Do any of these anecdotes feel familiar?

You have been working with a family for many years and thought you had a great relationship but then after offering to start fluoxetine for the teenage daughter’s depression, the family demands that you get the test that will tell you which drug to prescribe. They insist that your choice of fluoxetine, a first line medication for adolescent depression with FDA approval down to the age 8, is not a good choice, and they worry that you are going to be experimenting on their child by prescribing blindly.

or

A family arrives with a colorful print-out for you, showing desvenlafaxine in a green column and fluoxetine and sertraline in red. They tell you that their 10-year-old son has anxiety treated by a psychologist, but they want you to prescribe. However, they insist that you can only prescribe a green medication because only green will work for their child. They are appalled that you want to prescribe sertraline because red means danger.

So here you are, a caring pediatric primary care provider, feeling comfortable prescribing psychiatric medications, and now a whole new minefield awaits you.

First and foremost, it is important to know that the tests are not all they are purported to be. In fact, on November 1, 2018, the FDA released a consumer warning stating: “The FDA is alerting patients and health care providers that claims for many genetic tests to predict a patient’s response to specific medications have not been reviewed by the FDA and may not have the scientific or clinical evidence to support this use for most medications. Changing drug treatment based on the results from such a genetic test could lead to inappropriate treatment decisions and potentially serious health consequences for the patient.” And in April of this year, the FDA sent a warning letter to a specific laboratory for “illegally marketing certain genetic tests that have not been reviewed by the FDA for safety and effectiveness. “

Yet, we cannot dismiss this field all together! On September 3, 2019, the FDA updated its “Table of Pharmacogenomic Biomarkers in Drug Labeling” and the updated labelling includes several psychiatric medications. Thus, some of the medications we prescribe may have specific written suggestions regarding prescribing based on the results of pharmacogenetic testing.

The Basics

What is pharmacogenetic testing? Pharmacogenetics, also known as pharmacogenomics, is the science of examining specific genes to help match those genes with specific types of medicines or dosages. The science is based on there being polymorphisms in DNA that effect how drugs pass through and interact in our body. Pharmacogenetic testing attempts to look at two aspects of DNA polymorphisms, pharmacodynamics and pharmacokinetics. Pharmacokinetics looks at how the medicines are absorbed, distributed, metabolized and excreted. Different pharmacokinetics can lead to different drug levels in someone’s body. Pharmacodynamics looks at how the drug interacts with the drug targets, so may influence how a medication works.

Let’s start with the pharmacokinetics, where there seems to be more data and evidence surrounding the psychiatric medications.

Much of the hype around the testing implies that the testing will determine why your patients are having so many side effects, and there are claims that testing will help you find a medicine that will not cause side effects in your patients. These assertions are overblown. While the tests may help adjust dosages, some adverse drug reactions are due to hypersensitivities and not absorption, while many others are due to concomitant medications, smoking, medical issues, and psychological states. The boxed warning about suicidality remains as much of a warning, whether one has or has not had pharmacogenetic testing and whether the medication is in red or green!

The evidence is even less clear in Pharmacodynamics. The thinking in this area of study is that genetic variations in the drug targets may affect drug outcome. However, much of this data is still theoretical and in its early stages. As the FDA said in 2018, “The relationship between DNA variations and the effectiveness of antidepressant medications has never been established.”

What about outcomes? Again, much of the outcome data is industry funded. In addition, much of it is done in adults.

So, the test’s not perfect, but what harm can it do? As described in the FDA warning and as seen in real life, patients and doctors may follow the red, yellow, and green suggestions of the reports without fully understanding how the company made those decisions. The clinical decision is then made to forego a first line medication in favor of a medicine suggested by the tests, a medicine that may not have as much evidence for efficacy, and in pediatrics, may not have even as much evidence for safety

How does one get pharmacogenetic testing? Testing has become easier and more financially attainable. A phone call or email to one of the limited companies that perform this testing will result in a representative signing your practice up and sending you some starter kits. A simple cheek swab is all that is required of your patient along with insurance information, and a consent for any costs.

But where does that leave us?

Patients and doctors need to understand what these tests can and cannot do. Nobody should be promising that a simple check swab will determine the medicine and dosage that’s right for any child.

Starting with a first line medication for children and adolescents for the diagnosed disorder is still the best starting point.

However, if a child has already had the testing, and you are presented with a report, it is important to be able to understand the report and not just skip to the color-coded graphics. Explain to your patient that the report may help you avoid a medication that may cause problems, but it is less likely to help you find a medicine that will work.

Finally, if you have a patient for whom you have struggled to find the right medicine, a patient for whom medicines seem to never work or to cause way too many side effects, a call to Project TEACH to discuss pharmacogenetic testing as well as other options to improve response is definitely in order!

By Rachel A Zuckerbrot, MD

More detailed information about Pharmacogenetic Testing can also be viewed on the Project TEACH website at this link: https://projectteachny.org/wp/blog/