OBJECTIVE: Death by suicide among patients with epilepsy has found scant psychiatric attention, yet it may occur at the rate reported among patients with manic-depressive illness. We aim to clarify the psychopathology and pathogenesis of suicide in epilepsy and to document an effective method of prevention.METHOD: A total of 10,739 patients with epilepsy were seen at the Epi-Care Center in Memphis from 1987 to 1999. The patients with significant psychiatric complications were evaluated systematically and treated with an increasingly effective psychopharmacologic approach.RESULTS: Five suicides were registered during the 12-year period. All occurred in patients with longstanding complex partial seizures and dysphoric disorder a short time after full control of the seizures was achieved. During the last 8years of the 12-year period, more effective pharmacotherapy of the psychiatric complications of epilepsy was used (augmented antidepressant medication), and the two suicides that still occurred had eluded this treatment. Review of earlier series confirms that suicide tends to occur particularly among patients with chronic epilepsy who have obtained good control of their seizures; suicide may occur during interictal dysphoric episodes with or without psychotic features or in a state of postictal depression.CONCLUSIONS: Suppression of seizures in longstanding epilepsy may be associated with suicidal risk. The psychotoxic effect of predominant inhibitory mechanisms appears to be the crucial pathogenetic factor in all suicides. The number of suicides in our series is a fraction of that expected based on previous reports and indicates that prevention by psychopharmacologic treatment is available.