Understanding the Gene-Drug Interaction Chart

You’ve taken the GeneSight® test and have the results in hand. Your healthcare provider has likely reviewed the results pages with you.

As you review the GeneSight Psychotropic report, you may see a chart called the gene-drug interaction chart. This chart provides information about which pharmacokinetic genes are involved in metabolism of each medication included on the report. While the GeneSight test’s algorithm evaluates pharmacodynamic genes in other parts of the report, those are not included in this gene-drug interaction chart.

What are pharmacodynamic and pharmacokinetic genes?

There are two types of genes evaluated by the algorithm of the GeneSight test:

• Pharmacokinetic genes tell us what the body does to medication. These genes provide information on how a patient may break down certain medications.
• Pharmacodynamic genes tell us what the medication does to the body. These genes provide information on likelihood of response and/or risk of side effects for certain medications.

 Why are gene-drug interactions important?

A patient’s genetic variations may impact how they metabolize or respond to certain medications commonly prescribed to treat depression, anxiety, ADHD and other psychiatric conditions. The GeneSight report shows whether there are gene-drug interactions for more than 60 FDA-approved mental health medications.

But why are these gene-drug interactions important? The pharmacokinetic genes that are evaluated on the GeneSight report can tell whether a patient processes some medications too quickly, or others, too slowly. If a pharmacokinetic gene-drug interaction causes a patient to process medication either too fast or too slow, it may cause complications.

Research has found that people fall into one of four general metabolizer types for pharmacokinetic genes:

• Poor Metabolizer: Medication is broken down very slowly. May experience side effects at standard doses.
• Intermediate Metabolizer: Slow rate of metabolism. May have too much medication at standard doses, potentially causing side effects.
• Extensive (Normal) Metabolizer: Normal rate of metabolism. Has normal amount of medication at standard doses.
• Ultrarapid Metabolizer: Medication is rapidly broken down. Medication may be removed from a patient’s system too quickly to provide symptom relief.

Can you explain the format of the gene-drug interaction chart?

The gene-drug interaction chart provides additional information about which pharmacokinetic genes are involved in the metabolism of each medication on the report. Listed across the top of the chart are the pharmacokinetic genes included on the GeneSight test, and medications are listed in a column on the left side.

There are dots (either shaded, unshaded, or half-shaded) on the chart. Any dot means that the gene is involved in the metabolism of the associated medication.

• A shaded dot – a variation was found in the patient’s genotype that may impact medication metabolism.
• An unshaded dot – the gene is associated with medication metabolism, but the patient’s predicted phenotype is normal and shouldn’t impact medication metabolism.
• Half-shaded dot – the phenotype is dependent on smoking status, with smokers being ultrarapid metabolizers.

Why do I see shaded dots for medications in the green category?

If your report has shaded dots in the green “Use as Directed” category, you could have a variation in one or more pharmacokinetic genes, but this variation is unlikely to impact your overall metabolism to that medication. One reason could be that while a gene is involved in the metabolism of the medication, its role is not clinically significant enough to warrant a change in dosing or being moved from the green “use as directed” category. Another reason may be compensation among the other genes known to metabolize the medication, resulting in the medication not being moved from the green “Use as Directed” category.

Questions?

For more about the GeneSight test, please call us at 855.891.9415 or email us at medinfo@genesight.com.

Our articles are for informational purposes only and are reviewed by our Medical Information team, which includes PharmDs, MDs, and PhDs. Do not make any changes to your current medications or dosing without consulting your healthcare provider.

The GeneSight test must be ordered by and used only in consultation with a healthcare provider who can prescribe medications. As with all genetic tests, the GeneSight test results have limitations and do not constitute medical advice. The test results are designed to be just one part of a larger, complete patient assessment, which would include proper diagnosis and consideration of your medical history, other medications you may be taking, your family history, and other factors.