Should antidepressant drugs of the selective serotonin reuptake inhibitor family be tested as antiepileptic drugs?

For a long time, there has been a misconception that all antidepressant drugs have proconvulsant effects. Yet, antidepressants of the selective serotonin reuptake inhibitor (SSRI) family not only have been shown to be safe when used in patients with epilepsy (PWE) but also have been found to possess antiepileptic properties in animal models of epilepsy. In humans randomized to SSRIs vs. placebo for the treatment of major depressive episodes, the incidence of epileptic seizures was significantly lower among those treated with the antidepressants. These data raise the question of whether there is enough evidence that would support a randomized placebo-controlled trial to test antiepileptic effect of SSRIs in PWE. This article reviews the preclinical and clinical data to address this question.