Document Detail

Antipsychotic-induced extrapyramidal syndromes and cytochrome P450 2D6 genotype: a case-control study.
MedLine Citation:
PMID:  11927839     Owner:  NLM     Status:  MEDLINE    
To study the association between polymorphism of the cytochrome P450 2D6 gene (CYP2D6) and the risk of antipsychotic-induced extrapyramidal syndromes, as measured by the use of antiparkinsonian medication. Data for this case-control study were obtained from a psychiatric hospital where newly admitted patients are routinely screened for several CYP2D6 mutant alleles. Cases were patients prescribed antiparkinsonian medication during oral antipsychotic drug treatment in the period September 1994 to August 2000. They were divided into those using an antipsychotic drug the metabolic elimination of which depends on the activity of the CYP2D6 enzyme ('CYP2D6-dependent') and those using other antipsychotic drugs. We formed a control group of antipsychotic drug users for both case groups using a matching ratio of 3 : 1 (controls : cases). Control patients were matched on whether or not their prescribed antipsychotic drug was CYP2D6-dependent. Odds ratios for patients who were slow metabolizers versus patients who were extensive metabolizers were calculated using conditional logistic regression and were adjusted for age, gender, dose and other potential confounding factors. We identified 77 case patients who were prescribed a CYP2D6-dependent antipsychotic drug and 54 case patients who were prescribed non CYP2D6-dependent antipsychotic drugs. Among the case- and control-patients using a CYP2D6-dependent antipsychotic drug, the poor metabolizers were more than four times more likely to start with antiparkinsonian medication than the extensive metabolizers (odds ratio 4.44; 95% confidence interval 1.11-17.68). An increased risk was not observed for patients using non CYP2D6-dependent antipsychotic drugs (odds ratio 1.20; 95% confidence interval 0.21-6.79). Genetically impaired CYP2D6 activity can increase the risk of antipsychotic-induced extrapyrimidal syndromes. Poor metabolizers should have their antipsychotic drug dosage reduced when the metabolism of the prescribed drug depends on CYP2D6 activity or should receive an antipsychotic drug that is not CYP2D6-dependent.
Igor Schillevoort; Anthonius de Boer; Jan van der Weide; Linda S W Steijns; Raymund A C Roos; Paul A F Jansen; Hubert G M Leufkens
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacogenetics     Volume:  12     ISSN:  0960-314X     ISO Abbreviation:  Pharmacogenetics     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-02     Completed Date:  2002-09-03     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  9211735     Medline TA:  Pharmacogenetics     Country:  England    
Other Details:
Languages:  eng     Pagination:  235-40     Citation Subset:  IM    
Department of Pharmacoepidemiology & Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands.
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MeSH Terms
Antiparkinson Agents / metabolism,  therapeutic use
Antipsychotic Agents / adverse effects*,  metabolism
Basal Ganglia Diseases / chemically induced*,  drug therapy,  enzymology
Case-Control Studies
Cohort Studies
Cytochrome P-450 CYP2D6 / genetics*,  metabolism
Middle Aged
Risk Factors
Reg. No./Substance:
0/Antiparkinson Agents; 0/Antipsychotic Agents; EC P-450 CYP2D6

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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