Friday, March 15, 2013

CPIC publishes guidelines for tricyclic antidepressants and CYPs

Guidelines regarding the use of pharmacogenomic tests in dosing for tricyclic antidepressants have been published in Clinical Pharmacology and Therapeutics.  The guideline focuses on amitriptyline and nortriptyline dosing for individuals with CYP2D6 and CYP2C19 haplotypes being treated for depression. Since most studies have examined the effects of CYP2D6 and CYP2C19 haplotypes independently the guideline tables consider these separately. A combined table is provided with the caution that further studies are needed to develop moderate or strong dosing recommendations for tricyclics when considering combined CYP2D6/CYP2C19 phenotypes.

The guideline recommends avoiding amitriptyline use in CYP2D6 and CYP2C19 poor metabolizers and ultrarapid metabolizers, and to consider dose modifications in those with intermediate metabolizer status. 

Other tricyclics for which there is less published clinical data, but which have pharmacokinetic data and follow a similar pattern of metabolism by CYPs are also discussed and the evidence listed in the supplement. These include -->clomipramine, desipramine, doxepin, imipramine and trimipramine.

The relevant papers used to compile the evidence are annotated in PharmGKB under the PGx tabs for each drug, and gene-centered PharmGKB pathways are available for clomipramine, doxepin and imipramine/desipramine (and amitriptyline/nortriptyline pharmacokinetic pathway is coming soon). 

To find out more:

Please click here to see excerpts from the guideline and access downloads of the article and supplement . 

Please click here for a complete list of CPIC publications.