CYP2D6 genotype and antipsychotic-induced extrapyramidal side effects in schizophrenic patients.
OBJECTIVE
In order to evaluate whether poor metabolizers (PM) of debrisoquine are overrepresented among patients with acute dystonic reactions and chronic movement disorders associated with the administration of antipsychotic drugs, the CYP2D6 genotype was determined in schizophrenic patients.


METHODS
Allele status for CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*6 as well as gene duplication was determined by allele-specific PCR, long-PCR and restriction fragment length polymorphism analysis (RFLP) in 119 schizophrenic patients (99 males and 20 females). All subjects were treated with antipsychotics metabolized, at least partially, by this isozyme. Sixty-three of the patients (52.9%) had a history of extrapyramidal side effects (EPS), while 56 (47.1%) had not experienced such problems (controls).


RESULTS
Sixty-five patients (54.6%) were homozygous for a functional CYP2D6*1 allele, 44 (37.0%) were heterozygous for detrimental alleles, and 4 (3.4%), who carried two detrimental alleles, were classified as PM. In six patients (5.0%) duplication of a functional CYP2D6 gene was found, and they were consequently classified as ultrarapid metabolizers (UM). Homo- and heterozygous extensive metabolizers (EM) as well as UM were equally distributed between patients with and without EPS, whereas all the PM had a history of EPS. No significant differences in allele frequencies between the two groups were found.


CONCLUSIONS
Although the results cannot be considered conclusive due to the small number of PM patients in our study, the PM genotype may be a predisposing factor for antipsychotic-induced EPS. Knowledge of the CYP2D6 genotype, before starting antipsychotic therapy, might be useful in identifying subjects at risk of developing EPS.
Scordo
M G
MG
Department of Medical Laboratory Sciences and Technology, Karolinska Institutet, Huddinge University Hospital, Sweden. gabriella-s@usa.net
Spina
E
E
Romeo
P
P
Dahl
M L
ML
Bertilsson
L
L
Johansson
I
I
Sjöqvist
F
F
D000328:Adult; D000368:Aged; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001480:Basal Ganglia Diseases / Q000139:chemically induced*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics*
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6