Genotypes of cytochrome P450 and clinical response to clomipramine in patients with major depression.
The genetic cytochrome P450 polymorphism is reported in factors affecting the individual response to drugs. The interindividual variation at steady-state levels or also in elimination of drugs, finds an explanation in genetic differences in the metabolism. In particular, activities of the P450-IID6 isoenzyme are related to the sparteine/debrisoquine oxidation polymorphism. Phenotyping such a system has been proposed to analyse variability in the tricyclic antidepressant level. To analyse clinical relevance of a pharmacogenetic approach, we studied the cytochrome P450 CYP2D6 genotypes and the clinical responses to clomipramine in 21 hospitalised patients who met DSM-III-R criteria for major depression. Three patients were predicted as poor metabolizers. We suggested a limitation of clomipramine (CMI) hydroxylation in poor metaboliser (PM) patients which is balanced by a desmethylation. The clinical efficacy pattern does not differ in poor metaboliser and early metaboliser patients. Firstly, there is no significant differences in the evolution of scores on MADRS and specific retardation scale into the two groups. Secondly, outcome of side effects does not occur more frequently in PM patients. Clinical relevance of such an approach needs further study.
Bouchez
J
J
Adult Psychiatry Department, University Hospital of Lille, 59037 Lille, France.
Dumur
V
V
Lhermitte
M
M
Goudemand
M
M