Pharmacogenetics of Cytochrome P450 (CYP) 1A2 and Variability in Psychotropic Drug Response

Despite the availability of a wide range of different drug classes for the management of psychiatric disorders, the efficiency of drug treatment is far from optimal. Regardless of the initial choice and dose of standard psychiatric medication, about 30-50% of patients will not respond sufficiently to acute treatment while others suffer from severe adverse drug reactions. The patient-to-patient differences in drug response can be explained on the basis of variability in drug pharmacokinetic and pharmacodynamic processes. The involvement of the human polycyclic aromatic hydrocarbon (PAH)- inducible CYP1A2 in the metabolism of several psychotropic drugs is increasingly acknowledged. Currently, it is well-known that this enzyme shows a wide interindividual variability, but controversy has long surrounded the issue of a polymorphic distribution of the enzyme activity leading to pronounced differences in drug response. Moreover, whether genetic polymorphism and/or environmental factors play a definitive role has not yet unequivocally established. On the other hand, combination pharmacotherapy is commonly used in clinical psychiatry, and the CYP1A2 enzyme is the target of many clinically relevant drug interactions. This review is dealing with factors that could better explain patient-to-patient differences in drug response to psychotropic drugs, including CYP1A2 genetic polymorphisms, environmental factors as well drug interactions modulating the CYP1A2 enzyme activity.