Citalopram: an interaction study with clomipramine in a patient heterozygous for CYP2D6 genotype.
A pharmacokinetic interaction between the selective serotonin reuptake inhibitor citalopram and a tricyclic antidepressant, clomipramine, was noted in a patient treated for major depression and obsessive-compulsive disorder. After the addition of citalopram, a desmethylclomipramine plasma level increase and an 8-hydroacy-desmethylclomipramine plasma level decrease were observed. The CYP2D6 phenotype, determined when the patient received the antidepressant comedication, characterized a poor metabolizer status (dextromethorphan metabolic ratio >0.3), despite a heterozygous genotype containing a wild-type allele with extensive metabolic capacity and a mutant non-functional allele (CYP2D6*1A/CYP2D6*4A). This case seems to be one of the first descriptions of the clinical relevance of a CYP2D6 heterozygous genotype in a patient treated with antidepressant.
Haffen
E
E
Department of Clinical Psychiatry and Medical Psychology, University Hospital of Besançon, France. emmanuel.haffen@ufc-chu.univ-fcomte.fr
Vandel
P
P
Broly
F
F
Vandel
S
S
Sechter
D
D
Bizouard
P
P
Bechtel
P R
PR
D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015283:Citalopram / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002997:Clomipramine / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000523:psychology; D010641:Phenotype
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; C012273:desmethylclomipramine; D015283:Citalopram; D019389:Cytochrome P-450 CYP2D6; D002997:Clomipramine