Cytochrome P450 2D6 genotype variation and venlafaxine dosage

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.

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.

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).

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.