Physicians are often reluctant to use psychotropic medications in epilepsy patients with psychiatric disorders because of concern over the potential risk for lowering seizure threshold. This study assesses retrospectively the impact of psychotropic medications on seizure frequency in 57 patients seen consecutively at an epilepsy center. During psychotropic drug therapy, seizure frequency decreased in 33% of patients, was unchanged in 44%, and increased in 23%. Mean seizure frequency was not statistically different between pre-treatment and treatment periods (t = 0.23, df = 56). Simultaneous adjustments in antiepileptic drug regimen could not account for the findings. Results support the position that psychotropic medications, introduced slowly in low to moderate doses, can be safely used in epilepsy patients with comorbid psychiatric pathology during the regular course of clinical care.