Abstract | OBJECTIVE: METHOD: Adult inpatients and outpatients were recruited from July 2000 to March 2003 including (1) 325 who were stabilized on risperidone therapy and classified as either expressing moderate-to-marked ADRs (22%, 73/325) or not (78%, 252/325) and (2) 212 who discontinued risperidone and were classified as discontinued due to ADRs (38%, 81/212) or for other reasons (62%, 131/212). Genetic tests were performed by allele-specific polymerase chain reaction and/or by the AmpliChip CYP450 microarray system for up to 34 separate CYP2D6 alleles. Two logistic regression models with dependent variables (moderate-to-marked ADRs while taking risperidone and risperidone discontinuation due to ADRs) were evaluated with respect to the CYP2D6 phenotype. RESULTS: The odds ratios ( ORs) and 95% confidence intervals (CIs) for the CYP2D6 poor metabolizer phenotype in the univariate analyses and after correcting for clinical variables were (1) OR = 3.1 (CI = 1.4 to 7.0) and 3.4 (CI = 1.5 to 8.0) for moderate-to-marked ADRs on risperidone and (2) OR = 3.0 (CI = 0.85 to 10.6) and 6.0 (CI = 1.4 to 25.4) for discontinuation due to ADRs. CONCLUSIONS: The CYP2D6 poor metabolizer phenotype appears to be associated with risperidone ADRs and discontinuation due to ADRs; however, this finding requires further study in larger patient populations. The CYP3A5 and p-glycoprotein exon 21 and 26 genotypes were not significantly associated with risperidone response.
|
Authors | Jose de Leon, Margaret T Susce, Run-Mei Pan, Maureen Fairchild, Walter H Koch, Peter J Wedlund |
Journal | The Journal of clinical psychiatry
(J Clin Psychiatry)
Vol. 66
Issue 1
Pg. 15-27
(Jan 2005)
ISSN: 0160-6689 [Print] United States |
PMID | 15669884
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antipsychotic Agents
- Cytochrome P-450 CYP2D6
- Risperidone
|
Topics |
- Adult
- Antipsychotic Agents
(adverse effects, pharmacokinetics, therapeutic use)
- Basal Ganglia Diseases
(chemically induced, genetics)
- Cytochrome P-450 CYP2D6
(genetics, metabolism, therapeutic use)
- Dose-Response Relationship, Drug
- Drug Therapy, Combination
- Female
- Genetic Variation
- Genotype
- Humans
- Logistic Models
- Male
- Mental Disorders
(drug therapy, genetics, metabolism)
- Oligonucleotide Array Sequence Analysis
- Patient Dropouts
- Pharmacogenetics
- Phenotype
- Polymerase Chain Reaction
- Risperidone
(adverse effects, pharmacokinetics)
- Schizophrenia
(drug therapy, genetics, metabolism)
|