Antipsychotic drug-induced movement disorders in schizophrenics in relation to CYP2D6 genotype.
BACKGROUND
Approximately 5-10% of Caucasians (poor metabolisers) show impaired metabolism of at least 20 therapeutically important drugs, including a number of commonly used antipsychotic agents, because they lack the cytochrome p450 enzyme CYP2D6. The molecular basis of this defect is now well understood and simple genotyping tests using the polymerase chain reaction (PCR) have been developed.


METHODS
To determine whether poor metabolisers are more susceptible to acute dystonic reactions and chronic movement disorders associated with the administration of antipsychotic drugs, we determined CYP2D6 genotypes in a group of 76 schizophrenics using previously described methods involving PCR and restriction fragment length polymorphism analysis.


RESULTS
There was no difference in genotype frequencies between the schizophrenics and a normal control population, suggesting that CYP2D6 genotype was not a factor in determining susceptibility to the disease. However, four of the five poor metabolisers compared with 44% of the remaining subjects were suffering from a movement disorder at the time of the study, although because of the small number of poor metabolisers in the group the difference was not statistically significant. Poor metabolisers were not more likely to suffer an acute dystonic reaction.


CONCLUSIONS
CYP2D6 genotype is not a determinant of susceptibility to acute dystonic reactions but may be a contributory factor in antipsychotic drug-induced movement disorders including tardive dyskinesia.
Armstrong
M
M
Department of Pharmacological Sciences, University of Newcastle upon Tyne.
Daly
A K
AK
Blennerhassett
R
R
Ferrier
N
N
Idle
J R
JR
D014150:Antipsychotic Agents / Q000009:adverse effects*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D004421:Dystonia / Q000139:chemically induced; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6