Pharmacogenetic testing involves testing a person’s genetics to find out how a certain drug would work in that person. Learn the pros and cons of this testing.
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.
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.
Most parents of children with ADHD are familiar with stimulant medications. These include medicines in the ritalin and adderall family. There are many brands and formulations, but they are given in the morning and wear off at some point in the day. One of the problems is that when kids wake up, they are not medicated, which makes getting out the door a daily struggle. There’s a new technology that’s designed to allow medicine given at night to start working in the morning. This is different from the non-stimulant ADHD medicines that are used at night. Is a bedtime stimulant right for your child?
As this was only recently announced and is not yet on the market, I have no experience in using this novel medicine. I wanted to learn about it and thought I’d share what I learn, but I am not promoting its use since I have no experience with it.
I want to caution people who it will take quite awhile before this will be covered on insurance plans and available for mainstream use. It’s good for parents to be aware of what’s in development, which is why I’m writing about as I learn, but you must talk to your own physician about what medications are right for you or your child.
Most of the information about the new medicine is from the company that is developing it, Highland Therapeutics. This is not an unbiased source.
Stimulant vs Non-stimulant medicines
You might know kids who have ADHD medicines that already work in the morning, so you might be wondering what benefit this new system offers.
The non-stimulant medications can continue to work in the morning. This new delivery system is for stimulant medicines. For many kids, the stimulant medicines simply work better for the majority of the daytime hours, even though they don’t last as long as the non-stimulants.
The FDA has approved Jornay PM, a medication that uses a new drug delivery system for methylphenidate, one of the two main stimulants used for ADHD. The company that makes this, Ironshore Pharmaceuticals, is also working on one for amphetamine, but it has not yet been approved.
Jornay PM is expected to be available in the first part of 2019. This does not mean that your pharmacy will stock it or that insurance will cover it. I do not know how it will be priced, but typically new medicines are expensive.
Methylphenidate is the active ingredient commonly referred to as ritalin. For many years we have had short acting and long acting forms of ritalin to use for people with ADHD. The short acting medicines generally last 3-4 hours and the long acting last 6-12 hours.
The new formulation of methylphenidate in Jornay PM is designed to be given at night so that it begins to work in the morning. The time release will allow the child to fall asleep without any of the active ingredient taking effect until several hours later. The idea is to figure out the timing so that when the child wakes, the medicine is already taking effect.
Why is this needed?
Many parents of kids with ADHD know the struggle of getting out the door in the morning.
While many kids can be expected to follow the morning routine of getting up, eating breakfast, brushing teeth, and dressing, kids with ADHD often get lost in this process. Every day.
The distractibility is not their fault. Getting ready in the morning requires many steps. Anything that requires time management and organization is difficult for people with ADHD.
The medicines they take typically take to help with these functions take about an hour to take effect. They need this medicine to be able to stay on task and help with executive functioning skills, not just to do school work.
There are certainly things that can be done to help that don’t involve medicine. Many kids benefit from putting clothes out and packing backpacks the night before. Charts with all the daily expectations can help kids visualize what needs to happen.
But they still struggle to stay on task without medicine. They often run late. Families fight despite the best intentions. When kids finally get out of the door, homework or needed materials are often forgotten. Self esteem is impaired with these daily struggles.
Many parents ask for help with morning struggles
Some kids have benefited from a non-stimulant for this purpose. Non-stimulants, such as guanfacine, clonidine, and atomoxetine, can be effective upon waking. Guanfacine and clonidine can help kids sleep as well, which is an added bonus to kids with ADHD, since many struggle with sleep issues. These medicines can be used alone or with stimulant medicines, but they aren’t effective for everyone.
Other parents have snuck into bedrooms to put a methyphenidate patch on their child so it starts to work before the child wakes. While this works well for kids that respond well to methylphenidate, they are very expensive and many families cannot afford them. Some kids don’t like wearing a patch or they get skin irritation from them.
How does this work?
Jornay PM uses a delivery system called DELEXIS. In this system the beads with medication inside resist water and dissolving.
The beads do not release any medicine immediately. They travel through the small intestine without dissolving for about 10 hours. When they reach a part of our intestine called the ileum, they are able to start dissolving.
