A simulation model based on the theory of clinical decision analysis was used to compare outcomes and costs when treating patients with major depressive episodes using either a selective serotonin re-uptake inhibitor (SSRI) or a tricyclic antidepressant (TCA), in comparison with milnacipran (a serotonin), and a norepinephrine re-uptake inhibitor (SNRI). The clinical data used were taken from published meta-analyses. This analysis supports: (1) a comparable efficacy of milnacipran and TCA with a better tolerance; and, (2) an advantage of milnacipran over SSRI for efficacy with a comparable tolerance. Based on these findings, a decision tree was constructed with the assistance of a panel of psychiatrists in order to provide a model of usual clinical practice. Estimates not available from clinical studies were obtained either from literature analysis or from the panel.

Economic appraisal was performed according to the viewpoint of the French national sickness fund (sécurité sociale), and expenditure assessment was limited to direct costs (hospitalizations, antidepressant medications, visits, and laboratory tests). The results suggest that milnacipran is a cost-effective alternative: the expected cost of treatment per depressive episode is lower than either a French representative panel of TCAs (a saving of 288 FF), or SSRIs (a savings of 961 FF). The expected length of clinical remission is slightly higher than comparators. The robustness of these findings was supported by sensitivity analyses.