Updated May 8, 2024. 

When parents see their child continually struggling to concentrate and complete homework on time, they may seek to confirm ADHD diagnosis and treatment. Often, medication can help children (and adults) diagnosed with ADHD improve focus and memory and inhibit impulsive behaviours. Although ADHD medication seems to be an easy solution to a child’s behavioural problems, parents should be aware of the health risks posed by commonly used ADHD drugs. So the question is: How safe are ADHD medications for children?

Depending on the drug and dose taken, children with ADHD have an increased risk of sleep issues, a reduced appetite that may lead to low body weight or stunted growth, impacted blood pressure and heart rate, and, more rarely, psychosis. There is also no surefire medication that works for each child. It often takes a period of trial and error to find a prescription that fits. In this review, we will describe the types of drugs prescribed for ADHD and how pharmacogenetic testing can help to optimize treatment and reduce the health risks of ADHD medications.

What are the types of ADHD medications for children?

Stimulants

Psychostimulants such as amphetamines and methylphenidates are the most commonly prescribed medications for ADHD:

Amphetamines, dextroamphetamine (Dexedrine), dextroamphetamine-amphetamine (Adderall, Mydayis), lisdexamfetamine (Vyvanse).

Methylphenidates (Concerta, Ritalin) and dexmethylphenidate (Focalin)

Both amphetamines and methylphenidates are available in short-acting and long-acting forms. The right medication and dose vary from child to child and depend on factors such as weight and inherited liver metabolism. Pharmacogenetic testing assesses drug metabolism in the liver and can reduce the time needed to find appropriate ADHD medication and the correct dose.

Amphetamine, as well as dextroamphetamine, is cleared out of circulation by the CYP2D6 liver enzyme. Inherently reduced amphetamine clearance can lead to drug-induced side effects. Amphetamines, when concurrently used with antidepressants, can lead to dangerously high serotonin levels (serotonin syndrome). Children and adults who are Poor or Ultrarapid metabolizers should avoid amphetamine.

Amphetamines carry a higher risk for agitation and psychotic or manic symptoms in teens. Stimulant medications may also cause increased blood pressure and heart rate. Contact the doctor immediately if your child has worsening behaviour, sees or hears things that aren’t real, experiences shortness of breath, or too-rapid heartbeat.

Methylphenidate use also carries similar risks, but the CES1A1 enzyme metabolizes this medication. Unfortunately, to date, there are no tests to assess its function reliably.

Other Medications

Atomoxetine (Strattera) is another drug metabolized by the CYP2D6 enzyme. Fine-tuning the atomoxetine dose can take significant time. Pharmacogenetic tests can give your child’s physician insights into the anticipated dose range. Over 25% of children are Poor or Ultrarapid metabolizers. Poor CYP2D6 metabolizers require a lower dose. Ultrarapid metabolizers are less likely to respond at the standard dose.

Bupropion (Wellbutrin SR, Wellbutrin XL) is recommended as a first-line option in adult patients with ADHD and comorbid major depressive episodes by the Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force. It is also prescribed for children and adolescents in some instances. Bupropion is a pro-drug that is activated by the CYP2B6 enzyme. Almost 50% of people in Canada have reduced or absent CYP2B6 activity and may not benefit from the average bupropion dose.

Guanfacine (Tenex) was originally approved by the FDA to treat hypertension, and later in 2010 for ADHD treatment in children. Guanfacine is cleared by the CYP3A4 enzyme, which is involved in metabolizing over half of all medications. Because of this, it should be used with caution with other drugs such as antibiotics, antidepressants, and heart medications. Because it reduces blood pressure, it can cause fainting, sleepiness, headache, and other side effects. About 15% of people in North America have inherently reduced CYP3A4 activity and need a lower guanfacine dose to reduce the incidence of side effects.

Viloxazine, also known as Qelbree, is a type of medication used to treat ADHD. It belongs to the selective norepinephrine reuptake inhibitor class (SNRI) and is a non-stimulant medication. It is a good alternative for children who experience aggressiveness, hallucinations, and increased anxiety when taking stimulants. Viloxazine may also be helpful for kids who experience symptoms such as low mood, anxiety, or depression, as it acts as an antidepressant.