The medicine will be effective for many hours once it starts to be released. The delayed release layer starts to provide medicine about 10 hours after ingestion. Specific timing is affected by foods and drinks taken in the evening. It is recommended to be consistent with eating and drinking when taking this medicine.
Inside the bead deeper than the delayed release layer is an extended release layer. This releases the medication even later than the delayed release layer, to provide for many hours of benefit.
About 14 hours after ingestion starts the maximum concentration of medication levels. Absorption of the medication continues through the early evening.
Will it be right for your child?
All of this sounds great for the kids who need help from the first thing in the morning until later in the evening, but I will wait to see how it really works. We’ll all have to wait to see if it works as stated or not.
There are many treatments out there that are not approved for the purpose they are used. This sounds scary, but if done properly might be a good consideration.
Physicians sometimes use treatments that have not been approved for the purpose or an age group because they know from general experience that it works or they are at a loss from approved treatments failing and they need to try something else.
One example is using a shorter acting form of guanfacine (Tenex) that has not been approved to treat ADHD, but it has some advantages over the longer acting form (Intuniv) that is approved for ADHD. The short acting form can be broken, allowing slower titration of dose changes. The long acting form cannot be broken.
Another common example is the use of albuterol, a medicine that helps breathing with conditions that cause wheezing. It is not approved for use under 2 years of age, but it is commonly used for younger children with difficulty breathing — and it helps them breathe, which might keep them out of the hospital and off of supplemental oxygen.
I do not think that all non-approved medicines are good or bad. It is a very individual decision of what medicines to use. Discuss with your doctor if a treatment is approved or if they are using something that is not. Although this is relatively common among people who treat children because many drugs have not been tested in children and have been “grandfathered” into use through experiences that show benefit, be sure the provider is not picking something that has no basis or supporting evidence, especially if he or she profits from the treatment.
Be very wary of anyone who promises a cure – if one really existed everyone would use it.
Medications approved to treat ADHD
When a medication is needed to control symptoms of ADHD, the first line medications are the stimulants unless there are contraindications. Non-stimulant medications are not found to be as effective as stimulants in the majority of children, but they do have a place in the treatment plan for some children. They are sometimes used in addition to stimulants for optimal results.
For information on these medicines, see A Guide to ADHD Medications. It reviews how stimulants act on dopamine and norepinephrine and various time release patterns of different medicines.
I love the ADHD Medication Guide (different from the similarly named post above) because it lists the medicines approved to treat ADHD in a colorful chart that groups the medicines in an easy-to-read format.
Others are used off-label (no FDA approval for the purpose of ADHD treatment): Tenex, Catapres patch, antidepressants, and antipsychotics
Parents usually worry about medication side effects. This is a very legitimate concern, but must be balanced with the risks of not treating. Overall the medicines listed above are very well tolerated.
If a child has side effects to one stimulant, they can usually do well on a different class (methylphenidate vs amphetamine). When neither type is tolerated, a trial of a non-stimulant is indicated. If this isn’t tolerated, reconsider the ADHD diagnosis.
I often hear concerns that parents don’t want their kids changing their personalities or becoming “zombies”. If the right medicine is used at the appropriate dose, this is usually not a problem.
Finding that right medicine and right dose might take some trial and error. Work with your prescriber to get to the right one for your child.
Most commonly observed side effects of stimulants:
Appetite is often low in the middle of the day and more normal by supper time if kids take a long acting stimulant.
Good nutrition is a priority. Encourage kids to eat the healthy “main course” first and leave the dessert out of the lunchbox. They should have healthy snacks (think of mini-meals) after school when they get hungry.
Short acting meds improve mid day appetite since they wear off around lunch time. The downside is the child needs to take a dose around lunch time at school.
Kids are often very hungry in the evenings when medicines wear off, so encourage healthy foods at that time.
I have seen some kids who have a really hard time off medicine sitting down to eat. These kids actually gain weight better on medicine because they can finish the meal.
Some kids can improve their appetite with an appetite stimulant. I often use cyproheptadine if weight drops too much in a child. It works best if it is not used every day. I will have kids skip their cyproheptadine at least a couple days each week.
Trouble sleeping is common with ADHD — with or without medicines.
If it is due to the stimulant medicine still being active, trouble sleeping may be relieved by taking it earlier in the day.
