Pharmacogenomics: Understanding the Basics

Pharmacogenomics (phar·ma·co·ge·no·mics) may be a multisyllabic, hard-to-pronounce word. However, the relatively new field already has helped many, many people.

What is Pharmacogenomics?

When you go to see your healthcare provider with a health problem, you are looking for answers regarding your symptoms: what is wrong with me and how do we fix it?

To help you, the provider reviews the information you have given to them and, if necessary, gathers additional data through diagnostic testing. Using this information, a healthcare provider will recommend treatment options.

Some treatment options could include medication. Until recently, drugs have been developed in a “one size fits all” kind of approach. The field of pharmacogenomics has revolutionized how medications are prescribed and taken. Now, more and more providers are using pharmacogenomic testing for mental health treatment with medication.

“Psychiatry can be vague,” says Dr. Jay Tillman, psychiatrist, MD. “Symptoms can change, and side effects can be hard to determine. …Using a data-driven approach with actionable information in treatment decisions has proven to be useful in so many ways.”

Pharmacogenomics is a field of research that studies how a person’s genes affect how he or she responds to medications. This type of testing may help inform healthcare providers’ medication selection and dosing. While it cannot confirm which medications or doses will work for a patient, it can point out potential issues with medications. Pharmacogenomics uses information about a person’s genetic makeup, or genome, to choose the medication and dosage that are likely to work best for that person.²

“In the past, most drugs were designed to work on the population level rather than being targeted for the individual patient. By reversing that trend, pharmacogenomics helps to refine the focus of treatment and makes drugs more effective and less toxic,” according to an article in the Journal of Clinical Medical Research. “Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each person’s own genetic makeup. Environment, diet, age, lifestyle, and state of health all can influence a person’s response to medicines but understanding an individual’s genetic makeup is thought to be the key to creating personalized drugs with greater efficacy and safety.”

What is a Pharmacogenomic Test?

Pharmacogenomic tests evaluate a person’s DNA to determine how they may metabolize or respond to medications. This type of testing helps guide healthcare providers in choosing medications and dosing. While it cannot confirm which medications or doses will work for a patient, it can point out which medications to avoid.

The two types of genes studied in pharmacogenomics provide the data needed to personalize medication choices and dosages:

• Pharmacodynamic genes: these genes make proteins that affect how a medication works and what it does to the body
• Pharmacokinetic genes: these genes make proteins that affect how the body breaks down medications

“Many drugs that are currently available are ‘one size fits all,’ but they don’t work the same way for everyone,” states the US National Library of Medicine. “It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects (called adverse drug reactions).”

However, pharmacogenomic testing may help improve clarity regarding drug selection because these tests analyze clinically important genetic variations in an individual’s DNA. This information can be used by healthcare providers to better predict which medications may require dose adjustments, may be less likely to work, or may have an increased risk of side effects based on a patient’s genetic makeup.

Are genomics and genetics the same thing?

No, though it is a common mistake to use genetics and genomics interchangeably. Genetics is the study of a single gene and its role in how conditions are passed from one generation to the next. Genomics is the study of all parts of an organism’s genes.¹

How do my genes affect how medications may work for me?

When a medication doesn’t work well with your genes, you may not get the relief you need and you may have unwanted side effects. By gathering information about your genetic profile, you and your healthcare provider can make better informed decisions regarding your treatment. Medicines that align well with your genes may work better and with fewer side effects.

How Does Pharmacogenetic Testing Work?

For people who are depressed, antidepressants are often an important element of their treatment plan. However, finding a medication and dosage that’s effective without causing side effects can be a challenge. Many patients can try multiple medications and dosages without achieving a reduction in depressive symptoms.

One reason why is that everyone breaks down and responds to medications differently. Your genes can affect how quickly your body breaks down (metabolizes) medicine and how certain medicines work on the body. No two people have identical genetic profiles (unless they are identical twins). Some medications may work better with your unique genetic profile and some medicines might not work at all for you.

There are more than 20,000 genes in your body. Mostly found in the liver, the Cytochrome P450 system is a family of more than 50 genes that produce enzymes that metabolize medications, including antidepressants. Six of those enzymes metabolize about 90 percent of medications, according to an article in American Family Physician.

When you take an antidepressant, your body processes it in four steps:

1. Absorption. The process by which a drug enters the bloodstream. When you take a medication orally, it passes from your mouth to your gastrointestinal tract to your liver, and then it enters your bloodstream.
2. Distribution. From your liver, the medicine is carried throughout the body via the circulatory system. The drug molecules interact with various proteins and fat molecules, which can affect distribution. During this process, the medication starts to take effect.
3. Metabolism. Metabolic enzymes (which function based on your genetic makeup and other external factors) continue to process the medication in the liver so that it can be excreted.
4. Excretion. The removal of the medication from the body.

