Normal CYP2C19 enzyme activity.
Important Instructions: Please use CYP2D6 Activity Score to select the appropriate recommendation below.
CYP2D6 Ultrarapid Metabolizer (Activity Score >2.25)
Increased CYP2D6 enzyme activity.
Clinical Implications
- Increased risk of treatment failure with paroxetine and vortioxetine. Normal response expected with escitalopram, citalopram, and sertraline.
Therapeutic Recommendation
- Avoid vortioxetine and paroxetine. OR
- If vortioxetine use is warranted increasing the target maintenance dose by 50% or more may be needed for efficacy.
AND
- Consider CYP2C19 SSRI’s (e.g., escitalopram, citalopram, and sertraline*) as alternative because of patient’s CYP2C19 metabolizer status. OR
- Consider fluoxetine or non-SSRI antidepressant (e.g., duloxetine, bupropion, venlafaxine).
*Lower doses and slower titrations may be warranted depending on CYP2B6 phenotype, which was not tested for.
CYP2D6 Normal – Ultrarapid Metabolizer (Activity Score 1.5+, or 2+)**
Normal to increased CYP2D6 enzyme activity.
Clinical Implications
- Possible increased risk of treatment failure with paroxetine and vortioxetine. Normal response expected with escitalopram, citalopram, and sertraline.
Therapeutic Recommendation
- Avoid vortioxetine and paroxetine. OR
- If vortioxetine use is warranted increasing the target maintenance dose by 50% or more may be needed for efficacy.
AND
- Consider CYP2C19 SSRI’s (e.g., escitalopram, citalopram, and sertraline*) as alternative because of patient’s CYP2C19 metabolizer status. OR
- Consider fluoxetine or non-SSRI antidepressant (e.g., duloxetine, bupropion, venlafaxine).
*Lower doses and slower titrations may be warranted depending on CYP2B6 phenotype, which was not tested for.
CYP2D6 Normal Metabolizer (Activity Score of 1.25-2.25)**
Normal CYP2D6 enzyme activity.
Clinical Implications
- Normal response expected with paroxetine, fluvoxamine, vortioxetin, venlafaxine, escitalopram, citalopram, and sertraline.
Therapeutic Recommendation
- Use these SSRIs*, vortioxetine, and venlafaxine at standard doses.
*Lower doses and slower titrations may be warranted for sertraline depending on CYP2B6 phenotype, which was not tested for.
CYP2D6 Intermediate Ultrarapid Metabolizer (Activity Score 0.25+, 0.5+, 0.75+, or 1+)**
Possible increased, normal, or decreased CYP2D6 enzyme activity. Exact activity cannot be determine because gene duplication and assay limitations.
Clinical Implications
- Possible increased risk of treatment failure with paroxetine and vortioxetine OR possible increased risk of adverse effects/events (e.g., insomnia, GI dysfunction, sexual dysfunction, arrythmias) with paroxetine and fluvoxamine. Normal response expected with escitalopram, citalopram, and sertraline.
Therapeutic Recommendation
- Avoid vortioxetine and paroxetine. OR
- If vortioxetine use is warranted increasing the target maintenance dose by 50% or more may be needed for efficacy.
AND
- Consider CYP2C19 SSRI’s (e.g., escitalopram, citalopram, and sertraline*) as alternative because of patient’s CYP2C19 metabolizer status. OR
- Consider fluoxetine or non-SSRI antidepressant (e.g., duloxetine, bupropion, venlafaxine).
*Lower doses and slower titrations may be warranted depending on CYP2B6 phenotype, which was not tested for.
CYP2D6 Intermediate Metabolizer (Activity Score 0.25-1)**
Decreased CYP2D6 enzyme activity.
Clinical Implications
- Potential for increased risk of adverse effects/events (e.g., insomnia, GI dysfunction, sexual dysfunction, arrythmias) with paroxetine, vortioxetine, and fluvoxamine. Normal response expected with escitalopram, citalopram, and sertraline.
Therapeutic Recommendation
- Use these SSRIs*, vortioxetine, and venlafaxine at standard doses. AND
- Consider a lower starting dose and slower titration if using paroxetine.
*Lower doses and slower titrations may be warranted depending on CYP2B6 phenotype, which was not tested for.
CYP2D6 Poor Metabolizer (Activity Score 0)
No CYP2D6 enzyme activity.
Clinical Implications
- Increased risk of adverse effects/events (e.g., insomnia, GI dysfunction, sexual dysfunction, arrythmias) with paroxetine, fluvoxamine, vortioxetine, and venlafaxine. Normal response expected with escitalopram, citalopram, and sertraline.
Therapeutic Recommendation
- Avoid paroxetine, fluvoxamine, and venlafaxine OR decrease dose by 50% if use is warranted. AND
- Avoid vortioxetine OR utilize with a maximum dose of 10 mg/day.
AND
- Consider CYP2C19 SSRI’s (e.g., sertraline*, escitalopram, or citalopram) as alternative because of patient’s CYP2C19 metabolizer status. OR
- Consider fluoxetine or non-SSRI antidepressant (e.g., duloxetine, bupropion, desvenlafaxine).
*Lower doses and slower titrations may be warranted depending on CYP2B6 phenotype, which was not tested for.
**Previously some labs have designated an Activity Score of 1 as Normal Metabolizers.