What are the considerations and potential side effects for a child, adolescent, or adult with Attention Deficit Hyperactivity Disorder (ADHD) when using Strattera (atomoxetine)?

Strattera (Atomoxetine) for ADHD: Key Considerations and Side Effects

Positioning in Treatment Algorithm

Atomoxetine is FDA-approved as a second-line therapy for ADHD in children (6+ years), adolescents, and adults, with stimulants remaining first-line due to their superior effect size (1.0 vs 0.7 for atomoxetine). 1, 2 However, atomoxetine should be considered first-line in specific clinical scenarios: patients with comorbid substance use disorders, those at risk for medication diversion (particularly adolescents), patients with tic disorders or Tourette's syndrome, and those who cannot tolerate stimulants. 1, 2

Critical Safety Warning

The FDA has issued a black box warning for increased risk of suicidal ideation in children and adolescents taking atomoxetine. 3 Pooled analyses revealed a 0.4% risk of suicidal ideation in atomoxetine-treated patients versus 0% in placebo (5/1,357 vs 0/851 patients). 3 Close monitoring is mandatory, especially during the first few months of treatment or with dose changes. 4, 2

Dosing and Administration

Start atomoxetine at 0.5 mg/kg/day for children and adolescents up to 70 kg (or 40 mg/day for those over 70 kg and adults), titrating to a target dose of 1.2 mg/kg/day with a maximum of 1.4 mg/kg/day or 100 mg/day, whichever is lower. 2 Titration should occur every 7-14 days. 2

• Atomoxetine can be administered as a single daily dose (morning or evening) or split into two evenly divided doses to minimize gastrointestinal side effects. 4, 2
• The medication provides 24-hour "around-the-clock" symptom coverage without the peaks and valleys of stimulants. 2

Onset of Action and Patient Expectations

Atomoxetine has a delayed onset of therapeutic effect requiring 6-12 weeks for full benefit, unlike stimulants which work within hours. 2 This delayed response necessitates patient and family counseling about realistic expectations. Daily adherence is essential as atomoxetine requires steady-state drug levels to maintain therapeutic effect. 2

Common Side Effects

The most prominent side effects are gastrointestinal symptoms (decreased appetite, abdominal pain, nausea, vomiting), particularly if dosage is increased too rapidly. 1, 4 Other common adverse effects include:

• Initial somnolence and fatigue 1, 4
• Headache and dizziness 2
• Decreased appetite with potential growth delays in the first 1-2 years 4
• In adults: constipation, dry mouth, sexual side effects, and urinary hesitancy 3, 5

To minimize gastrointestinal symptoms, split the daily dose into morning and evening administration or administer in the evening only. 4

Cardiovascular Monitoring

Atomoxetine causes mild increases in heart rate and blood pressure that are generally clinically insignificant, but 5-10% of pediatric patients experience potentially clinically important changes. 4 Regular monitoring of vital signs is recommended throughout treatment. 4, 2 Expand the cardiac history to include Wolf-Parkinson-White syndrome, sudden death in the family, hypertrophic cardiomyopathy, and long QT syndrome before initiating treatment. 1

Growth Considerations

Atomoxetine is associated with growth delays in the first 1-2 years of treatment, with return to expected measurements after 2-3 years on average. 4 However, it causes fewer appetite and growth problems compared to stimulants. 4 Children should have height and weight monitored regularly during treatment. 3

Rare but Serious Adverse Effects

Extremely rarely, hepatitis has been associated with atomoxetine; treatment must be discontinued immediately if jaundice or clinically significant liver dysfunction develops. 4 Additionally, priapism (erections lasting >4 hours) has occurred rarely and requires immediate medical evaluation. 3

Pharmacogenetic Considerations

Approximately 7% of Caucasians and 2% of African Americans are poor CYP2D6 metabolizers, resulting in 10-fold higher drug exposure and significantly higher rates of adverse effects. 4, 2 In extensive metabolizers, atomoxetine has a plasma half-life of 5.2 hours, while in poor metabolizers it extends to 21.6 hours. 6 Potent CYP2D6 inhibitors (such as paroxetine) can convert extensive metabolizers to a poor metabolizer phenotype. 6

Special Populations

Adolescents

Before initiating atomoxetine in adolescents, assess for substance abuse symptoms. 1 Atomoxetine has no abuse potential and is not a controlled substance, making it particularly valuable when diversion is a concern. 1, 7 Consider providing medication coverage for driving hours with longer-acting formulations or late-afternoon dosing. 1

Preschool Children (Ages 4-5)

Atomoxetine is not FDA-approved for children under 6 years of age. 1 Behavior therapy should be initiated first in preschool-aged children, with medication reserved for those with inadequate response. 1

Young Children with Autism Spectrum Disorder

Recent evidence suggests atomoxetine at 1.2-1.8 mg/kg/day may be effective and well-tolerated in children aged 3-6 years with comorbid ADHD and ASD, though close monitoring remains essential. 8 In this population, 37.6% experienced adverse events, with 17.3% discontinuing treatment. 8

Discontinuation Protocol

Atomoxetine should be tapered over 1-2 weeks rather than stopped abruptly to minimize potential adverse effects. 9 There is no evidence of withdrawal syndrome or symptom rebound upon discontinuation. 10, 7 Allow a washout period of at least 1 week before initiating another non-stimulant medication. 9

When to Switch from Atomoxetine

If atomoxetine is ineffective after 6-12 weeks or poorly tolerated, consider switching to a stimulant medication (methylphenidate or amphetamine derivatives) or alternative non-stimulants like extended-release guanfacine or clonidine. 2 Atomoxetine is significantly less effective than extended-release methylphenidate formulations and extended-release mixed amphetamine salts. 7

Key Clinical Pitfalls to Avoid

• Do not expect immediate symptom improvement; counsel patients about the 6-12 week onset of action 2
• Do not increase dosage too rapidly; this significantly increases gastrointestinal side effects 4
• Do not ignore cardiovascular monitoring during treatment 4
• Do not prescribe without discussing the black box warning for suicidal ideation with families 3
• Do not open, crush, or chew capsules; if powder contacts eyes, rinse immediately and contact physician 3