Pharmacogenetic Testing: Personalized Medicine

I've recently seen increasing numbers of parents who want testing to decide which medication to use for their child's condition before trying any medicines. Many admit that they don't know much about it and want to learn more. Pharmacogenetic testing involves testing a person's genetics to find out how a certain drug would work in that person. While that sounds like it would be fantastic to know, it has many limitations. We'll talk about the pros and cons below.

Traditional dosing of medicines

Before they can be approved to be used, drugs are tested in large groups of people.

Dosing schedules are determined based on safety and efficacy of the medicine, but this is in a group. It relies on information gathered from a mass of people, and majority rules. This means that whatever works for most people is what becomes the recommendations.

Although this works for most people, any individual can have a variation that is not seen with the large numbers in a group. We all know people that can't tolerate certain medicines. In the past we use family patterns to help predict tolerability. If a family member (or especially if multiple family members) report that certain medicines require lower or higher doses to be tolerated and effective, then we use that in our decision making for prescribing medicines. Of course it isn't a perfect way to do things, but it can help.

What is pharmacogenetic testing?

Pharmacogenomics is the study of how genes affect a person’s response to drugs. It's a growing field that involves using what we know about the person's genetic make up and how they will metabolize a medication. This can allow the prescriber to use certain medicines and not others, or begin with overall higher or lower doses than standard recommendations suggest.

It is personalized to a person's genetic makeup, so it's often called personalized medicine or precision medicine.

Many medicines work well for most people, but there are people who will metabolize certain things slowly, allowing the medicine to build up to toxic levels when dosed per standard amounts. Other people may require higher doses due to a very rapid metabolism. Some people should avoid certain medications all together. Knowing these dose adjustments and risks before even starting a medicine could be very beneficial!

Certain proteins affect how drugs work. Pharmacogenetic testing looks at differences in genes for these proteins. These proteins include liver enzymes that chemically change drugs. These changes can make the drugs more or less active. Even small differences in the genes for these liver enzymes can have a significant impact on a drug’s safety or effectiveness.

What are some uses in general pediatrics?

I'm limiting this discussion to uses that a general physician would use this type of testing. There are other uses for chronic diseases that are managed by specialists and beyond my scope.

Please realize that these are the commonly requested uses, not recommended uses.

ADHD

The most common time that I'm asked about this type of testing is for kids with ADHD.

Many parents are afraid of side effects of stimulants and have heard of other children who needed many adjustments of medication, both type of drug and dosing.

Starting a new stimulant medication can be frustrating, especially if it takes weeks or months to find what works. Parents would like to avoid that and start with the best.

Unfortunately the tests currently available do not predict which medicine will be most effective. They test how it will be metabolized.

Many people who show best tolerability for a certain drug may find that drug ineffective in managing their symptoms. This is due to many factors, but in the end still leaves us with the need to do a trial of various medicines to find the best one.

Failure to find a beneficial medicine based on these trials may lead to reassessment to be sure the diagnosis is correct. Proper diagnosis is not tested with the pharmocogenetic tests.

Anxiety and depression

Anxiety and depression medications are another type of medicine that has many options, and some respond to one better than another.

The traditional way to start is to look at family history (which is also a study of genetics, although included in the cost of your visit and doesn't include a lab). Unfortunately, many people do not know of family member's specific health details, especially what medicines they were on and what their reactions were.

When we pick a medicine, we start with low doses, and increase as tolerated and needed. If the first medication doesn't work or isn't tolerated, it is stopped and another is tried. This can prolong the time it takes to feel better, which is significant, and likely the reason people want a quick answer with a lab test.

Unfortunately, much like the ADHD testing mentioned above, the tests don't predict which medicine will manage symptoms best. They only predict how they will be metabolized.

Should you get tested?

I am excited for the future of personalized medicine.

We may no longer need to try multiple medicines to be able to see which are better tolerated. Starting near the target dose, rather than starting at a low dose and titrating up, which prolongs the time it takes to get to an effective dose, would be welcomed in many people.

Unfortunately, I think psychopharmalogical testing is not yet for prime time.

The FDA agrees. They've sent out warnings that these tests should not be used to help choose a medicine.

Just because your body will metabolize a medicine more slowly or rapidly doesn't predict if it will be effective to treat your symptoms.

It is still very costly and insurance companies resist paying for it. With high deductible plans, many people must pay the cost. With the new FDA warning, it is unlikely that insurance companies will cover the cost of these tests anytime soon.

It is being widely used in cancer and HIV patients and has helped to prevent significant side effects that often lead to hospitalization. From an insurance company standpoint, they're saving money by covering the test for these purposes. From a patient standpoint, they have added security that they will respond well to the treatment.

For more:

Pharmacogenomics and Personalized Medicine By: Jill U. Adams, Ph.D. (Freelance science writer in Albany, NY) © 2008 Nature Education Citation: Adams, J. (2008) Pharmacogenomics and personalized medicine. Nature Education1(1):194

ADHD Medicines: Starting out and titrating

PHARMKB

Addendum: 10/3/19

The New AAP ADHD Guidelines were released this week.

Pediatrics October 2019, VOLUME 144 / ISSUE 4 From the American Academy of Pediatrics Clinical Practice Guideline

Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

Mark L. Wolraich, Joseph F. Hagan Jr, Carla Allan, Eugenia Chan, Dale Davison, Marian Earls, Steven W. Evans, Susan K. Flinn, Tanya Froehlich, Jennifer Frost, Joseph R. Holbrook, Christoph Ulrich Lehmann, Herschel Robert Lessin, Kymika Okechukwu, Karen L. Pierce, Jonathan D. Winner, William Zurhellen, SUBCOMMITTEE ON CHILDREN AND ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVE DISORDER                      

The authors specifically state that this testing is NOT recommended.