Depression is a very prevalent and complex disease. This condition is associated with a high rate of relapse, making its treatment a challenge. Thus, an intensive investigation of this disease and its treatment is necessary. In this work, through cell viability assays (MTT and neutral red assays) and alkaline comet assays, we aimed to test the induction of stress in human SH-SY5Y cells through the application of hydrocortisone and hydrogen peroxide and to test the reversal or attenuation of this stress through the application of mirtazapine to the cells. Our results demonstrated that hydrogen peroxide, and not hydrocortisone, can induce cellular stress, as evidenced by DNA damage and a global cellular viability reduction, which were alleviated by the antidepressant mirtazapine. The establishment of a cellular model of depression through stress induction is important to study new possibilities of treatment of this disease using cell cultures.