Would Strattera (atomoxetine) be a suitable adjunct to Guanfacine (guanfacine) ER for a 6-year-old female patient with Attention Deficit Hyperactivity Disorder (ADHD) and suspected Pathological Demand Avoidance (PDA) tendencies, currently experiencing moderate benefits with Guanfacine ER 2mg nightly and Dextroamphetamine (dextroamphetamine) 10mg ER daily, but with concerns regarding growth suppression due to stimulant use?

Should Strattera Replace Dextroamphetamine in This 6-Year-Old?

No—switching from dextroamphetamine to Strattera (atomoxetine) is not recommended as the better strategy here. Instead, you should optimize the current guanfacine dose or add guanfacine as adjunctive therapy to the stimulant, as extended-release guanfacine is the only FDA-approved adjunctive medication with robust evidence for combination use with stimulants in children. 1, 2

Why Guanfacine Optimization Is Preferred Over Switching to Atomoxetine

FDA-Approved Combination Therapy Evidence

• Extended-release guanfacine and extended-release clonidine are the only two medications with sufficient evidence and FDA approval for adjunctive use with stimulants in ADHD treatment. 1, 2
• Atomoxetine as add-on therapy remains off-label, with only limited evidence available to support efficacy and safety when combined with stimulants. 1, 3
• The American Academy of Pediatrics explicitly states that guanfacine has achieved FDA approval for adjunctive therapy based on sufficient evidence, while atomoxetine has not. 1, 3

Growth Concerns: Atomoxetine Is Not the Solution

• Atomoxetine also causes growth delays compared to expected trajectories in the first 1-2 years of treatment, with return to expected measurements after 2-3 years on average. 1
• Decreases in height and weight were observed among those who were taller or heavier than average before atomoxetine treatment. 1
• This means switching to atomoxetine does not solve the growth suppression problem—it simply trades one growth-suppressing medication for another.

Efficacy Comparison: Stimulants Remain Superior

• Atomoxetine is significantly less effective than extended-release stimulants (effect size ~0.7 vs. ~1.0 for stimulants). 2, 4
• Since this child has demonstrated "great results for ADHD symptoms with stimulants," switching away from the most effective medication class is counterproductive. 4
• Atomoxetine requires 2-4 weeks before clinical benefits are observed, unlike stimulants which work immediately. 2

The Better Strategy: Optimize Guanfacine Dosing

Current Dose Is Suboptimal

• This 6-year-old is receiving guanfacine ER 2 mg nightly, but the recommended weight-based dosing is 0.05-0.12 mg/kg/day. 2
• For a typical 6-year-old (approximately 20-25 kg), the target dose range would be 1-3 mg daily, meaning there is room for dose escalation. 2
• Titrate guanfacine by 1 mg per week based on response and tolerability, with a maximum dose of 6-7 mg/day. 2

Guanfacine Provides "Around-the-Clock" Coverage

• Guanfacine ER provides continuous 24-hour symptom control with once-daily dosing, offering coverage during periods when stimulants wear off. 2
• This addresses the common problem of afternoon/evening rebound symptoms from stimulants. 2

Combination Therapy Allows Lower Stimulant Doses

• Adding optimized guanfacine to stimulants allows for lower stimulant dosages, potentially reducing stimulant-related adverse effects including growth suppression. 2
• This strategy maintains efficacy while minimizing the growth concerns that prompted this question. 2

Practical Implementation Algorithm

Step 1: Optimize Guanfacine First

• Increase guanfacine ER by 1 mg weekly to a target of 3-4 mg nightly (weight-based: 0.1 mg/kg). 2
• Monitor blood pressure and heart rate at each dose adjustment, as guanfacine decreases both parameters by 1-4 mmHg and 1-2 bpm. 2
• Allow 2-4 weeks at the optimized dose before assessing full therapeutic response. 2

Step 2: Consider Reducing Stimulant Dose

• Once guanfacine is optimized, attempt to reduce dextroamphetamine from 10 mg to 7.5 mg or 5 mg daily. 2
• This may maintain ADHD symptom control while reducing growth suppression risk. 2
• Monitor ADHD symptoms systematically using parent and teacher reports during this adjustment. 2

Step 3: Monitor Growth Parameters Closely

• Obtain baseline height, weight, and growth velocity before any medication changes. 1
• Plot growth on standardized growth charts every 3 months during treatment adjustments. 1
• If growth velocity normalizes with lower stimulant doses plus optimized guanfacine, continue this regimen. 1

When to Consider Atomoxetine (Rarely in This Case)

Atomoxetine Would Be Appropriate If:

• Stimulants are completely contraindicated (e.g., severe cardiac conditions, uncontrolled hypertension). 1
• Substance abuse risk is present (atomoxetine is non-controlled). 3, 4
• Comorbid tic disorders or Tourette syndrome exist (atomoxetine does not worsen tics). 4, 5
• Both stimulants AND guanfacine have failed at optimized doses. 3

Critical Atomoxetine Safety Warnings

• Black box warning for suicidal ideation: 4 out of every 1,000 patients developed suicidal thoughts in clinical trials. 6, 4
• Monitor closely for anxiety, agitation, panic attacks, irritability, hostility, aggressiveness, impulsivity, restlessness, mania, and depression. 6
• Rare but serious liver injury: obtain baseline hepatic function and monitor for itching, right upper belly pain, dark urine, yellow skin/eyes, or unexplained flu-like symptoms. 1, 6
• Cardiovascular effects: modest increases in heart rate and blood pressure (opposite of guanfacine's effects). 1, 6

Special Consideration: PDA Tendencies and Autism Evaluation

Why This Matters for Medication Choice

• Preliminary evidence suggests atomoxetine may have benefit in autism spectrum disorder with ADHD. 4, 5
• However, this child is not yet evaluated for ASD, so making medication decisions based on suspected PDA is premature. 4
• Guanfacine is particularly appropriate when ADHD co-occurs with oppositional symptoms or disruptive behaviors, which often overlap with PDA presentations. 2

Recommendation

• Proceed with guanfacine optimization as outlined above while awaiting formal ASD evaluation. 2
• If ASD is confirmed and ADHD symptoms remain inadequately controlled despite optimized guanfacine plus stimulant therapy, then atomoxetine could be reconsidered as adjunctive therapy. 3, 4

Common Pitfalls to Avoid

Don't Abruptly Stop Guanfacine

• Guanfacine must be tapered by 1 mg every 3-7 days to avoid rebound hypertension—never discontinue suddenly. 1, 2

Don't Expect Immediate Results from Dose Changes

• Guanfacine requires 2-4 weeks at the optimized dose before full therapeutic effects are observed. 2
• Premature dose escalation or medication switching due to impatience is a common error. 2

Don't Ignore Cardiovascular Monitoring

• Obtain baseline blood pressure and heart rate before guanfacine dose adjustments. 2
• When combining stimulants (which increase BP/HR) with guanfacine (which decreases BP/HR), monitor for opposing cardiovascular effects. 2

Don't Overlook Behavioral Interventions

• Medication optimization should occur alongside behavioral modification techniques, particularly for oppositional behaviors and PDA tendencies. 1, 7