OBJECTIVES: A cost-utility analysis of a new antidepressant agomelatine (Valdoxan) compared to generic venlafaxine and placebo in the treatment of MDD was performed from the Finnish societal perspective. METHODS: The analysis is based on a Markov state transition model with second-order Monte Carlo simulation and two year time-frame. Conservatively, agomelatine and venlafaxine were assumed to be equally effective in the treatment of depressive symptoms, but to differ in costs, side effect profiles, clinically significant sleep disorders during treatment, discontinuation rates and discontinuation symptoms based on agomelatine clinical trials. Finnish EQ-5D utilities, health care resource use, travelling and production losses (derived from the actual work rates of MDD patients using human capital approach) were estimated based on a Finnish study including 298 patients with MDD, adjusted for confounders (age, gender, marital status, income and education), and matched to model states and adverse events using two-stage multivariate models. The costs were presented in 2008 value. Annual discounting rate considered was 3%. RESULTS: Compared to generic venlafaxine and placebo the treatment with agomelatine resulted in 0.012 and 0.066 additional quality-adjusted life-years (QALY) gained, and in 356 and -€126 additional treatment costs during the two year time-frame, respectively. The corresponding additional costs including production losses were 220 and -€3255. Agomelatine was associated with an incremental treatment cost of €29,000/QALY gained compared to generic venlafaxine. When production losses were included, this ratio fell to €18,000/QALY gained. According to cost-effectiveness acceptability frontier (excl. production losses), the probability of agomelatine’s cost-effectiveness was 57 and 90% with the willingness-to-pay levels of €30,000 and €50,000 per QALY gained, respectively. Agomelatine dominated placebo. One-way sensitivity analyses showed that the results were robust to key parameter changes. CONCLUSIONS: Agomelatine is a cost-effective treatment for MDD versus generic venlafaxine and dominant versus placebo based on the representative Finnish data.