The concomitant use of multiple therapeutic agents in the treatment of resistant affective and obsessive-compulsive disorders increases the likelihood of a patient experiencing a drug-drug interaction at either the pharmacokinetic or pharmacodynamic level. Recent developments in molecular biology and pharmacogenetics have allowed the identification of which psychotropic agents are substrates, inducers, or inhibitors of specific hepatic cytochrome P450 isozymes. This increases the predictability of which drug combinations may lead to kinetic interactions. However the individual variability in kinetic disposition and pharmacodynamic response still limits the predictability of a drug-drug interaction in an individual patient treated with polytherapy.