Clomipramine, fluoxetine and CYP2D6 metabolic capacity in depressed patients.
Cytochrome P450-2D6 may be involved in the metabolism of many drugs such as psychotropic drugs and its genetic polymorphism is responsible for inter-individual differences in the therapeutic effect and toxicity of these drugs. Moreover with the same genetic basis, CYP2D6 metabolic capacity variations are observed. Different factors of variation may be involved, among them the prescribed drugs. The aim of this study was to compare the influence of two types of antidepressants, tricyclic (clomipramine) and serotonergic specific recapture inhibitor (SSRI) (fluoxetine), on the CYP2D6 metabolic capacity of depressed inpatients. The CYP2D6 phenotype (dextromethorphan test) was determined in 56 genotyped (PCR-SSCP) depressed caucasian inpatients with a heterozygous genotype. Forty-five subjects were treated with clomipramine and eleven received fluoxetine. The dextromethorphan metabolic ratio (MR) median was significantly higher in the fluoxetine group (0.255) than in the clomipramine group (0.083, p < 0.014). In this study, fluoxetine involved a greater decrease of CYP2D6 metabolic capacity than clomipramine. Clinical implications and the possible connection between a decreased CYP2D6 activity and adverse drug effects were discussed. Caution should be taken when drugs with a low therapeutic index must be coprescribed in such patients.
Vandel
P
P
Fédération de Psychiatrie et Psychologie Médicale, Centre Hospitalo-Universitaire, 25030 Besançon, France. pvandel@chu-besancon.fr
Haffen
E
E
Nezelof
S
S
Broly
F
F
Kantelip
J P
JP
Sechter
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D002997:Clomipramine / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D005473:Fluoxetine; D019389:Cytochrome P-450 CYP2D6; D002997:Clomipramine