Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study.
OBJECTIVE
Recent studies have revealed that genetic polymorphisms of cytochrome P(450) 2D6 (CYP2D6) are among the factors that determine the interindividual differences in the metabolism and response to antidepressants. We investigated the relationship between persistent mood disorders and the duplication of the CYP2D6 gene, which encodes an enzyme with increased activity.


METHODS
We screened the prevalence of the CYP2D6 genotypes in 108 patients with persistent mood disorders using long polymerase chain reaction (PCR) and the real-time PCR methods. Clinical correlates with the genotypes were also analyzed.


RESULTS
Among the 108 patients, 81 had failed to respond to antidepressants shown to be metabolized by CYP2D6. Of those 81, 8 had a CYP2D6 gene duplication (9.9%, 95% confidence interval 3.4-16.4%) which was higher than the 0.8-1.0% incidence previously observed in healthy Nordic Caucasians. The worst week scores of the Hamilton Depression Rating Scale were higher in the patients with the duplication compared with those without the duplication ( P=0.026, student's t-test).


CONCLUSIONS
These results suggest that the CYP2D6 gene duplication is a possible factor that influences the development of persistence in patients with mood disorders probably by ultrarapid drug metabolism.
Kawanishi
Chiaki
C
Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, Huddinge University Hospital, 14186 Stockholm, Sweden. chiaki@med.yokohama-cu.ac.jp
Lundgren
Stefan
S
Agren
Hans
H
Bertilsson
Leif
L
D000928:Antidepressive Agents / Q000378:metabolism* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020440:Gene Duplication; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011569:Psychiatric Status Rating Scales
D000928:Antidepressive Agents; D019389:Cytochrome P-450 CYP2D6