OBJECTIVES: CYP450 enzyme activities have been associated with inter-individual variability affecting efficacy and tolerability among non-psychotic major depressive disorder (MDD) patients.  Pre-prescription pharmacogenetic testing helps to identify patients with increased risk for adverse reactions, lack of efficacy and increased hospitalization costs.  These test results could assist doctors to prescribe alternative therapy or optimum doses. Present study is to estimate the cost effectiveness of pre-prescription pharmacogenetic testing to assess the CYP450 enzyme activity for the treatment of depression using selective serotonin reuptake inhibitors (SSRIs). METHODS: Markov model was developed from societal perspective to identify cost and quality adjusted life months (QALM) gained for carrying out pharmacogenetic testing compared to no test strategy.  A systematic search of the literature was carried out to identify published evidence for associations between adverse events, dropout rates and the three phenotypic groups: ultrafast metabolizers, poor metabolizers and intermediate metabolizers. Potentially relevant papers were used to derive the transitional probabilities, costs and sensitivity as well as specificity of CYP450 enzyme testing technique. Multiple one-way sensitivity analyses were performed to find the robustness of the model. RESULTS: Projected outcomes associated with pre-prescription CYP450 testing strategy for a patient with MDD was $4367/6.5 compared to $5634/6.4 QALM in no test strategy. The testing strategy was found to be dominant between the above two options. The model was found to be sensitive to utility values, cost of adverse events follow up, percentage of ADR dropouts and remission rates. CONCLUSIONS: The study results indicate that CYP450 genotype-guided SSRI treatment for depression is potentially cost saving and leads to improved quality of life in patients. Yet the model is not robust with respect to selected clinical and economic variables.  Further studies should be pursued to confirm the value of genotype-guided therapy before broadly applying in the regular clinical practice