Dr. Oesterheld's comment: This study supports the value of genetic CYP2D6 testing when a patient on venlafaxine has difficulty tolerating a low dose (75Mg) of the drug.

Mayo Clin Proc. 2007 Sep;82(9):1065-8.
Cytochrome P450 2D6 genotype variation and venlafaxine dosage.
McAlpine DE, O'Kane DJ, Black JL, Mrazek DA.

Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. mcalpine.donald@mayo.edu

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.

PATIENTS AND 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).

CONCLUSION

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.

PMID: 17803873