When 11-year-old Jennifer was diagnosed with ADHD at the age of 8, her mom Katherine Patterson knew for certain that she didn’t want to use medication, except as a last resort. The Denton mom, whose name has been changed for privacy, tried everything — from major diet changes to therapy — to cope with the disruption caused by her daughter’s disorder, which included daily emotional outbursts and struggling grades.
“I knew medication would be the easiest route, but I was worried about the potential for side effects,” Patterson recalls.
When Jennifer’s self-esteem and friendships began to suffer because of her behavior, Patterson decided to give medication a try. Unfortunately, drug therapy definitely didn’t prove to be the easiest — or the most effective — antidote.
Jennifer was first prescribed Strattera, a nonstimulant class medication that is commonly offered for ADHD treatment because it is considered less addictive and offers fewer side effects than stimulant drugs. Almost immediately, she began experiencing muscle weakness in her legs that made it difficult to stand, as well as lethargy that left her sleepy — or asleep — for most of the day. While drowsiness is a common side effect with Strattera, Jennifer’s daytime sleepiness was borderline narcolepsy.
“She was calmer but only because she was too sleepy to do much of anything else,” Patterson says.
So the frustrated mom went back to Jennifer’s psychiatrist. This time, she was prescribed Concerta. But Patterson had reservations about giving Jennifer this new drug. She didn’t like the trial-and-error approach to helping her daughter cope.
Patterson’s not alone. According to the Centers for Disease Control, 1 in 5 boys and 1 in 11 girls are diagnosed with ADHD. Doctors typically choose a medication to prescribe for ADHD largely based upon their own professional experience with it, meaning if most of their patients have had favorable results with it, your child likely will too. But that’s not entirely true. And many of the families affected by ADHD find themselves, like Patterson, stuck in a system that relies heavily on an experimental approach to find the right prescription for their kids. Which begs the question: Why do some medications work for some kids and not for yours?
The Rise of Personalized Medicine
According to the Food and Drug Administration, an estimated 2 million hospitalizations occur yearly as a result of adverse drug reactions, and more than 700,000 people experience serious consequences as a result of those adverse drug reactions.
Finding the right drug and the right dose is part of the art of medicine. And it’s something that pharmacists, physicians and researchers have tried for decades to understand. Whether a medication will work depends on several factors including age, other medications the child might be taking, kidney function and more. But it also depends on whether the prescribed medication is best matched to a child’s genetic makeup. That’s right: The same genes kids inherit from their parents that determine characteristics such as eye color and blood type are also responsible for how the body processes medications.
A young and rapidly growing field in health care aims to provide this genetic information for drug therapy to physicians so they can take a more personalized approach to selecting the right medication and dosage for each child — and adult. For the last decade, pharmacogenetic testing has emerged as a promising tool. Pharmacogenetics is the study of how genes affect a person’s response to medications — the answer, perhaps, to that question of why some meds work for some kids and not for others. It’s because some kids rapidly metabolize a certain medication, while others might poorly metabolize that same drug — all based on their DNA.
Dr. Michael Jann, professor and department chair of pharmacotherapy at the University of North Texas Health Science Center in Fort Worth, explains it this way: “Everybody is different down to their genetic level. Pharmacogenetics tells us how the body handles a medication, or how it’s absorbed and metabolized. Another way to look at it is to say that it is how different people react differently to the same medication.”
The promise of pharmacogenetic testing is that people get the right dose of the right drug with one pain-free swab on the inside of the cheek. For patients with ADHD, this could define a better starting point when looking at drug therapy. Jann offers Strattera as an example: “Strattera is metabolized by a specific liver enzyme, and it turns out that 10 percent of the population is a poor metabolizer of this enzyme. [That means that] the poor metabolizer will have almost four times the amount of the drug in their bloodstream as a fast metabolizer. In other words, [the slow metabolizer] could have more side effects, but they wouldn’t know that unless they took a drug-gene test.”
Testing the Limits
So why isn’t every doctor in the Dallas-Fort Worth area subscribing to this?
The potential for using a pharmacogenetic test, which provides information about whether a certain medication might be effective, dosaging specifications and the potential for side effects, is clear. Some experts have made the optimistic claim that this personalized medicine being the norm is just a matter of time, and it might be, but as of now, pharmacogenetics isn’t without its limitations.
There’s the question of what the test actually measures. Today the most frequently used pharmacogenetic tests look for variations in the genes that carry instructions for making the enzymes in the liver that metabolize or break down drugs. Researchers say these tests don’t look at anything other than metabolic rate. Representatives from the companies making tests, companies like GeneSight, which offers ADHD pharmacogenetic testing, claim the test measures metabolic rate and efficacy.
And some say that the companies making the tests are actually misleading patients, but that hasn’t stopped moms from seeking the tests for their kids.
Until recently, you could have picked up a Harmonyx ADHD genetic test from the community pharmacy for under $100. Flower Mound Pharmacy was just one of the more than 7,000 pharmacies nationwide (RiteAid carried the test in nearly all its pharmacies) that offered the test to customers.
