One of the most frequently asked questions from our patients is how to interpret the GeneSight report. The pharmacogenomic report contains a lot of useful, yet complex, information that may be difficult to understand without a medical background.
The most prominent feature of the report is the color-coded categories of medications, bucketed based on an individual’s unique genetic make-up. These categories define the likelihood with which medications may be more or less likely to work for a patient, and which may require dose adjustments or cause an increased risk of side effects based on a patient’s genetic makeup.
A quick interpretation of the four categories are:
Use as Directed
Moderate Gene-Drug Interaction
Significant Gene-Drug Interaction
No Proven Genetic Markers
While the color coding provides an easy-to-digest, quick-to-interpret guide, there’s more to the report than just these categories.
“We often use a stoplight analogy when talking with healthcare providers and patients,” says Holly Johnson, Ph.D., medical information manager, Myriad Neuroscience.
She explains:
“Think of an intersection with a stoplight as the point of medication decision making. You can go in any number of directions.
If the light is green, you can pass through the intersection as you would normally drive. Likewise, with the GeneSight test, when medications fall in the green ‘Use as Directed’ category, it means that there are no genetic variations in the tested genes that predict any abnormal response. However, going back to the intersection analogy, there can be other factors that could cause problems, such as other cars or debris on the road. Similarly, there can be other factors that impact your ability to respond to the medications listed in the green category, such as drug/drug interactions, food/drug interactions, allergies and other factors.
The yellow ‘Moderate Gene-Drug Interaction’ category is like a yellow light – the healthcare provider should slow down and be more thoughtful about how that medication is used. Dosage adjustments, closer monitoring, or other strategies may be necessary.
Red category medications, or those in the ‘Significant Gene-Drug Interaction’ category, should be treated just like a red light: Stop and proceed with caution. It doesn’t mean you can’t go through the intersection (for example, sometimes it is OK to turn right on red), but the healthcare provider needs to carefully consider the information that is being presented.”
Understanding Clinical Considerations
As the analogy suggests, considering other information in addition to the genetic results is important. On the GeneSight report, additional insights in the yellow and red categories come in the form of “Clinical Considerations.”
Click here to view a GeneSight Psychotropic Sample Report.
Clinical considerations are noted in the report with a number on the right-hand side of the medication. These numbers help doctors guide treatment decisions and provide more detailed information about how medications could be impacted by genetic variation. Many healthcare providers use the clinical considerations to help guide discussions with patients about treatment decisions.
Below is a guide to the clinical considerations found on the GeneSight report:
| Clinical Consideration | Explanation |
| 1: Serum level may be too high, lower doses may be required. 2: Serum level may be too low, higher doses may be required. | These considerations reflect an issue with how the medication is metabolized. This may affect how much medication is in an individual’s system and may require a lower or higher dose, respectively. |
| 3: Difficult to predict dose adjustments due to conflicting variations in metabolism. | There is conflicting variation in the genes that metabolize the medication. For example, if there are two genes that affect the medication’s metabolism, and the patient is ultra-rapid for one and poor for the other, it may be difficult to recommend a dose adjustment. |
| 4: Genotype may impact drug mechanism of action and result in reduced efficacy. | These medications are affected by a pharmacodynamic gene, meaning there is an issue with how the medication is able to work on the body. Variation in these genes predicts a reduced response to certain medications. However, pharmacodynamic genes do not affect metabolism, which means that adjusting the dose won’t necessarily improve its effectiveness. |
| 6: Use of this drug may increase risk of side effects. | The patient has an increased risk for side effects when taking this medication. This can be the result of high levels of medication in the system or an effect caused by the drug’s mechanism of action. |
| 7: Smoking status changes the results of this medication. See next section labeled Smokers for smoking results. | This clinical consideration indicates the medication is affected by smoking status and that the results in the following section labeled ‘Smokers’ should be used if the patient smokes. |
| 8: FDA label identifies a potential gene-drug interaction for this medication. | This indicates that the FDA has made a statement in the medication’s package insert that may have pharmacogenomic implications for the patient. |
| 9: Per FDA label, this medication is contraindicated for this genotype. | The FDA has stated a person with this genotype should not take this medication. |
| 10: This medication does not have identified or clinically proven genetic markers which allow it to be categorized. | Genetic markers have not yet been discovered to reliably predict which genes are involved in the metabolism or therapeutic efficacy of these medications. Due to this lack of evidence, we are not currently able to categorize these medications or provide actionable recommendations. |
Clinical Studies Show Improvement in Remission, When Switching from Red Bin Medications
Clinical studies on the GeneSight® Psychotropic test have shown that green and yellow category medications are more likely to work for patients than red category medications.
In fact, the GUIDED Study, the largest ever pharmacogenomics depression trial, showed patients experienced a 50% improvement in remission rates when the GeneSight Psychotropic test guided their treatment compared to unguided treatment as usual. Furthermore, in a sub-analysis of patients who entered the study on a red category medication, there was a 153% improvement in remission when patients were switched to a green or yellow category medication by week 8 compared to those who remained on red category medications.1
While the GeneSight report has proven to be helpful to healthcare providers in guiding treatment, patients may not always respond to medications that fall in their green category. Genetics provides an important piece of the puzzle – but there are other factors that can influence medication response and susceptibility to side effects, including drug-drug interactions, diet, environmental factors, age, etc.
A patient’s GeneSight results can serve as an objective tool that can be used in concert with these other factors to help guide medication selection.
For more information on how the GeneSight test can help you and your physician, visit genesight.com, email us at medinfo@myriad.com, or phone 855.891.9415.
This document is for educational purposes related to pharmacogenomics and personalized medicine only and should not be considered medical advice. The information is based on scientific opinion from industry experts and is intended to provide additional information to healthcare providers. These materials may be changed, improved, or updated without notice. Assurex Health is not responsible for any errors or omissions contained in third party content. We encourage you to contact us for specific scientific advice regarding our GeneSight® tests. You may print a copy of this document for your own personal noncommercial use. You may not copy any part of this document for any other purpose, and you may not modify any part of this document without the permission of Assurex Health. “GeneSight,” “Assurex” and associated logos are registered trademarks of Assurex Health, Inc. © 2019 Assurex Health, Inc. All rights reserved.
References
- Greden, J.F. et al. Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater- blinded, randomized, controlled study. Journal of Psychiatric Research111, 59-67 (2019).