OBJECTIVES: To simulate the optimal budget allocation for first line antipsychotic medications in schizophrenia which minimize relapses.  METHODS: From the health system perspective, a Lagrange budget optimization analysis was performed with the SOLVER application in order to estimate the efficient market share of first line antipsychotics (oral, depot and Long Acting Injectable - LAI). The following parameters were gathered and validated in five psychiatric institutions: target population, current market share, adherence to the treatment, risk of relapse, and the usage of outpatient and inpatient care resources. The tariffs were taken from official and institutional sources. The time frame was one year. Two scenarios were compared: the current and the optimum. RESULTS: Current scenario: assuming a budget constraint of USD 250,000, a target population of 381 patients and a baseline market share (oral 95.7%, depot 2.3% and LAI 2.0%), 150 relapses were avoided (savings of USD 320,086). With the Optimum scenario market share [oral 83.0%, depot 4.0% and LAI 13.0%], 208 relapses were avoided [savings of USD 445,986].  CONCLUSIONS: Assuming a fixed budget for first line antipsychotic treatments, increasing the usage of LAI enable a budget optimization and relapses minimization.