How Testing Works for CYP2D6 and CYP2C19 Psychiatric Drug Response
Testing looks for the most common variants in two genes, called CYP2D6 and CYP2C19. Our genes act as the body's instruction manual for making the enzymes we need to process food, medications, and other chemicals that enter our body. We all have genes that don't work in the usual way. This happens because we inherit small variations in our instruction codes that make us unique.
CYP2D6
CYP2C19
Your Metabolizer Status
Test Limitations
CYP2D6
The CYP2D6 gene (or simply 2D6) is a member of the cytochrome P450 drug metabolism gene family. This gene makes the 2D6 enzyme that is involved in metabolizing about one quarter of all currently used drugs, including several antidepressants and antipsychotics. There are at least 70 different variants of the 2D6 gene. Most are too rare to need widespread testing. So, genetic tests usually just look for a group of the most common gene variants.
For more information about the variants and their frequencies in different ethnic groups, see Genetics.
CYP2C19
The CYP2C19 gene (or simply 2C19) is a member of the cytochrome P450 drug metabolism gene family. This gene makes the 2C19 enzyme that is involved in metabolizing about 15% of currently used drugs, including several antidepressants. There are at least 20 different variants of the 2C19 gene, but most of these are also too rare to need widespread testing. Testing for the two most common variants, called 2C19*2 and 2C19*3, finds most people who are poor metabolizers from any ethnic background.
For more information about the variants and their frequencies in different ethnic groups, see Genetics.
Your Metabolizer Status
Every person has two copies of each drug metabolism gene - one from each parent. Your combination of variants places you in a specific category for each gene that is tested:
| Metabolizer Type | Drug Response |
| Extensive Metabolizer (EM) | This is the most common result and is "normal". An EM's genes produce a typical amount of enzyme. EMs usually have normal drug response. |
| Poor Metabolizer (PM) | PMs have gene variations that result in an inactive enzyme or no enzyme at all. PMs have a reduced response or no response and may have increased side effects |
| Ultrarapid Metabolizer (UM) | UMs usually have more than two functional copies of the gene, and they produce a larger-than-normal amount of enzyme. UMs may have a reduced or no response and may have increased side effects |
Test Limitations
Genetic testing looks only at a group of variants that are common enough to be worth testing. This testing can’t find all variants in the CYP2D6 or CYP2C19 genes that could cause someone to be a poor or ultrarapid metabolizer. The result is considered normal (extensive metabolizer) when no variants are found. A normal result doesn’t guarantee that you don’t have a variant and won’t have altered metabolism – but it does make it much less likely.
Also, remember that many different factors influence your response to a drug. There are genes and enzymes other than CYP2D6 and CYP2C19 involved, as well as medical and personal factors.
If you have strong reason to believe that you have altered drug metabolism, a different test is also possible. This test involves giving you a specific dose of a drug that is metabolized by the enzyme in question – called a “probe” drug. Your doctor can then track your urine levels of the drug and/or its components as it is being broken down to figure out how quickly you metabolize the probe drug. This information helps predict your metabolizer status.
