[Role of pharmacogenetics in psychopharmacotherapy]

Abstract

Genetic polymorphism related to certain P450 isozymes, in particular the sparteine/debrisoquine oxygenase, is the dominant cause of interindividual variation in elimination of several drugs. If the pharmacokinetic variability is large, relative to the therapeutic index of the drug, the genetic polymorphism will be clinically important. If the dose cannot be adjusted on the basis of effect measurements, phenotyping may be a supplement or replacement for drug level monitoring which is otherwise relevant for such drugs. Several aspects as elucidated by the experience with the sparteine/debrisoquine oxidation polymorphism ought to be analysed: The role of active metabolites and their rate of formation and elimination, selective drug-drug interaction at the polymorphic isozyme or at alternative routes of elimination, the possible role of two or more polymorphic drug oxidation pathways, and the effect of saturable kinetics. The sparteine/debrisoquine oxidation polymorphism affects two major classes of drugs in psychopharmacology, the antidepressants and the neuroleptics, and this is the best example of clinical relevance of pharmacogenetic polymorphism. Routine use of phenotyping thus should be considered for psychiatry departments.