[Pharmacogenetics of antidepressant metabolism. Value of the debrisoquin test]

The drug monitoring of antidepressants in blood plasma has revealed considerable interindividual differences in steady-state levels. For some compounds recent results strongly suggest that this phenomenon finds an explanation in genetic differences in the metabolism of the drugs by monooxygenases (cytochrome P-450) in the liver. Thus, a genetic deficiency has been described in 5-10% of the European population in the metabolism of debrisoquine and sparteine. Clinical experience shows that the separation of subjects into extensive metabolizers (EM) and poor metabolizers (PM) is also valid for drugs of interest in psychiatry, such as some betablockers and antidepressants like amitriptyline, nortriptyline and desipramine. Actually, PMs of debrisoquine may develop excessively high levels of these antidepressants in blood during the treatment. On the other hand, it is probable that, at least, one oxidative pathway of maprotiline belongs to the genetic polymorphism of debrisoquine, but a deficiency in the metabolism of this test substance does not necessarily mean high levels of maprotiline. Today's clinical experience shows that, in some cases, PMs of debrisoquine do not respond to a treatment with nortriptyline. However, this has not been demonstrated for amitriptyline. It is predicted that pharmacogenetic tests will find their place in psychopharmacotherapy, especially for subjects candidates for a long-term treatment or susceptible to suffer from side effects. However, the validity of the test remains to be demonstrated for other drugs, like benzodiazepines and neuroleptics, but also in the case of patients suffering from organic diseases or under treatment with potential competitors.