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CYP2D6 Mutations and Therapeutic Outcome in Schizophrenic Patients
Author(s) -
Hamelin Bettina A.,
Dorson Peter G.,
Pabis Dennis,
Still Daniel,
Bouchard RochH.,
Pourcher Emmanuel,
Rail Jimmy,
Turgeon Jacques,
Crismon M. Lynn
Publication year - 1999
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.19.13.1057.31593
Subject(s) - cyp2d6 , genotype , medicine , antipsychotic , allele , observational study , psychiatry , adverse effect , schizophrenia (object oriented programming) , genetics , biology , cytochrome p450 , gene , metabolism
Study Objective. To investigate whether a relationship exists between the most common known cytochrome P450 (CYP) isozyme 2D6 mutations and schizophrenia. Because most antipsychotic and antidepressant agents interact with CYP2D6, we also investigated clinical outcomes in schizophrenic poor metabolizers (PMs) and extensive metabolizers (EMs). Design. Prospective, observational study. Setting. Two psychiatric hospitals and a university‐affiliated nonpsychiatric hospital. Subjects. Thirty‐nine consecutive schizophrenic patients (POP 1), 89 schizophrenics of French Canadian origin (POP 2), and 384 healthy French Canadians (POP 3). Intervention. All study subjects were genotyped for CYP2D6 mutant alleles. POP 1 patients were evaluated before and after 21 or more days of treatment with antipsychotic drugs metabolized at least in part by CYP2D6. Measurements and Main Results. Whole blood was collected to determine CYP2D6 alleles *1, *3, *4, *5, *6, and *7 using standard restriction fragment length polymorphisms and polymerase chain reaction techniques. In comparison, CYP2D6 genotypes were determined in POP 2 and POP 3. Twenty‐three (59.0%) of 39 patients in POP 1 were genotypically EM homozygotes, 15 (38.4%) were EM heterozygotes, and 1 (2.6%) was a PM. Similar genotype distributions were determined in POP 2 and in POP 3. Genotype distributions for all three populations were in Hardy‐Weinberg equilibrium (p>0.05), and there was no significant difference among them (p=0.857). In POP 1, no differences were seen among genotypes in disease symptom severity, number and severity of adverse drug effects, or attitudes toward drug treatment at baseline and at the end of the study. In fact, all patients improved significantly during their hospital stay (all p<0.05), although independent of the CYP2D6 genotype. Conclusion. Common CYP2D6 mutant alleles were not associated with schizophrenia or with disease symptoms, antipsychotic‐related adverse effects, or attitudes toward treatment.