Stimulants for Children with ADHD

Stimulants work by blocking the reuptake of both dopamine and norepinephrine on the presynaptic neuron, increasing the amount of neurotransmitter available in the presynaptic cleft. This is true of both major classes of stimulants, the methylphenidate class and the amphetamine class. The amphetamine class also enhances presynaptic dopamine release.

Food and Drug Administration (FDA) approvals

Methylphenidate is FDA approval for the treatment of ADHD in children aged 6 years and older.

Mixed amphetamine salts are FDA approved for the treatment of ADHD in children aged 3 years and older.

Evidence base for stimulants in the treatment of ADHD in children and adolescents

• Over 100 randomized clinical trials have supported the “robust behavioral efficacy” of stimulant medications for ADHD.
• 75% of children with ADHD respond to the first stimulant medication.
• 90% respond after a change to a second stimulant.
• Preschool-aged children have poorer symptom response to stimulants than do older children.
• Preschool-aged children are more likely to present with emotional outbursts, irritability, trouble falling asleep, and repetitive thoughts or behaviors with stimulant treatment.  
• No behavioral intervention is superior for core ADHD symptoms, but behavioral intervention and support may be needed for symptoms that accompany ADHD.

Stimulants fall into 2 groups: the methylphenidate group and the amphetamine group.  

Methylphenidate comes in immediate and sustained-release forms, as does its d-isomer, dexmethylphenidate.

The immediate release forms last about 4 hours and are generally dosed morning, noon, and 4 pm.

Immediate-release tablets may be crushed and mixed with soft food.

Dexmethylphenidate dosing is ½ that of methylphenidate.

Extended-release formulations vary by duration of action and delivery mechanism.

Immediate Release Methylphenidate and Dexmethylphenidate Formulations

Methylphenidate and Dexmethylphenidate Extended-Release (ER) Formulations, Oral

Methylphenidate Prodrug Formulations, Oral

Methylphenidate Transdermal Formulation

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The unit dose of immediate-release mixed-salts amphetamine, or Adderall, lasts a little longer than does a dose of immediate-release methylphenidate.  The extended release form mimics giving 2 doses about 4-5 hours apart, and can come close in duration of action to methylphenidate given 3 doses.   Some patients will still need a supplemental after school dose.

Other extended-release formulations vary by duration of action and delivery mechanism.  Lisdexamfetamine dimesylate (Vyvanse) is an amphetamine pro-drug of d-amphetamine bound to lysine which is hydrolyzed in the gut and liver, making it a drug of lower abuse potential.

Immediate Release Amphetamine Formulations

Extended-Release (ER) Amphetamine Formulations

Amphetamine Prodrug Formulation, Oral

Amphetamine Transdermal Formulation

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Ideal dosing of stimulant medications provides excellent ADHD symptom control over the period of the day when the child most needs it, with minimal side effects.  

In young or treatment-naïve patients, start at the lowest dose and increase as frequently as every 1-2 weeks as tolerated to achieve good symptom control, confirmed by parent and teacher rating scales.

Experts differ on whether to start with immediate-release or extended release formulations.

Immediate-release formulations allow greater precision in dosing over the course of the day.  They also allow lower dosing in younger children who may do best 2.5 mg of either methylphenidate or mixed amphetamine salts per dose.

Extended release formulations allow the convenience of a single daily dose, not having to take medication at school, and potentially more consistent coverage over the day.

Some patients will need a combination of extended- and immediate-release medications to cover their day. 

In general, increasing the dose of the stimulant increases its effectiveness and its duration of action up to, but not longer than, its expected duration of action.  So if a previously effective dose of a 10-12-hour stimulant formulation now lasts only 8 hours, increasing the dose should bring the duration back up to 10-12 hours.

If increasing the dose of stimulant does not improve symptoms or results in unacceptable side effects, consider switching to a different stimulant.

When switching from a relatively high dose of one stimulant to another stimulant, start the second stimulant at a low-medium dose. 

For more information:

Stimulant Dosing Strategies to Cover the Day in Your Patient with ADHD

Decreased appetite, weight loss:  Monitor height and weight.  Body mass index (BMI) may drop to an acceptable level and plateau.  Time meals outside the period of maximum stimulant action.  A good breakfast and a later-than-usual dinner may help.  

Difficulty getting to sleep, especially if dose lasts until late in the day: Sleep problems are common in people with ADHD so get a sleep history pre-treatment.  Encourage sleep hygiene.  Consider a shorter-acting stimulant formulation or dosing earlier in the day.  Consider adding melatonin.

Increased blood pressure or pulse: generally 3-5 mm Hg increase in blood pressure; 4-6 bpm in pulse.  Monitor, especially in patients with borderline hypertension.

Irritability or emotional sensitivity, especially in younger children: this may be transient, so waiting is an option.  If symptoms are not tolerable, discontinue the stimulant, try a different stimulant, or consider a non-stimulant.  A rechallenge with the same stimulant when the child is older is unlikely to cause the same effect.

