OBJECTIVES: To compare the cost-effectiveness of escitalopram with generic citalopram and venlafaxine in the treatment of Major Depressive Disorder (MDD) in Turkey. METHODS: A decision analytic model with a six-month horizon was adapted to the Turkish setting. All patients (aged = 18 years) were treated by a psychiatrist over a period of six months. Model inputs included drug-specific probabilities from head-to-head trial data, literature, and expert opinion. A national survey was conducted among psychiatrists (n=90; response rate=96.7%) to obtain patterns of clinical management, resource utilization and lost productivity data (all weighted by practice size). The main outcome measure was success [i.e., remission defined as Montgomery-Åsberg Depression Rating Scale (MADRS) score =12] and costs (in US$ 2004) of treatment (i.e., costs of drugs and medical care). The analysis was performed from the governmental and societal perspectives. Human capital approach was used to estimate the cost of lost productivity using the minimal industrial wage in Turkey. RESULTS: Treatment with escitalopram yielded lower expected costs and greater effectiveness compared with citalopram. The expected success rate was higher for escitalopram [63.2% (CI95 61.1%-65.3%)] compared with generic citalopram [57.6% (CI95 55.3%-59.9%)]. From the governmental perspective, total expected costs were US$297 (US$282-US$313) for escitalopram and US$305 (US$288-US$322) for generic citalopram. From the societal perspective the costs per patient were US$678 (US$653-US$705) for escitalopram and US$709 (US$682-US$736) for generic citalopram. For venlafaxine, a similar success rate compared with escitalopram but higher total costs were found from both the governmental (i.e, 23.5%) and societal (i.e, 9.3%) perspectives. Multivariate sensitivity analyses on unit costs and probabilities demonstrated the robustness of the results. CONCLUSION: Escitalopram is a cost-effective alternative compared to (generic) citalopram and a cost saving alternative compared with venlafaxine in the treatment of MDD in Turkey.