If the child’s brain is too active in the evenings because the medicine wears off, learning relaxation exercises can help. Check out the Winding Down section of Sleep Tips for more details.
Moodiness is especially common as the medication wears off in the afternoon or evening and in younger children.
It makes sense if you consider that all day they are able to focus and think before acting and speaking, but then suddenly their brain can’t focus and they act impulsively.
Typically kids learn to adjust to the medicine wearing off as they mature.
Sometimes just giving kids 30 minutes to themselves and offering a healthy snack can help.
People with ADHD are more likely to have tics than the general population.
It was once thought that tics were caused by the stimulant medicines, but it is now thought that they happen independent of the medicine, and medicines might even help treat the tics.
Weight gain can be difficult for some kids on stimulant medications due to the appetite suppression on the medicine.
Studies have shown a decreased final adult height of about 1-2 cm (1/2 – 1 inch). For most people this small height difference is not significant compared to the benefits in self esteem, academics and behavior children gain on stimulants.
Rare side effects of stimulants
I have only seen two children who could not tolerate stimulants due to hallucinations, but it is very scary for the family when it happens.
Unless there is a significant family history of them, I don’t know a way to predict which child is at risk.
These are a contraindication for continuing that medication, but another type of stimulant or medication can be considered.
Cardiac (heart) problems are overall a rare complication of stimulants and often times are not a contraindication to continuing the stimulant medicine.
There is a small increase in blood pressure and heart rate, both of which should be monitored regularly while on treatment and if the treatment is stopped.
A cardiologist should be considered to further evaluate a patient prior to starting a stimulant if there is any of the following:
Shortness of breath with exercise not due to a known non-cardiac cause, such as asthma
Poor exercise tolerance compared to children of the same age and conditioning
Excessively rapid heart rate, dizziness, or fainting with exercise
Family history of sudden cardiac death or unexplained death (such as SIDS)
Family or personal history of prolonged QT syndrome, heart arrythmias, cardiomyopathy, pulmonary hypertension, implantable defibrillator or pacemaker
side effects for the non-stimulants:
Atomoxetine can cause initial gastroesophageal complaints (abdominal pain, decreased appetite), especially if the dose is started too high or if it is increased too rapidly.
It can also cause tiredness and fatigue when it is first started or if the dose is increased too quickly.
It can increase the blood pressure and heart rate, both of which should be monitored regularly during treatment with atomoxetine.
There is an increased incidence in suicidal thoughts, though uncommon, so children should be monitored for mood issues on this medication.
A rare complication of atomoxetine is hepatitis (inflammation of the liver with yellow jaundice and abnormal liver function labs). The hepatitis resolves with stopping the atomoxetine.
Guanfacine and clonidine
Guanfacine and clonidine both cause fatigue and tiredness, especially when first starting the medication or with increases in dose.
Both of these medications can lower the blood pressure and heart rate, and these should be monitored closely while on guanfacine or clonidine, especially when first starting and increasing dose.
Handouts for medicines
I absolutely love the handouts that Dr. Nerissa Bauer has made for ADHD medications. Click on the image’s caption to go to her website’s page for that handout. The two stimulant classes are first, followed by the non-stimulants.
Many parents benefit from support groups to learn from others who have gone through or are currently going through similar situations, fears, failures, and successes. Find one in your area that might help you go through the process with others who share your concerns. If you know of a support group that deserves mention, please share!
CHADD is the nationwide support group that offers a lot online and has many local chapters, such as ADHDKC. I am a volunteer board member of ADHDKC and have been impressed with the impact they have made in our community in the short time they have existed (established in 2012). I encourage parents to attend their free informational meetings. The speakers have all been fantastic and there are many more great topics coming up!
Many parents are surprised to learn how much anxiety can affect behavior and learning. To look for local support groups, check out the tool on Psychology Today.
Choosing schools for kids with ADHD and learning differences isn’t always possible, but look to the linked articles on ways to decide what might work best for your child. When choosing colleges, look specifically for programs they offer for students who learn differently and plan ahead to get your teen ready for this challenge.
Midwest ADHD Conference – April 2018
Check out the Midwest ADHD Conference coming to the KC area in April, 2018. I’m involved in the planning stages and it will be a FANTASTIC conference for parents, adults with ADHD, and educators/teachers.