Attention Deficit Hyperactivity Disorder (ADHD) is the most common neurodevelopmental disorder in children, occurring almost twice as often in boys compared to girls. The most observed symptoms are inattention, hyperactivity, and impulsivity, but the primary presenting symptoms can vary between individuals. ADHD is considered a chronic condition that can impact an individual in several ways, including academic performance, professional achievements, relationships, and daily functioning. Treatment often includes a combination of medication and behavioral therapy. In this post, we will compare atomoxetine versus stimulants in the treatment of ADHD.

Guidelines published in 2019 by the American Academy of Pediatrics (AAP) list psychostimulants (amphetamines, methylphenidate) as first-line treatment for symptom management in children six years and older. Methylphenidate may be considered in children four to five years old if moderate to severe symptoms persist despite adequate behavioral interventions (strong recommendation).

Stimulant vs Non-stimulant Treatment Options

Stimulant Medications	Non-Stimulant Medications
Methylphenidate (Ritalin, Concerta) Dexmethylphenidate (Focalin) Dextroamphetamine/Amphetamine (Adderall) Amphetamine (Adzenys ER, Evekeo) Dextroamphetamine (Dexedrine) Lisdexamfetamine (Vyvanse)	Atomoxetine (Strattera) Clonidine (Catapres, Kapvay) Guanfacine ER (Intuniv)

Note that these medications are FDA-approved for ADHD treatment for adults and children. Non-stimulant medications are considered second line after trials of stimulant medications have failed. However, they can be used as a first-line treatment if there is a concern for abuse potential. Clonidine and guanfacine are classified as antihypertensive medications and their longer-acting formulations can be used with ADHD. 

Stimulant Medication Pros and Cons

Pros:

• Highly effective for ADHD treatment
• Extended and immediate-release formulations are available
• Available in several formulations, including capsule, chewable tablet, orally disintegrating tablet, patch, and suspension
• Can be used in combination with guanfacine and clonidine

Cons:

• Dextroamphetamine/amphetamine formulations have a boxed warning that misuse can cause sudden death and serious cardiovascular events
• All stimulant medications have a high risk for abuse and addiction potential
• Contraindicated with comorbid cardiovascular conditions
• Relatively contraindicated in patients with anxiety, tension, agitation, hyperthyroidism, or a history of Tourette’s syndrome or other tic disorders

Atomoxetine Versus Stimulants Pros and Cons

Pros:

• Less risk for abuse and addiction potential
• Can be given once or twice daily
• Risk of serious cardiovascular events is considered extremely low

Cons:

• May take several trials of stimulant medications before atomoxetine is considered, as it is not a first-line treatment; however, it can be considered first-line if there is a significant concern for abuse by the patient or family
• Boxed warning for risk of suicidal ideation
• Strong CYP2D6 inhibitor; administration with other CYP2D6 inducers or inhibitors can affect dosing considerations (find more examples of drug interactions with CYP2D6 here)
• Limited evidence to support the safety and efficacy of its use in combination with stimulant medications

Additional Considerations – Atomoxetine Versus Stimulants

When comparing atomoxetine versus stimulants, there are some important similarities in the adverse effect profile. Both can cause decreased appetite, GI upset, and weight loss. In addition to these, Both classes of medications have the potential to affect growth development in children, as well as cause increased heart rate and blood pressure. A cardiovascular assessment is recommended before starting any ADHD medications. Atomoxetine can cause somnolence and has been rarely associated with priapism. Ultimately, the decision to initiate ADHD medications, especially in elementary-aged children, depends on the clinical assessment, symptom severity, and the benefits and risks of estimated developmental impairment, safety risks, and potential consequences if medications are or are not initiated. 

This article was written by Sarah Zahirudin, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP

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References:

1. Elmaghraby R and Garayalde S. What is ADHD? American Psychiatric Association. June 2022. Available at: https://www.psychiatry.org/patients-families/adhd/what-is-adhd.

2. Wolraich M, Hagan J, Allan C, et al. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. 2019;144(4). Available at https://publications.aap.org/pediatrics/article/144/4/e20192528/81590/Clinical-Practice-Guideline-for-the-Diagnosis?autologincheck=redirected.