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Large Scale Study Compare Effects of Two Classes of ADHD Drugs in Preschool Kids

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Key Takeaways

  • Although the first line of treatment for preschool-age kids with ADHD is behavioral counseling, some children may need to take medication for the disorder.
  • A first-of-its-kind study analyzed the effectiveness and side effects of two classes of ADHD medication, stimulants and alpha 2-adrenergic agonists.
  • The researchers found that both classes of drugs have benefits, but different side effects.

Different types of medication may be prescribed for children with attention deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder that is characterized by symptoms like hyperactivity, impulsiveness, and inattentiveness.

A recent multi-institutional study carried out by a team from the Developmental-Behavioral Pediatrics Research Network (DBPNet), led by Children’s Hospital of Philadelphia (CHOP), analyzed the effectiveness and side effects of two main classes of ADHD medication prescribed to preschool-age children.

The research, published in JAMA, found that both classes of drugs have benefits, but suggests that prescribing decisions should be made based on the individual patient, due to different side effects. According to the Centers for Disease Control and Prevention (CDC), ADHD medication can help kids manage those symptoms and control behaviors that may be problematic at home and school.

Several different classes of drugs are FDA-approved to treat ADHD in children, the most common of which are stimulants like methylphenidate (Ritalin). Another type of medication widely prescribed for ADHD is alpha 2-adrenergic agonists, such as guanfacine (Intuniv).

Studying the Benefits and Side Effects

The researchers reviewed the electronic health records of 497 children, who were patients at seven DBPNet outpatient developmental-behavioral pediatric practices between January 2013 and July 2017.

Each child was under age 6 when they were first prescribed a stimulant (322 children or 65%) or alpha 2-adrenergic agonist (175 children or 35%). 

Nathan Blum, MD

The first-line treatment of preschool-age children with ADHD should be family behavioral counseling. When children do not improve sufficiently with behavioral counseling, medication should be considered,

— Nathan Blum, MD

Both groups reported an improvement in symptoms, but the benefits were slightly greater in the children who were treated with stimulants (78% compared to 66%). 

When it came to side effects, children treated with alpha-2 adrenergic agonists reported lower rates of moodiness/irritability (50% vs. 29%), appetite suppression (38% vs. 7%), and difficulty sleeping (21% vs. 11%) than those taking stimulants. The only side effect that was more common in children taking alpha 2-adrenergic agonists than those taking stimulants (38% vs. 3%) was daytime sleepiness.

Important Research

This study is the first of its size to report on the rate of improvement and side effects of alpha-adrenergic agonists in preschool age children. “These drugs are increasingly being used to treat preschool aged children with ADHD, but there is almost no published information of their effectiveness or side effects in this age group,” says senior author Nathan J. Blum, MD, Chief of the Division of Developmental and Behavioral Pediatrics at CHOP. 

Of particular interest to the researchers was that children younger than 4 years old who were prescribed an alpha 2-adrenergic agonist were likely to continue taking it for longer than if they were prescribed a stimulant. On the other hand, children ages 5 to younger than 6 were likely to continue using the medication for longer if they were prescribed a stimulant. For the in-between group (ages 4 to 5), there was no notable difference between the types of medication. 

What This Means For You

If your child has been diagnosed with ADHD and your doctor is recommending prescription drugs, it's completely natural to have concerns about the effects of medication.

Remember, each child responds in their own way to different meds—there's no set formula. It may involve some trial-and-error, but if you pay close attention to your child's symptoms and how they respond to different ADHD drugs, and stay in close contact with your medical team, you're on the right path.

“Our study showed that not only are medications like guanfacine being used to treat ADHD in preschool-age children, about 35% of the time they are the first medication prescribed,” explains co-author Elizabeth Harstad, MD, MPH, an attending physician at the Boston Children’s Hospital’s Developmental Medicine Center.

“I think it was interesting that the youngest children who were started on an alpha-2 adrenergic agonist medication (like guanfacine) stayed on the medication longer compared to those started on a stimulant. This suggests the alpha-2 adrenergic agonist medications may be more tolerable for the youngest children, although additional research is needed to confirm this," says Harstad. 

Elizabeth Harstad MD, MPH

I think it was interesting that the youngest children who were started on an alpha-2 adrenergic agonist medication (like guanfacine) stayed on the medication longer compared to those started on a stimulant.

— Elizabeth Harstad MD, MPH

Dr. Blum emphasizes that "The first-line treatment of preschool age children with ADHD should be family behavioral counseling. When children do not improve sufficiently with behavioral counseling, medication should be considered,” he says.

“Our study suggests that it would be reasonable for clinicians to consider using alpha-adrenergic agonists for younger preschool age children with ADHD as stimulants have high rates of side effects such as moodiness/irritability, sleep problems, and decreased appetite.” 

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  1. Harstad E, Shults J, Barbaresi W, et al. α2-Agonists or stimulants for preschool-age children with attention-deficit/hyperactivity disorder. JAMA. 2021;325(20):2067-2075. doi:10.1001/jama.2021.6118

  2. Centers for Disease Control and Prevention. Attention-deficit/hyperactivity disorder (ADHD) treatment. Updated September 21, 2020.