Your unique genetic profile determines the rate at which your body may metabolize and respond to a certain antidepressant. For example, if the antidepressant is broken down more slowly than normal, you may have too much medication in your body, which may lead to side effects. If an antidepressant is broken down more quickly than normal, you may not have enough medication in your body, which may be ineffective for treatment.

Additionally, research has found that people metabolize different medications differently. Based on your genetic profile, you may be a poor metabolizer for one enzyme, but an extensive metabolizer for another. There are four different metabolizer phenotypes:

• Poor metabolizer – You may break down some medications very slowly compared to normal. You may experience side effects at standard doses.
• Intermediate metabolizer – You may have a slower than normal rate of metabolism, and you may have too much medication at standard doses, potentially causing side effects.
• Extensive (normal) metabolizer – You have a normal rate of metabolism. You are predicted to have a normal amount of medication at standard doses.
• Ultrarapid metabolizer – You may break down some medications more quickly than normal. You may not have enough medication in your body to experience symptom relief.

Is the GeneSight test a pharmacogenomic test?

Yes, the GeneSight test is the leading pharmacogenomic test to help clinicians make better informed decisions about medication selection to treat mental health conditions. Its technology is backed by extensive research and supported by multiple clinical studies published in peer-reviewed journals.

How the GeneSight Test Helps Healthcare Providers Help Their Depressed Patients

It can be frustrating for the patient and the healthcare provider when the first antidepressant prescribed proves not to be an effective medication to relieve a person’s depressive symptoms. The GeneSight Psychotropic test may help reduce the length of time engaging in an extensive trial and error process.

“The trial-and-error process is where patients lose confidence. They also lose time and the opportunity to make good memories when they are feeling bad and you are experimenting with different medications,” says Dr. Ada N. Ifesinachukwu, MD. “They miss birthday parties, they drop out of school, their relationships suffer. You can’t get that time back.”

Dr. Ifesinachukwu provides one example of how the GeneSight Psychotropic test has helped her help her patients.

“One patient of mine had been on multiple medications with no improvement whatsoever. In fact, her husband and daughter said she ‘simply didn’t want to get better’ and that she wouldn’t leave the house. She arrived at my office the first time in a wheelchair (dropped off by her husband who went to wait in the car), because she had so many side effects and other conditions, including arthritis, thyroid problems and sleeping all the time.

Because she had tried so many medications, I ordered the GeneSight test right away. Every single medication that she had taken showed significant or moderate gene/drug interactions. I called her and told her that she is likely metabolizing the medicine very slowly, which may be contributing to these debilitating side effects. I created a plan to ween her off her current medication and start a new medication that had no gene/drug interaction.

After going through the detox program and getting on new medication, she started to feel better. In fact, the next time she came to my office, she was out of the wheelchair and drove herself to my office. She told me that ‘for the first time in 30 years I felt like I should. I’m living my life now.’ She and her husband are now traveling together.”

“When I first learned of pharmacogenomic testing – I’ll admit, I was very skeptical,” says Dr. Tillman. “I truly didn’t have a full understanding as to how it could be used. … Pharmacogenomic tests like the GeneSight test give useful information that aids in making treatment decisions. It doesn’t remove the clinician’s role in treatment decisions – it provides personal information about a patient’s genetic code for more insightful decisions.”

Depression remission is the goal of depression treatment. Dr. Ada says that she uses the GeneSight test because people are suffering. “I do not want someone to leave my office feeling worse – I want people to leave feeling better. I always fight for my patients to get better.”

To learn more about antidepressants and depression, read these articles at the GeneSight blog:

https://genesight.com/blog/patient/5-things-to-know-before-starting-antidepressants/

https://genesight.com/blog/patient/what-are-the-types-of-antidepressants/

https://genesight.com/blog/patient/will-taking-antidepressants-kill-my-libido/

To find a healthcare provider near you who offers the GeneSight test, follow this link: https://genesight.com/find-a-provider/

This genetic insight is for informational purposes only and does not constitute medical advice. Do not make any changes to your current medications or dosing without consulting your doctor.

The GeneSight test must be ordered by and used only in consultation with a healthcare provider who can prescribe medications. The GeneSight test results are one element of a clinician’s decision-making process, which must be tailored to the specific circumstances of each patient.

If you are a healthcare provider and interested in learning more about the GeneSight test, please contact us at 855.891.9415. If you are a patient, please talk with your doctor to see if the GeneSight test may be helpful.

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. © 2018 Assurex Health, Inc. All rights reserved.

References

1. Cardiology Today. Sept. 12. 2015 https://www.healio.com/cardiology/genetics-genomics/news/online/%7B6cdf2745-8257-40e4-ae0c-4f1fa7193d03%7D/genetics-vs-genomics
2. National Human Genome Research Institute https://www.genome.gov/27530645/