Effects of CYP2D6 polymorphisms on neuroleptic malignant syndrome.
OBJECTIVE
Neuroleptic malignant syndrome (NMS) is one of the most serious adverse reactions to antipsychotic medications. We accumulated data on Japanese NMS patients and, in a study designed to examine the effects of drug metabolism on the occurrence of NMS, tested the possibility of association between NMS and CYP2D6 polymorphisms.


METHODS
We studied 53 patients who had experienced NMS and 112 healthy individuals. We determined what drugs the patients with NMS had been given and retrospectively identified candidates for drugs causing NMS. We screened the prevalence of CYP2D6 genotypes using polymerase chain reaction and restriction fragment length polymorphism analyses.


RESULTS
The prevalence of *5 alleles in the group of all patients with NMS was higher than that in the controls, though this difference was not statistically significant (10.4% vs. 5.4%; P = 0.107; odds ratio (OR) 2.05; 95% confidence interval (CI) 0.87-4.80). No association was found between the frequency of *10 alleles and the occurrence of NMS. We found *4 and duplicated alleles in only one patient each among the patients with NMS. A total of 29 patients appeared to have developed NMS as a result of having taking CYP2D6 substrates. The prevalence of *5 alleles in these 29 patient was significantly higher than that in the controls (15.5% vs. 5.4%; P = 0.020; OR 3.25; 95% CI 1.30-8.13).


CONCLUSIONS
Our findings suggest that the CYP2D6*5 allele is likely to affect vulnerability to development of NMS.
Kato
Daiji
D
Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
Kawanishi
Chiaki
C
Kishida
Ikuko
I
Furuno
Taku
T
Suzuki
Kyoko
K
Onishi
Hideki
H
Hirayasu
Yoshio
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009459:Neuroleptic Malignant Syndrome / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6
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