Citalopram and escitalopram are metabolized by the liver to inactive metabolites. The protein in the liver responsible for the majority of this metabolism is the cytochrome p450 enzyme CYP2C19 (pronounced "sip two see nineteen").  

Across populations, CYP2C19 protein alleles can have different genetic variants that impact its ability to metabolize citalopram and escitalopram. The different alleles can produce five different metabolism phenotypes: ultrarapid, rapid, normal, intermediate and poor metabolism. Of these, the ultrarapid and rapid metabolism phenotypes have been shown to have lower drug levels, so higher doses may be needed to achieve clinical efficacy. The poor metabolism phenotype has been shown to increase the risk of side effects and toxicity due to higher drug levels so a lower starting dose should be considered.

Sertraline is metabolized by the liver to inactive metabolites. The protein in the liver responsible for the majority of this metabolism is the cytochrome p450 enzyme CYP2C19 (pronounced "sip two see nineteen").  

Across populations, CYP2C19 protein alleles can have different genetic variants that impact its ability to metabolize sertraline. The different alleles can produce five different metabolism phenotypes: ultrarapid, rapid, normal, intermediate, and poor metabolism. The poor and intermediate metabolism phenotypes have been shown to increase the risk of side effects and toxicity due to higher drug levels so a lower starting dose should be considered.

Paroxetine and vortioxetine are metabolized by the liver to inactive metabolites. The protein in the liver responsible for the majority of this metabolism is the cytochrome p450 enzyme CYP2D6 (pronounced "sip two dee six").  

Across populations, CYP2D6 protein alleles can have different genetic variants that impact their ability to metabolize paroxetine, vortioxetine, and other medications. The different alleles can produce four different metabolism phenotypes: ultrarapid, normal, intermediate, and poor metabolizers. The ultrarapid metabolism phenotype has been shown to increase paroxetine metabolism, leading to a risk of therapeutic failure. The poor metabolism phenotype has been shown to decrease both paroxetine and vortioxetine metabolism, resulting in increased drug levels and a higher risk of side effects.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) is a group who evaluates the evidence for the use of pharmacogenetics and then develops clinical practice guidelines. For the SSRIs, extensive guideline information can be found at https://cpicpgx.org/guidelines/cpic-guideline-for-ssri-and-snri-antidepressants/ a reference maintained by CPIC.

At UCHealth the use of pharmacogenetics when prescribing certain SSRIs will occur in patients who meet the following conditions:
1) Provided a blood or saliva sample to the CCPM biobank, consented for the return of their results, and this sample has undergone genotyping OR the patient is being seen in a clinic which is currently using pharmacogenetic testing as part of standard care (e.g., the UCHealth GI Oncology Clinic).  
2) Are prescribed citalopram, escitalopram, paroxetine, sertraline, or vortioxetine.

For patients enrolled in the biobank, this process takes a minimum of 4-6 weeks but may take several years. Therefore, results will not be available at initial presentation if a patient has not previously enrolled in the biobank.

For citalopram and escitalopram: 

If you are a provider AND your patient is a CYP2C19 poor, rapid, or ultrarapid metabolizer, an inline medication warning will appear if you attempt to prescribe or refill citalopram or escitalopram in UCHealth's EHR. 

For sertraline:

If you are a provider AND your patient is a CYP2C19 poor or intermediate metabolizer, an inline medication warning will appear if you attempt to prescribe or refill citalopram or escitalopram in UCHealth's EHR. 

For paroxetine & vortioxetine:

If you are a provider AND your patient is a CYP2D6 ultrarapid (paroxetine only) or poor metabolizer (both paroxetine and vortioxetine), an inline medication warning will appear if you attempt to prescribe or refill paroxetine or vortioxetine in UCHealth's EHR. 

If these inline medication warnings are visible, links to resources will be listed for your reference. There is patient education text available for UCHealth providers to use in discharge paperwork or the after visit summary (AVS).