Antidepressant Drugs for Seizures and Epilepsy: Where do we Stand?

People with epilepsy (PWE) are more likely to develop depression and both these complex chronic diseases greatly affect health-related quality of life (QOL). This comorbidity contributes to the deterioration of the QOL further than increasing the severity of epilepsy worsening prognosis. Strong scientific evidence suggests the presence of shared pathogenic mechanisms. The correct identification and management of these factors are crucial in order to improve patients' QOL. This review article discusses recent original research on the most common pathogenic mechanisms of depression in PWE and highlights the effects of antidepressant drugs (ADs) against seizures in PWE and animal models of seizures and epilepsy. Newer ADs, such as selective serotonin reuptake inhibitors (SRRI) or serotonin-noradrenaline reuptake inhibitors (SNRI), particularly sertraline, citalopram, mirtazapine, reboxetine, paroxetine, fluoxetine, escitalopram, fluvoxamine, venlafaxine, duloxetine may lead to improvements in epilepsy severity whereas the use of older tricyclic antidepressant (TCAs) can increase the occurrence of seizures. Most of the data demonstrate the acute effects of ADs in animal models of epilepsy while there is a limited number of studies about the chronic antidepressant effects in epilepsy and epileptogenesis or on clinical efficacy. Much longer treatments are needed in order to validate the effectiveness of these new alternatives in the treatment and the development of epilepsy, while further clinical studies with appropriate protocols are warranted in order to understand the real potential contribution of these drugs in the management of PWE (besides their effects on mood).