The mechanism of action of viloxazine is similar to atomoxetine, and it is also metabolized by the CYP2D6 enzyme and, to a lesser extent, by UGT1A9 and UGT2B15. It blocks a liver enzyme called CYP1A2, which metabolizes caffeine. As a result, viloxazine makes kids more sensitive to energy drinks containing caffeine, which should be avoided while taking viloxazine medication.

Body Weight and Growth

Amphetamine and methylphenidate both reduce appetite and may cause delayed or stunted growth. In a recent study, children receiving stimulant medication with declines in body mass were advised to enhance caloric supplementation, “drug holiday” when treatment is limited to school days, and to switch to short-release drug formulations. These strategies improved weight gain but did not improve height velocity. Atomoxetine may also lead to reduced weight, as clinical trials in obese women showed a positive impact on weight loss. In contrast, bupropion and viloxazine have a lower impact on appetite and might be a better treatment option for underweight children.

Increased risk of heart disease

A recent population study conducted in Sweden has found a potential link between stimulant ADHD medications and heart disease that can develop later in life. The study suggests that longer cumulative use of ADHD medication can increase the risk of hypertension and arterial disease. For each year of ADHD medication use, there is a 4% increased risk of heart disease. The risk is higher during the first three years of medication use, and then it gradually tapers off. Parents should consult their pediatrician and monitor blood pressure and heart rate changes over several months after starting stimulant therapy to assess the long-term effects.

ADHD medications for children are not the only option for treatment. Kids with attention deficit can also benefit from behaviour therapy and social skills coaching. Parent skills coaching and family counselling provided by a mental health professional can help, in addition to medication management. Psychologic advice may be needed for children with ADHD experiencing anxiety or depression.

Personalized therapy with ADHD medications for children

When it comes to determining the safety of ADHD medications for children, the answer is highly individual. Response to ADHD drugs varies from person to person and depends, in large part, on genetics. A pharmacogenetic test, such as Pillcheck, can help reduce the guesswork. Pillcheck assesses your child’s DNA to help guide the selection of medications toward those most likely to be safe and effective for your child based on their genetic profile.

What to expect from PGx for ADHD

It is important to note that many drugs used as first-line therapy for ADHD (including methylphenidates such as Ritalin, Concerta, and Biphentin) do not yet have enough clinical evidence to establish pharmacogenetic guidelines.

Pillcheck only reports on medications with established clinical guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and pharmacogenetic labelling information by the US FDA and Health Canada. We continue to monitor the research and will add methylphenidates to Pillcheck reports once clear and actionable guidelines are set.

The Pillcheck test covers several other medications used alone or in combination with other therapies for ADHD. We currently report the following ADHD drugs:

• amphetamine
• dextroamphetamine
• atomoxetine
• guanfacine
• bupropion (off-label)
• viloxazine

The Pillcheck Report flags drugs for which your child is at a higher risk of side effects. The accompanying pharmacist review provides practical insights into drug selection, dosage, and potential drug interactions to be avoided. This can be especially helpful if the first-line treatment for ADHD is not working well and alternatives are being considered.

Check medications covered by Pillcheck here.

Conclusions

• ADHD medications carry potential risks of significant side effects and impacts on your child’s development
• Pharmacogenetic testing can assist your child’s physician in the selection of appropriate ADHD drug and dose
• Careful drug dosing and drug holidays can help to reduce the risk of side effects and reduce long-term risks
• Psychological counselling for both children and parents can assist in developing ADHD coping strategies, reduce anxiety, and improve mood.

References

1. Vo K, Neafsey P, Lin C Concurrent use of amphetamine stimulants and antidepressants by undergraduate students 22 January 2015 Volume 2015:9 Pages 161—172
2. Waxmonsky JG et al. A randomized controlled trial of interventions for growth suppression in children with attention-deficit/hyperactivity disorder treated with central nervous system stimulants. J Am Acad Child Adolesc Psychiatry2019 Aug 29; S0890-8567(19)31929-X;
3. de la Torre R et al., MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant? Front Genet. 2012; 3: 235.
4. Zhang L et al.,  Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases. JAMA Psychiatry. 2023 Nov 22. doi: 10.1001/jamapsychiatry.2023.4294. Online ahead of print.PMID: 37991787.