OBJECTIVES: To determine the cost-effectiveness of agomelatine for major depression in adults. METHODS: A hypothetical cohort was simulated from a discrete event simulation (DES) model developed to describe the course of disease in individuals. Model inputs included Thai data on disease parameters and costs while impact measures are derived from systematic reviews and meta-analyses of the international literature. The costs for treatment of adverse events of these drugs, insomnia and sexual dysfunction, were taken into account in the model. Antidepressant drugs were analyzed for treatment of episodes (12-24 weeks) plus a continuation phase (6-9 months) and for maintenance treatment over 2 years of follow up. Results are presented as Thai Baht cost (THB) per quality adjusted life year (QALY) gained, compared to a matrix comparators (50 % venlafaxine and 50% escitalopram). RESULTS: Preliminary results show that daily costs for average dose of agomelatine (25 mg), escitalopram (10 mg) and venlafaxine (150 mg) are 52, 60, 98 THB, respectively. Total cost of agomelatine is 52,000 THB and total cost of matrix comparator is 76,000 THB. Health benefit measures of agomelatine and the matrix comparator are almost the same at 2,500 QALY gained. Agomelatine is considered a cost-effective intervention with an ICER of 400,000 (95% uncertainty range: 410,000- 390,000) THB per QALY gained. The ICER is less than three times Gross Domestic Product (GDP) per capita in Thailand of 420,000 THB. CONCLUSIONS: Agomelatine is the most cost-effective treatment option for episodic continuation and maintenance treatment of major depression when compared with venlaflaxine and escitalopram. As recommended by the World Health Organization (WHO) for cost-effectiveness health intervention, agomelatine is an affordable option for treatment of major depressive episodes in Thailand.