Depression is frequent, underdiagnosed, and untreated in people with epilepsy. The lack of treatment is partially explained by the concerns over the proconvulsive effects of psychoactive drugs. There are few studies on the effects of selective serotonin reuptake inhibitors (SSRIs) in adults with epilepsy and none in children. The main purpose of the present study was to analyze the impact of SSRIs on the severity and frequency of seizures in children and adolescents with epilepsy and major depressive disorders. In addition, we also evaluated the efficacy of SSRIs in the treatment of depressive symptoms and side effects other than seizure aggravation.