CYP2D6, CYP2C19 and SSRIs (Fluvoxamine, Paroxetine, Citalopram, Escitalopram, Sertraline), Vortioxetine, Venlafaxine: CYP2C19 Poor Metabolizer

No 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. Increased risk of adverse effects/events (e.g., insomnia, GI dysfunction, sexual dysfunction, arrythmias) with escitalopram, citalopram, and sertraline.

Therapeutic Recommendation

  • Avoid sertraline*, escitalopram, and citalopram OR decrease dose by 50% and use slow titrations if use is warranted.

AND

  • Aoid 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 or non-SSRI antidepressant (e.g., venlafaxine, duloxetine, bupropion, or others).

*Response to sertraline is also impacted by CYP2B6 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. Increased risk of adverse effects/events (e.g., insomnia, GI dysfunction, sexual dysfunction, arrythmias) with escitalopram, citalopram, and sertraline.

Therapeutic Recommendation

  • Avoid sertraline*, escitalopram, and citalopram OR decrease dose by 50% and use slow titrations if use is warranted.

AND

  • 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 or non-SSRI antidepressant (e.g., venlafaxine, duloxetine, bupropion, or others).

*Response to sertraline is also impacted by CYP2B6 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 adverse effects/events (e.g., insomnia, GI dysfunction, sexual dysfunction, arrythmias) with escitalopram, citalopram, and sertraline.

Therapeutic Recommendation

  • Avoid sertraline*, escitalopram, and citalopram OR decrease dose by 50% if use is warranted.

AND

  • Consider 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).

*Response to sertraline is also impacted by CYP2B6 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. 
  • Increased risk of adverse effects/events (e.g., insomnia, GI dysfunction, sexual dysfunction, arrythmias) with escitalopram, citalopram, and sertraline.

Therapeutic Recommendation

  • Avoid sertraline*, escitalopram, and citalopram OR decrease dose by 50% and use slow titrations if use is warranted.

AND

  • 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 or non-SSRI antidepressant (e.g., venlafaxine, duloxetine, bupropion, or others).

*Response to sertraline is also impacted by CYP2B6 which was not tested for.

CYP2D6 Intermediate Metabolizer (Activity Score 0.25-1)**

Decreased CYP2D6 enzyme activity.

Clinical Implications

  • Potential for increased risk with paroxetine, vortioxetine, and fluvoxamine AND increased risk with escitalopram, citalopram, and sertraline of adverse effects/events (e.g., insomnia, GI dysfunction, sexual dysfunction, arrythmias).

Therapeutic Recommendation

  • Avoid sertraline*, escitalopram, and citalopram OR decrease dose by 50% if use is warranted.

AND

  • Consider 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).

*Response to sertraline is also impacted by CYP2B6 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, venlafaxine, escitalopram, citalopram, and sertraline.

Therapeutic Recommendation

  • Avoid sertraline*, escitalopram, citalopram, paroxetine, fluvoxamine, and venlafaxine OR decrease dose by 50% if use is warranted. AND
  • Avoid vortioxetine OR utilize with a maximum dose of 10mg/day.

AND

  • Consider non-SSRI antidepressant (e.g., desvenlafaxine, duloxetine, bupropion, or others).

*Response to sertraline is also impacted by CYP2B6 which was not tested for.

**Previously some labs have designated an Activity Score of 1 as Normal Metabolizers.

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