The potential for drug-drug interactions in psychiatry and patients with epilepsy is very high. Moreover, antiepileptic drugs are widely used outside epilepsy as psychotropic agents and their spectrum of activity on behavior is of considerable interest to psychopharmacology. In both neurologic and psychiatric practice, pharmacotherapy combinations are commonly used to treat comorbid psychiatric and neurologic disorders, to reduce or control the adverse effects of a medication or to increase its efficacy. This paper focuses on the metabolic pharmacokinetic interactions between two classes of psychotropic drugs: antiepileptic and antipsychotic drugs. The degree of documentation varies for many interactions from clinical case-report experiences to well established research outcomes. The evidence and the clinical significance of these interactions are reviewed. In general, it is better to use as few drugs as possible, as multicolored politherapies increase the possible adverse effects of drug interactions and reduce patient compliance.