Epilepsy is a chronic disorder that adversely affects social, vocational, and psychological functioning. Despite the variety and complexity of the negative clinical associations with epilepsy, depression is remarkable in prevalence and related adverse effects on health status. An estimated 30-50% of persons with refractory epilepsy have major depression, and depression has a stronger correlation than seizure rate with quality of life. Suicide is one of the leading causes of death in epilepsy. Available data indicate that depression may result from underlying brain dysfunction rather than social and vocational disability. Most patients with depression are not screened systematically for the diagnosis, and are subsequently not treated. Although the density of serotonin receptors is greatest in limbic brain regions commonly involved in human epilepsy, such as the mesial temporal and prefrontal areas, no prior randomized controlled trials have evaluated the efficacy of serotonin reuptake inhibitors for depression in epilepsy.