The risk of depressive and anxiety disorders is increased among patients with epilepsy, but it is not known whether patients are treated with antidepressants in clinical practice. In a nationwide case register linkage study, all patients who received a main diagnosis of epilepsy or osteoarthritis on first admission or outpatient contact during the period 1995 to 2000 in Denmark were identified, and rates of subsequent purchases of antidepressants were calculated. Comparisons were also made with a gender-, age-, and calendar-matched sample of the general population. Patients diagnosed with epilepsy had a 1.73 (95% CI: 1.45-2.06) times increased rate of subsequently purchasing antidepressants, compared with patients diagnosed with osteoarthritis and a 2.44 times (95% CI: 2.12-2.81) increased rate compared with the rate among the general population. It is concluded that patients with epilepsy have a moderately increased probability of being prescribed antidepressants in clinical practice.