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2. Genotype Influences Medication Blood Levels: Fluoxetine, Paroxetine,
and (Es)citalopram
Simon Kung, M.D.
Associate Professor of Psychiatry
Mayo Clinic

3. The Clinical Pharmacogenetics Implementation Consortium: SSRIs and 2D6
Enzyme
Major Findings
Level of Evidence
Fluoxetine
2D6
2D6 poor metabolizers had significantly higher fluoxetine plasma levels compared to extensive metabolizers. 
High
Hicks, J. K., Bishop, J. R., Sangkuhl, K., Müller, D. J., Ji, Y., Leckband, S. G., ... & Skaar, T. C. (2015). Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clinical Pharmacology & Therapeutics, 98(2),

4. The Clinical Pharmacogenetics Implementation Consortium: SSRIs and 2D6
Enzyme
Major Findings
Level of Evidence
Paroxetine
2D6
Ultrarapid metabolizers had significantly lower paroxetine plasma levels compared to extensive metabolizers.
High
Hicks, J. K., Bishop, J. R., Sangkuhl, K., Müller, D. J., Ji, Y., Leckband, S. G., ... & Skaar, T. C. (2015). Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clinical Pharmacology & Therapeutics, 98(2),

5. The Clinical Pharmacogenetics Implementation
Consortium
Major Findings
Level of Evidence
2C19 poor metabolizers had significantly higher citalopram/escitalopram plasma levels when compared to the concentrations of all study participants.
High
SSRI
(Es) citalopram
Enzyme
2D6
2C19
Hicks, J. K., Bishop, J. R., Sangkuhl, K., Müller, D. J., Ji, Y., Leckband, S. G., ... & Skaar, T. C. (2015). Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clinical Pharmacology & Therapeutics, 98(2),

6. Key Points
The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides review articles and clinical recommendations about genotype-guided dose adjustments. 
The CPIC also provides literature-review evidence to support their recommendations.
Polymorphisms can result in slower or faster enzyme activity.

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