Non-Stimulant Medication Options for ADHD in Children
Atomoxetine (Strattera) is the primary FDA-approved non-stimulant medication for ADHD in children, with extended-release guanfacine and extended-release clonidine as additional options when atomoxetine is not suitable. 1
First-Line Non-Stimulant: Atomoxetine
Atomoxetine selectively inhibits norepinephrine transporters, enhancing noradrenergic transmission in the prefrontal cortex, which helps improve executive functions impaired in ADHD 1.
Dosing Guidelines:
- Starting dose: 0.5 mg/kg/day
- Target dose: 1.2 mg/kg/day
- Maximum dose: 1.4 mg/kg/day or 100 mg/day (whichever is lower)
- Titration schedule: Dose adjustments typically every 7-14 days 1, 2
- Can be administered as a single morning dose or divided doses (morning and late afternoon) 2
- May be taken with or without food 2
Efficacy:
- Effect size of approximately 0.7 (compared to ~1.0 for stimulants) 1
- Therapeutic effects extend throughout waking hours, into late evening, and sometimes into early morning 3
- Full therapeutic effect may take 6-8 weeks to achieve 4
Clinical Considerations:
- Capsules should be taken whole, not opened 2
- No tapering required when discontinuing 2
- Screen for bipolar disorder before initiating treatment 2
- Requires daily compliance for effectiveness 5
Other Non-Stimulant Options
Extended-Release Guanfacine and Clonidine:
- Alpha-2 adrenergic agonists
- Recommended by the American Academy of Pediatrics as alternative non-stimulant options 1
- Limited number of studies documenting efficacy compared to atomoxetine 6
Bupropion:
- Has been used off-label for ADHD treatment 5
- Not FDA-approved specifically for ADHD
- May be considered when atomoxetine and alpha-2 agonists are not suitable
Tricyclic Antidepressants:
- Have shown efficacy in ADHD treatment
- Limited by side effect profile 6
- Generally considered after other non-stimulant options
When to Consider Non-Stimulants
Non-stimulant medications are particularly appropriate for:
- Patients with substance use concerns (lower abuse potential) 1
- Those unresponsive or incompletely responsive to stimulants 4
- Patients with comorbid conditions such as tics, anxiety, or depression 4
- Those experiencing sleep disturbances or eating problems with stimulants 4
- Situations where drug abuse or diversion is a concern 4
Monitoring and Follow-up
- Follow-up within 2-4 weeks after medication changes 1
- Monitor vital signs, particularly blood pressure and heart rate 1
- Assess for common side effects:
- Gastrointestinal disorders (most common)
- Decreased appetite
- Potential effects on sleep 3
- Regular assessment for suicidal ideation, particularly when initiating therapy 1
Special Considerations
- For patients with hepatic insufficiency, dose adjustments are required:
- Moderate impairment: Reduce to 50% of normal dose
- Severe impairment: Reduce to 25% of normal dose 2
- For patients taking strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine):
- Start at lower doses (0.5 mg/kg/day)
- Increase only if symptoms don't improve after 4 weeks 2
Non-stimulant medications, particularly atomoxetine, provide an important alternative for children with ADHD who cannot tolerate or do not respond adequately to stimulant medications, with the added benefit of potentially improving quality of life, self-esteem, and social functioning 4.