What are non-stimulant Attention Deficit Hyperactivity Disorder (ADHD) medication options?

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From the Guidelines

Non-stimulant ADHD medication options are available, including atomoxetine, clonidine, and guanfacine. These medications have been shown to be efficacious in treating ADHD, although their effect sizes are generally smaller than those of stimulants 1.

Key Characteristics of Non-Stimulant Medications

  • Atomoxetine: a selective norepinephrine reuptake inhibitor, with a medium effect size, and potential benefits including "around-the-clock" effects, and lower risk of decreased appetite and growth problems compared to stimulants 1.
  • Clonidine and Guanfacine: selective α-2 adrenergic agonists, with medium effect sizes, and potential benefits including "around-the-clock" effects, and utility in treating comorbid sleep disorders, substance use disorders, and disruptive behavior disorders 1.

Potential Advantages and Disadvantages

  • Advantages: non-stimulant medications may be preferred in certain cases, such as comorbid substance use disorders, disruptive behavior disorders, or tic/Tourette's disorder, due to their non-controlled status and "around-the-clock" effects 1.
  • Disadvantages: non-stimulant medications may have smaller effect sizes compared to stimulants, and may be associated with adverse effects such as somnolence, dry mouth, and decreased appetite 1.

Clinical Considerations

  • Dosing and Administration: atomoxetine can be administered in the morning or evening, while clonidine and guanfacine are generally preferred in the evening due to their sedating effects 1.
  • Monitoring and Adherence: regular assessment of medication adherence and potential issues is crucial, and factors such as patient attitudes, physician-patient relationship, and family support should be evaluated and addressed 1.

From the Research

Non-Stimulant Medication Options for ADHD

Non-stimulant medication options for Attention Deficit Hyperactivity Disorder (ADHD) include:

  • Atomoxetine, a selective norepinephrine reuptake inhibitor 2, 3, 4, 5
  • Guanfacine, an alpha-2 adrenergic agonist 2, 3, 5
  • Clonidine, an alpha-2 adrenergic agonist 2, 3
  • Tricyclic antidepressants (TCAs) 3, 4, 5
  • Bupropion, an antidepressant with noradrenergic and dopaminergic properties 3, 5
  • Viloxazine, an antidepressant with noradrenergic properties 5
  • Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist 5
  • Metadoxine, a drug with potential noradrenergic and dopaminergic effects 5

Mechanisms of Action and Efficacy

These non-stimulant medications have been shown to be effective in treating ADHD symptoms, with varying mechanisms of action:

  • Atomoxetine works by selectively inhibiting the reuptake of norepinephrine 2, 4
  • Guanfacine and clonidine work by stimulating alpha-2 adrenergic receptors 2, 3
  • TCAs work by inhibiting the reuptake of norepinephrine and serotonin 3, 4
  • Bupropion works by inhibiting the reuptake of norepinephrine and dopamine 3, 5

Safety and Tolerability

The safety and tolerability of these non-stimulant medications have been evaluated in various studies:

  • Atomoxetine has been shown to be generally well-tolerated, with few side effects 2, 4, 5
  • Guanfacine and clonidine have been shown to be effective, but may have side effects such as sedation and dry mouth 2, 3
  • TCAs have been shown to be effective, but may have side effects such as sedation, dry mouth, and constipation 3, 4
  • Bupropion has been shown to be effective, with a more favorable side-effect profile than TCAs 3, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Current Pharmacological Treatments for ADHD.

Current topics in behavioral neurosciences, 2022

Research

Non-stimulant medications in the treatment of ADHD.

European child & adolescent psychiatry, 2004

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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