CYP2D6 mutations and therapeutic outcome in schizophrenic patients.
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).


METHODS
Prospective, observational study.


METHODS
Two psychiatric hospitals and a university-affiliated nonpsychiatric hospital.


METHODS
Thirty-nine consecutive schizophrenic patients (POP 1), 89 schizophrenics of French Canadian origin (POP 2), and 384 healthy French Canadians (POP 3).


METHODS
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.


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.


CONCLUSIONS
Common CYP2D6 mutant alleles were not associated with schizophrenia or with disease symptoms, antipsychotic-related adverse effects, or attitudes toward treatment.
Hamelin
B A
BA
Laval Hospital and Faculty of Pharmacy, Laval University, Ste-Foy, Quebec, Ontario, Canada.
Dorson
P G
PG
Pabis
D
D
Still
D
D
Bouchard
R H
RH
Pourcher
E
E
Rail
J
J
Turgeon
J
J
Crismon
M L
ML
D000293:Adolescent; D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D007527:Isoenzymes; D019389:Cytochrome P-450 CYP2D6