Table 2. [2016 CPIC Dosing recommendations for tricyclic antidepressants based on CYP2D6 phenotype]. - Medical Genetics Summaries

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Table 2.

2016 CPIC Dosing recommendations for tricyclic antidepressants based on CYP2D6 phenotype

Phenotype	Implication	Therapeutic recommendation
CYP2D6 ultrarapid metabolizer	Increased metabolism of TCAs to less active compounds compared to normal metabolizers	Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6
CYP2D6 ultrarapid metabolizer	Lower plasma concentrations of active drugs will increase probability of pharmacotherapy failure	If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers)^a. Utilize therapeutic drug monitoring to guide dose adjustments.
CYP2D6 normal metabolizer	Normal metabolism of TCAs	Initiate therapy with recommended starting dose^b.
CYP2D6 intermediate metabolizer	Reduced metabolism of TCAs to less active compounds compared to normal metabolizers	Consider a 25% reduction of recommended starting dose^b. Utilize therapeutic drug monitoring to guide dose adjustments^a.
CYP2D6 intermediate metabolizer	Higher plasma concentrations of active drug will increase the probability of side effects
CYP2D6 poor metabolizer	Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers	Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6
CYP2D6 poor metabolizer	Higher plasma concentrations will increase the probability of side effects	If a TCA is warranted, consider a 50% reduction of recommended starting dose^b. Utilize therapeutic drug monitoring to guide dose adjustments^a.

: TCAs: Tricyclic Antidepressants
: Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression.
: The therapeutic recommendations for amitriptyline are classified as “moderate” for intermediate CYP2D6 metabolizers and “strong” for ultrarapid, normal, and poor CYP2D6 metabolizers.
^a: Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.
^b: Patients may receive an initial low dose of tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose.
: Table has been adapted from Hicks J.K., Sangkuhl K., Swen J.J., Ellingrod V.L., Müller D.J., Shimoda K., Bishop J.R., Kharasch E.D., Skaar T.C., Gaedigk A., Dunnenberger H.M., Klein T.E., Caudle K.E. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update. Clinical pharmacology and therapeutics. 2016 Dec 20 [Epub ahead of print] (2).

From: Amitriptyline Therapy and CYP2D6 and CYP2C19 Genotype

Medical Genetics Summaries [Internet].

Pratt VM, Scott SA, Pirmohamed M, et al., editors.

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