Picking behaviors or stereotypies, such as biting lips, pulling eyelashes: these are distinct from tics, and may be clearly related to the stimulant.  If a short trial off and rechallenge are associated with cessation of and resumption of the stereotypy, consider stimulant change, or consider a non-stimulant.

Tics and tic disorders frequently co-occur with ADHD, and historically stimulant medications have been associated with worsening of tics.  Recent studies suggest that is not the case.  Treatment discussions balancing the benefits of ADHD symptom control with perceived impact on tics should involve the patient and family. 

Slowing of linear growth: Studies are inconsistent regarding the impact of stimulants on final height but a recent analysis of data from participants in the MTA Study suggests that there may be as much as 1.6 inches in reduced growth among patients who consistently used stimulants for 16 years (Greenhill 2020).  Recommendations continue to include the monitoring of height and weight adjusting foods and mealtimes to maximize caloric intake, and to consider periods off medication.  

No regular laboratory monitoring is indicated in the use of stimulants.  

Cardiac risk evaluation:  ECG, and possibly cardiology consultation, are only indicated if there are indications of possible heart disease in the history and/or physical exam.  See the algorithm in the AAP policy statement on cardiac monitoring.  Perrin et al PEDIATRICS Volume 122, Number 2, August 2008.

Regular monitoring of height, weight, blood pressure and pulse is essential for all pediatric patients taking stimulants.

There are few significant drug interactions between stimulants and other medications commonly used in pediatric patients.  The amphetamine class is metabolized by CYP450 2D6.  Methylphenidate is metabolized by hepatic and peripheral esterases has minimal CYP interactions.  

Pediatric patients on antihypertensive medications should have close blood pressure monitoring as stimulants are titrated. 

Once ADHD symptom control is achieved, patients may continue on stimulant medication indefinitely.  Dosing is not strictly weight-based but as children grow they may require an increased dose to effectively cover their ADHD symptoms across their daily activities.  

Many families will opt for a trial off medication for their child at some point, either intentionally or by default.  Such trials off can be instructive in showing how the child functions without medication and what ADHD symptoms continue to be impairing. 

Choices about continuing ADHD medications increasingly involve the child as they move into adolescence.  Thoughtful consideration of a patient’s concerns about side effects should be part of the treatment alliance.  ADHD medication may be thought of as a tool that helps the patient achieve their goals.  Other tools may be available. 

More information can be found here:

The ADHD Medication Follow-up Visit

There is no discontinuation syndrome with stimulant medications and no need to taper the dose.

Some patients or parents may prefer that the child only take stimulants on school days. This strategy does not affect the efficacy of the medication on the days it is taken. It is worth understanding the rationale behind this preference. If improved ADHD symptom control on weekends allow the child to function better cognitively and socially, encourage weekend use. 

There are many stimulant medications on the market.  They are essentially all variations of methyphenidate and amphetamine products.  There is no way to predict which medication class or formulation is going to be most effective for any individual child or adolescent.  

Your initial medication choice will be either a methylphenidate or amphetamine product, and your formulation choice will be based on the duration of action you want to achieve (generally shorter for young children, longer for teens), whether the patient can swallow a pill or needs a formulation that can be sprinkled or mixed with liquid, and insurance coverage. 

We recommend that you get comfortable with 1-2 medications in each class that are on most formularies seen in your practice, and start with the same medication most of the time, switching to a medication of the other class if you get minimal response with the first one.  

This ADHD treatment algorithm illustrates this approach. 

• ADHD Recognition and Diagnosis (Mini-lesson)
• ADHD Stimulant Prescribing & Management  (Mini-lesson)
• The ADHD Medication Follow-up Visit  (Mini-lesson)
• When to Use a Non-stimulant Medication for ADHD  (Mini-lesson)
• Stimulant Dosing Strategies to Cover the Day in Your Patient with ADHD  (Mini-lesson)
• Stimulant Dosing Strategies to Cover the Day in Your Patient with ADHD  Watch & Listen | Download & Read

Greenhill, L., Kollins, S., Abikoff, H., McCracken, J., Riddle, M., Swanson, J., McGough, J., Wigal, S., Wigal, T., Vitiello, B., Skrobala, A., Posner, K., Ghuman, J., Cunningham, C., Davies, M., Chuang, S., & Cooper, T. (2006). Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 45(11), 1284–1293. https://doi.org/10.1097/01.chi.0000235077.32661.61

Perrin, J. M., Friedman, R. A., Knilans, T. K., the Black Box Working Group, & the Section on Cardiology and Cardiac Surgery. (2008). Cardiovascular Monitoring and Stimulant Drugs for Attention-Deficit/Hyperactivity Disorder. Pediatrics, 122(2), 451–453. https://doi.org/10.1542/peds.2008-1573

The MTA Cooperative Group. (1999). A 14-Month Randomized Clinical Trial of Treatment Strategies for Attention-Deficit/Hyperactivity Disorder. Archives of General Psychiatry, 56(12), 1073–1086. https://doi.org/10.1001/archpsyc.56.12.1073