“Patients were usually referred to us before the physician would prescribe a medicine,” says pharmacy owner Dennis Song. “We would do a simple swab here in the pharmacy and then enter that information into a portal. Results were emailed to the patient and simultaneously faxed to the doctor.”
But the FDA ordered the removal of the Harmonyx tests from pharmacy shelves last November, citing that the tests were “patient-initiated” and considered “direct-to-consumer” and therefore required special approval through their agency.
GeneSight isn’t FDA-approved either, but it hasn’t been pulled from the system. The test is ordered by a doctor’s office and processed in a laboratory. The results filter medications into categories, showing which drugs a particular body is programmed to break down in a normal fashion and which drugs the body is not programmed to break down in a normal fashion. It’s important to note, however, that a “normal” result doesn’t necessarily mean the drug is going to be effective or free of side effects.
Testing the Waters
With the science of pharmacogenetics still finding its footing, the patient response is mixed.
For Linda Ferrell-Brooksbank, pharmacogenetic testing helped determine what medication would finally work for her son Alex, who was diagnosed with ADHD in the first grade.
“We had tried so many different ADHD medications, and I was feeling very frustrated that after several years of trial and error we still had not yet landed on the right one,” she says. “My feelings of exasperation led me to the GeneSight testing.”
Although she was warned by her psychiatrist that the test may not tell them exactly which drug would work best, she was willing to give it try. She had nothing to lose at that point.
When the test results came back, they showed only showed one drug, Strattera, that would supposedly metabolized effectively in Alex’s body. Ferrell-Brooksbank was shocked by the results. Her son had been taking stimulants with a variety of side effects for years, but they never considered a non-stimulant drug. Alex, now 13, has been on the non-stimulant for over a year and Mom is thrilled with the results. “I am more comfortable with the non-stimulants because I have noticed a dramatic decrease in side effects in my son,” she says.
Author Penny Williams, who has written several books on the ADHD and children topic, including What to Expect When Parenting Children with ADHD, Boy Without Instructions and The Insider’s Guide to ADHD, had an opposite experience when her son tried two different pharmacogenetic tests.
Luke was diagnosed with ADHD in 2008 before genetic testing for drug therapy was offered to patients. Like many kids, he was sensitive to several medications and had serious side effects, including psychosis and deep depression. Knowing this history, a therapist recommended pharmacogenetic testing when it became available. “We had gotten to the point where we were fearful to try anything else because it was so bad when it was bad,” Williams recalls.
The results? Even more frustrating for Williams and her son. It turns out that several of the drugs Luke had already taken — and had significant side effects with — were green-lighted for use.
“Obviously, the reason that he is sensitive to medication was not found in the genetic markers these tests looked for because this test was coming back with a green light for drugs we knew he definitely couldn’t take and do well with,” Williams explains. “That tells me that the test isn’t covering as much as they want you to believe it does. It’s not giving the whole picture, like a lot of consumers think that it does.”
Clearly pharmacogenetics isn’t a cure-all. In fact, even if you try the first medication at the top of your child’s personal list (results given to you from the lab), there’s no guarantee that it will work and be effective for his symptoms.
The Future of Pharmacogenetics
So there’s a reason pharmacogenetic testing isn’t routinely offered by your child’s physician yet: The usefulness of the test results are still a bit murky.
“Doctors are usually the last people to accept new technology,” Jann explains. “They want to see it work before they use it.” (See sidebar for more information about finding a doctor)
And experts disagree on the efficacy of the pharmacogenetic testing currently on the market. But it seems clear to all parties that genetic testing for drug therapy looks promising and may eventually have very helpful applications. In his 2015 State of the Union address, President Obama announced a Precision Medicine Initiative that uses pharmacogenetic tests to guide the use of certain medications “to bring us closer to curing diseases like cancer and diabetes — and to give all of us access to the personalized information we need to keep ourselves and our families healthier.”
The tests are currently being used successfully in treating children with leukemia to help with dosages and for those adults taking Plavix, a drug commonly used after heart attacks to prevent blood clots from forming. Tests found that nearly 30 percent of adults taking the drug cannot fully convert Plavix, making it less effective at preventing future heart attacks and strokes.
And consider this potential real-life application that testing could eventually provide you: You’re stuck in the ER with a hurt or sick child. Wouldn’t it be nice to hand the emergency room doctor your child’s pharmacogenetic test results so he can cross-reference the list with any medications your little one may need while she’s in the ER? That, experts say, is the future of medicine.
But Jann says we’re likely years away from that reality and routine genetic testing for drugs, explaining that we first have to have to better understand the genetics behind disorders like ADHD.
“We don’t have a genetic test for autism, and we don’t have a genetic test for ADHD,” he points out. “We don’t really understand the disease at the genetic level, and until we come up with a genetic marker for those disorders, we will never be able to learn everything we need to from these tests.”
Until then, parents like Patterson, who still hasn’t found the right medication for her daughter, will have to make do with the limits of genetic testing and the standard trial-and-error drug therapy. Pharmacogenetic testing is currently unavailable to Jennifer because it’s not covered by insurance.
“It would be a dream come true to have an affordable test that would tell me exactly what medicine my daughter needs,” Patterson laments. “Until that happens, we will keep hoping that the next thing we try will be the right answer.”