Increased 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, vortioxetine, escitalopram, citalopram, and possibly 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 fluoxetine, sertraline*, or non-SSRI antidepressant (e.g., venlafaxine, duloxetine, bupropion, or others). OR
- Consider escitalopram or citalopram titrated to a higher overall maintenance dose.
*Higher maintenance doses 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
- Increased risk of treatment failure with escitalopram, citalopram, and possibly sertraline, paroxetine, and vortioxetine
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 fluoxetine, sertraline*, or non-SSRI antidepressant (e.g., venlafaxine, duloxetine, bupropion, or others). OR
- Consider escitalopram or citalopram titrated to a higher overall maintenance dose.
*Higher maintenance doses 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, vortioxetine, and venlafaxine. Increased risk of treatment failure with escitalopram, citalopram, and possibly sertraline.
Therapeutic Recommendation
- Consider escitalopram escitalopram or citalopram titrated to a higher overall maintenance dose.
OR
- Consider sertraline* or non-CYP2C19 SSRI (i.e., paroxetine, fluoxetine, or fluvoxamine) as alternative because of patient’s CYP2D6 metabolizer status.
OR
- Consider non-SSRI antidepressant (e.g., duloxetine, bupropion, venlafaxine, vortioxetine).
*Higher maintenance doses may be warranted 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
- Increased risk of treatment failure with escitalopram, citalopram and possibly sertraline, paroxetine, and vortioxetine OR possible increased risk of adverse effects/events (e.g., insomnia, GI dysfunction, sexual dysfunction, arrythmias) with paroxetine and fluvoxamine.
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 fluoxetine, sertraline*, or non-SSRI antidepressant (e.g., venlafaxine, duloxetine, bupropion, or others). OR
- Consider escitalopram or citalopram titrated to a higher overall maintenance dose.
*Higher maintenance doses 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. Increased risk of treatment failure with escitalopram, citalopram, and possibly sertraline.
Therapeutic Recommendation
- Consider escitalopram or citalopram titrated to a higher overall maintenance dose.
OR
- Consider sertraline* or non-CYP2C19 SSRI (i.e., paroxetine, fluoxetine, or fluvoxamine) as alternative because of patient’s CYP2D6 metabolizer status. AND
- Consider a lower starting dose and slower titration if using paroxetine.
OR
- Consider non-SSRI antidepressant (e.g., duloxetine, bupropion, venlafaxine).
*Higher maintenance doses 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. Increased risk of treatment failure with escitalopram, citalopram, and possibly 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 escitalopram or citalopram titrated to a higher overall maintenance dose. OR
- Consider sertraline* or non-SSRI antidepressant (e.g., desvenlafaxine, duloxetine, bupropion, or others).
*Higher maintenance doses 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.