Epilepsy is a common disabling neurological disorder associated with increased rates of mood disorders especially depression as compared to the general population. Most antidepressants at therapeutic dosages exhibit a seizure risk. Some antidepressants may also display antiepileptic effects, especially at low doses, but the mechanism of this action is largely unknown. In general, the new antidepressants that selectively inhibit the reuptake of serotonin may cause an increase in plasma concentrations of antiepileptic drugs. On the other hand, phenobarbital, phenytoin and carbamazepine stimulate the catabolic degradation of tricyclic antidepressants and tricyclic antidepressants have an inhibitory effect on the elimination of antiepileptic drugs. This article refers to the relevance of interactions between antiepileptic drugs and antidepressant drugs in the treatment of mood disorders in patients with epilepsy.