citalopram
Clinical implication
Greatly reduced metabolism when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects.
Guideline overview
CPIC® guideline recommends considering a reduced starting dose or an alternative medication not predominantly metabolized by CYP2C19. CPIC rates this recommendation as “moderate” in strength.
See full CPIC® guideline at PharmGKB.
FDA-approved label (Celexa®) notes that the maximum recommended dose is lower for CYP2C19 poor metabolizers due to the risk of QT prolongation, but please see complete label for full details.
NOTE: Paroxetine, fluvoxamine, and fluoxetine are three SSRI medications not predominantly metabolized by CYP2C19. For more information please see the CPIC® guideline recommendations for paroxetine and fluvoxamine at PharmGKB.
doxepin and other tertiary amine tricyclic antidepressants: amitriptyline, clomipramine, imipramine, and trimipramine
Clinical implication
Greatly reduced metabolism compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.
Guideline overview
CPIC® guideline recommends avoiding tertiary amine use and considering an alternative drug not predominantly metabolized by CYP2C19. If a tertiary amine is warranted, CPIC® recommends considering a reduced starting dose and utilizing therapeutic drug monitoring to guide dose adjustments. These recommendations only apply to higher initial doses of tricyclic antidepressants (TCAs) for treatment of conditions such as depression and are rated as “moderate” in strength for amitriptyline and “optional” for doxepin and other tertiary amine TCAs.
See full CPIC® guideline at PharmGKB.
NOTE: Tricyclic antidepressants (both tertiary and secondary) are also metabolized by the CYP2D6 enzyme, and the CPIC® guideline for TCAs includes dosing recommendations based on CYP2D6 genotype. To determine a patient’s complete pharmacogenetic profile for TCA prescribing, CYP2D6 genotyping may be appropriate. The 23andMe test does not currently include CYP2D6 genotyping.
escitalopram
Clinical implication
Greatly reduced metabolism when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects.
Guideline overview
CPIC® guideline recommends considering a reduced starting dose or an alternative drug not predominantly metabolized by CYP2C19. CPIC rates this recommendation as “moderate” in strength.
See full CPIC® guideline at PharmGKB.
NOTE: Paroxetine, fluvoxamine, and fluoxetine are three SSRI medications not predominantly metabolized by CYP2C19. For more information please see the CPIC® guideline recommendations for paroxetine and fluvoxamine at PharmGKB.
sertraline
Clinical implication
Greatly reduced metabolism when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects.
Guideline overview
CPIC® guideline includes an optional recommendation to consider a reduced starting dose or an alternative drug not predominantly metabolized by CYP2C19.
See full CPIC® guideline at PharmGKB.
NOTE: Paroxetine, fluvoxamine, and fluoxetine are three SSRI medications not predominantly metabolized by CYP2C19. For more information please see the CPIC® guideline recommendations for paroxetine and fluvoxamine at PharmGKB.