second line monotherapy. The obtained clinical trials data for all drugs represented first line therapy for MDD.  For this reason, response rates were down-adjusted to reflect their use as a second-line therapy, with each response rate being multiplied by a factor obtained from the STAR*D-  trial. Since response rates were reported at a constant rate in clinical trials, they were converted into “weekly probabilities” of response. Patients entering second-line monotherapy were not differentiated by switch or add-on. QuetiapineXR(150mg) was compared with venlafaxineXR(150mg), escitalopram(10mg) and bupropionXL(300mg), which are considered to be the most relevant monotherapy comparators in Turkey. One-way sensitivity analyses were conducted on key model parameters to evaluate the robustness of the model. RESULTS: The response rates  at any time over 52 weeks were 22.5% for quetiapineXR, venlafaxineXR 17.8%, escitalopram 12.6% and bupropionXL 10.7%. In terms of incremental cost per additional second-line responder, quetiapineXR was found to be dominant (more effective and less costly) versus venlafaxineXR (-353.55€) and quetiapineXR was cost-effective (more effective and more costly) versus escitalopram (1785.43€) and bupropionXL (652.90€). The cost per responder of quetiapineXR(48.85€) was less than venlafaxineXR(62.68€), escitalopram(73.20€) and bupropionXL(95.52€). CONCLUSIONS: This exploratory analysis demonstrated that in patients with MDD who have failed on previous antidepressant therapy, quetiapineXR 150mg as monotherapy was found to be cost-effective compared to escitalopram and bupropionXL, in terms of cost per responder, and was dominant when compared to venlafaxineXR, demonstrating higher efficacy at lower costs.