CYP2C19 is an important detox enzyme responsible for clearing approximately 10% of commonly used clinical drugs. High enzyme activity has been associated with depression. Read on to find out more about CYP2C19 function, gene variants, and factors that decrease enzyme activity.
What is CYP2C19?
This enzyme metabolizes:
- Antidepressants: citalopram, escitalopram [3, 4], amitriptyline , and sertraline 
- Proton pump inhibitors: omeprazole 
- Anticonvulsants: mephenytoin 
- Diazepam 
- Methadone 
- Antimalarial proguanil 
- Anticoagulant warfarin 
- Antiplatelet clopidogrel (Plavix) 
- Antifungal voriconazole 
- MDMA (ecstasy) 
This enzyme is found in the liver. However, it is also active in the fetal brain, with a possible role in brain development .
This enzyme participates in converting arachidonic acid to epoxyeicosatrienoic acids (EETs). EETs have beneficial effects on the heart and blood vessels.
Low enzyme activity was associated with heart disease in a study of 162 subjects .
High CYP2C19 activity was associated with depression and smaller hippocampus volume in a study of 1418 volunteers .
A study of 1472 subjects in Sweden showed that people with high enzyme activity (CYP2C191 carriers) were more likely to be diagnosed with depression than those with defective enzyme function (CYP2C192 carriers) .
Among 209 people with depression who had attempted suicide, those with high enzyme activity showed higher suicidality .
Based on the variants they carry, individuals can be categorized as:
- ultrarapid metabolizers (*1 /*17 or *17 /*17)
- extensive metabolizers (*1/*1)
- intermediate metabolizers (*1 /*2, *1 /*3, or *2 /*17)
- poor metabolizers (*2 /*2 or *2 /*3) 
Poor metabolizers have an increased risk of side effects associated with CYP2C19-metabolized drugs like sertraline .
On the other hand, ultrarapid metabolizers have an increased risk of being refractory (resistant) to proton pump inhibitor (PPI) therapy (meta-analysis, 19 studies) .
Plavix (clopidogrel) is less effective in people with this variant. They are at higher risk of developing heart damage (559 subjects) .
Adults with CYP2C19*17 more often have decreased blood voriconazole levels in therapy (70 patients) .
This variant protects against recurrent heart damage. People with this variant have greater therapeutic responsiveness to Plavix (clopidogrel) but they have an increased risk of developing bleeding (meta-analysis, 11 studies) .
The following factors were found to decrease CYP2C9 activity in laboratory or clinical settings. We recommend against taking supplements or making lifestyle changes to affect CYP2C9 activity. Talk to your doctor before making any significant changes to your diet, lifestyle, or supplement regimen.