What are the uses and dosages of norepinephrine reuptake inhibitors, such as atomoxetine (Strattera), in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and depression?

Norepinephrine Reuptake Inhibitors for ADHD Treatment

Atomoxetine (Strattera) is the primary norepinephrine reuptake inhibitor indicated for ADHD treatment with a recommended starting dose of 0.5 mg/kg/day and target dose of 1.2 mg/kg/day for children and adolescents up to 70 kg, or starting at 40 mg daily with a target of 80 mg daily for adults. 1

Mechanism and Indications

Atomoxetine is a selective norepinephrine reuptake inhibitor that works by inhibiting presynaptic norepinephrine reuptake in the prefrontal cortex. It is FDA-approved for:

• Treatment of ADHD in children, adolescents, and adults
• The only non-stimulant medication specifically approved for adult ADHD 1, 2

Unlike stimulant medications, atomoxetine:

• Has negligible risk of abuse or misuse
• Is not classified as a controlled substance
• Can provide 24-hour symptom coverage 2, 3

Dosing Guidelines

Children and Adolescents (≤70 kg):

• Initial dose: 0.5 mg/kg/day
• Target dose: 1.2 mg/kg/day
• Maximum dose: 1.4 mg/kg/day 4, 1

Adolescents (>70 kg) and Adults:

• Initial dose: 40 mg daily
• Target dose: 80 mg daily
• Maximum dose: 100 mg daily 1

Administration can be either once daily in the morning or divided into two evenly distributed doses (morning and late afternoon/early evening) 1, 2.

Special Populations and Dosing Adjustments

Dose adjustments are required for:

• Hepatic impairment
• Patients taking strong CYP2D6 inhibitors
• Patients who are CYP2D6 poor metabolizers 1

Efficacy in ADHD

Atomoxetine has demonstrated efficacy in multiple clinical trials:

• Significantly more effective than placebo in controlling ADHD symptoms
• Similar efficacy to immediate-release methylphenidate
• Less effective than extended-release methylphenidate formulations and mixed amphetamine salts 2, 5
• Effective for both short-term symptom control and long-term maintenance 6

Safety and Adverse Effects

Common Side Effects:

• In children: dyspepsia, nausea, vomiting, decreased appetite, weight loss 6
• In adults: dry mouth, insomnia, nausea, decreased appetite, constipation, dizziness 3

Important Safety Considerations:

• Black Box Warning: Increased risk of suicidal ideation in children and adolescents (0.4% vs. 0% with placebo) 1
• Requires monitoring for suicidality, clinical worsening, or unusual behavior changes
• May cause mild increases in blood pressure and heart rate
• Should be used with caution in patients with cardiovascular disorders 1, 6
• Risk of severe liver injury (rare) 2

Special Clinical Considerations

Atomoxetine may be particularly beneficial for:

1. Patients with substance use disorders or risk of substance abuse 4, 3
2. Patients with comorbid anxiety or tics 4, 7
3. Patients who experience significant sleep disturbances with stimulants 2, 7
4. Patients who need 24-hour symptom coverage 2

Switching from Stimulants to Atomoxetine

When transitioning from stimulants to atomoxetine:

• Consider a cross-tapering schedule
• Start with divided doses to minimize initial side effects
• Allow 6-8 weeks for full evaluation of efficacy
• Approximately 50% of non-responders to methylphenidate may respond to atomoxetine 7

Monitoring Recommendations

• Regular assessment of ADHD symptoms using standardized scales
• Monitor blood pressure and heart rate
• Follow-up within 2-4 weeks after medication initiation
• Regular assessment for suicidal ideation, particularly when initiating therapy 4, 1
• Monitor height and weight in pediatric patients 1, 2

Contraindications

Atomoxetine is contraindicated in patients with:

• Hypersensitivity to atomoxetine
• Use within 2 weeks of MAOI use
• Narrow-angle glaucoma
• Pheochromocytoma
• Severe cardiovascular disorders 1