Drug-resistant epilepsy: Is there an overlooked association between drug resistant epilepsies and neuropsychiatric comorbidities?

Despite the introduction of several first-in-class antiseizure medications in the last 15 years and the recent generation of new hypotheses to explain the drug-resistant phenotype in epilepsy, the proportion of patients with refractory epilepsy remains apparently unchanged. Therefore, it is essential to provide new perspectives (or, perhaps, revive old perspectives) to develop more effective therapeutic interventions. Some of the complex comorbid disorders associated with epilepsy, which present similar rates of unresponsive patients and whose refractoriness is possibly mediated by similar causes, could provide keys to implement novel therapeutic interventions. In this article, based on Swanson's ABC model to develop scientific hypotheses, we establish (or rescue) some interesting connections between depression and epilepsy, focusing on the relationship between drug-resistant epilepsy and depression.