Cytochrome P450 2D6 genotype variation and venlafaxine dosage.
OBJECTIVE
To determine whether the presence or absence of a fully functioning cytochrome P450 2D6 allele was associated with the dosage of the antidepressant drug venlafaxine in patients who had either adverse effects or absence of a therapeutic response to treatment with the immediate release or extended release form of venlafaxine.


METHODS
We reviewed the electronic medical records of 199 patients enrolled in a previous pharmacogenomic study (June 1, 2002 through April 30, 2004) who had either adverse effects or the absence of a therapeutic response to treatment with psychotropic medications. This review identified 38 patients previously treated with venlafaxine immediate release or extended release and subsequently genotyped for the 2D6 gene with a commercial genotyping assay. Their dosage was examined along with their 2D6 genotype to determine whether the presence or absence of a fully functioning 2D6 allele was associated with their venlafaxine dosage.


RESULTS
Of the 38 patients, 5 had a 2D6 genotype that consisted of 1 inactive allele and 1 allele associated with decreased activity. None of these 5 patients were able to tolerate treatment with more than 75 mg/d of venlafaxine. The remaining 33 patients had at least 1 fully active 2D6 allele, 26 of whom had been able to tolerate treatment with 150 mg/d or more of venlafaxine (P less than .002).


CONCLUSIONS
Genetic variations of the P450 2D6 gene may contribute to patient-specific variation in response to treatment with venlafaxine. Physicians should be alert to the possibility that an adverse reaction may indicate a slow metabolizer and consider genotyping such patients.
McAlpine
Donald E
DE
Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. mcalpine.donald@mayo.edu
O'Kane
Dennis J
DJ
Black
John L
JL
Mrazek
David A
DA
D000293:Adolescent; D000328:Adult; D000483:Alleles; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects; D001008:Anxiety Disorders / Q000188:drug therapy; D003511:Cyclohexanols / Q000008:administration & dosage* / Q000009:adverse effects; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy; D019263:Dysthymic Disorder / Q000188:drug therapy; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D017211:Treatment Failure; D000069470:Venlafaxine Hydrochloride