OBJECTIVES: Antipsychotic treatments can cause several side effects, such as weight gain, metabolic syndrome, which could lead to cardiovascular complications (CVC). A number of models are available for the evaluation of the economic impact of antipsychotics in schizophrenia, but few of them properly consider metabolic syndrome and associated complications. The objective of this study was to build a new model to reflect the real patient therapeutic management of patients with schizophrenia. METHODS: An expert meeting was set up to validate the design of the model, and to list all outcomes that should be included in the model structure. The model was programmed in Excel 2010, with VBA coding. RESULTS: The expert meeting validated the premise that the aim of the treatment is to prevent relapses, affecting patients’ quality of life and generating substantial costs. A patient-level Markov model structure was used, to simulate a cohort of patients with schizophrenia over lifetime, with 6-month cycles. Five lines of treatments are considered in the model. With up to 3 comparators in the first cycle, it models patients’ treatment adjustment, and provides the flexibility to specify at any line of treatment a specific distribution of antipsychotics. The model considers treatment response, associated side effects (weight gain, sexual dysfunction, EPS and sedation), diabetes diagnosis and CVC (coronary heart disease and stroke). Non-response and compliance (based on side effects) drive relapse and hospitalization. Each relapse is assumed to require a treatment switch. Patients are also allowed to escape from the healthcare system, or to die, due to natural death, suicide or CVC-related death. Finally, extensive deterministic and probabilistic sensitivity analyses are also implemented. CONCLUSIONS: This new economic model allows taking into account all key features of schizophrenia, in a transparent way.