How should atomoxetine (Strattera) be dosed in children, adolescents, and adults, what are the common adverse effects and required monitoring, and what steps should be taken if the patient experiences persistent vomiting?

Atomoxetine (Strattera) Dosing, Monitoring, and Management

Dosing Guidelines

Children and Adolescents (≤70 kg)

• Start at 0.5 mg/kg/day and titrate after 7–14 days to a target dose of 1.2 mg/kg/day, with a maximum ceiling of 1.4 mg/kg/day or 100 mg/day, whichever is lower. 1
• Dose adjustments should occur every 7–14 days based on tolerability and response. 1

Adolescents (>70 kg) and Adults

• Start at 40 mg/day and titrate to a target of 1.2 mg/kg/day, not exceeding 1.4 mg/kg/day or 100 mg/day, whichever is lower. 1
• The same 7–14 day titration interval applies. 1

Administration Schedule

• Atomoxetine can be given once daily (morning or evening) or split into two evenly divided doses to reduce gastrointestinal side effects. 1, 2
• Evening dosing may be advantageous if initial somnolence occurs. 1
• Once-daily dosing provides "around-the-clock" symptom control without the peaks and valleys of stimulants. 1, 3

---

Common Adverse Effects

Gastrointestinal Effects (Most Common)

• Decreased appetite (16%), nausea (10%), vomiting (11%), and abdominal pain (18%) are the most frequently reported adverse events, particularly when doses are escalated too rapidly. 1, 3
• These effects are generally transient and resolve with continued treatment or dose adjustment. 1

Central Nervous System Effects

• Somnolence, headache, fatigue, and dizziness occur commonly, especially during initial titration. 1, 3
• Initial somnolence can be managed by switching to evening dosing or splitting the dose. 1

Cardiovascular Effects

• Modest increases in heart rate (1–2 bpm) and blood pressure (1–4 mm Hg) occur but are generally well tolerated. 3
• These effects are less pronounced than with stimulants. 1

---

Required Monitoring

Baseline Assessment

• Obtain a comprehensive cardiac history, including family history of sudden cardiac death, arrhythmias, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, and long-QT syndrome. 3
• Measure baseline blood pressure and heart rate before initiating treatment. 1

Ongoing Monitoring

• Monitor blood pressure and heart rate at each visit, particularly during dose titration. 1, 3
• Track height and weight in children and adolescents, as initial decreases in expected growth trajectories may occur in the first 1–2 years, with return to expected measurements after 2–3 years. 3
• Screen for suicidal ideation closely during the first few months of treatment or after dose changes, as the FDA has issued a black box warning for increased risk in children and adolescents (but not adults). 1, 3
• Monitor for emergent psychotic or manic symptoms, particularly in patients with or at risk for bipolar disorder. 3

Hepatic Monitoring

• Discontinue atomoxetine immediately if jaundice or clinically significant liver dysfunction develops, due to rare but serious risk of hepatic failure. 3

---

Management of Persistent Vomiting

Immediate Steps

• If vomiting persists beyond the first 1–2 weeks or is severe, reduce the dose or temporarily split the daily dose into two divided doses to improve gastrointestinal tolerability. 1
• Consider switching to evening dosing if morning administration is associated with nausea and vomiting. 1

If Vomiting Continues Despite Dose Adjustment

• Discontinue atomoxetine and consider switching to an alternative ADHD medication, such as a stimulant (methylphenidate or amphetamine derivatives) or another non-stimulant (extended-release guanfacine or clonidine). 1
• Persistent vomiting (11% incidence) is a recognized adverse effect that may not resolve with continued treatment. 3

Supportive Measures

• Ensure adequate hydration and consider anti-emetic support if vomiting is severe enough to cause dehydration or electrolyte imbalance. (General medical knowledge)
• Rule out other causes of vomiting, including gastrointestinal illness or drug interactions. (General medical knowledge)

---

Special Considerations

CYP2D6 Poor Metabolizers

• Approximately 7% of Caucasians and 2% of African Americans are poor CYP2D6 metabolizers, resulting in 10-fold higher drug exposure and a half-life of approximately 24 hours. 1, 3
• Poor metabolizers experience significantly higher rates of adverse effects, including depression (7% vs. 4%), syncope (3% vs. 1%), dry mouth (35% vs. 17%), and erectile dysfunction (21% vs. 9%). 3
• Consider dose reduction in patients with known poor metabolizer status or those experiencing excessive adverse effects. 1

Drug Interactions

• Concomitant use with MAOIs is contraindicated due to risk of serotonin syndrome. 3
• Some SSRIs (e.g., paroxetine, fluoxetine) inhibit CYP2D6 and can elevate atomoxetine levels, potentially requiring dose adjustment. 3
• Lorazepam does not interact with atomoxetine because it is metabolized by glucuronidation, not CYP450 enzymes, making it safe for co-administration in acute agitation. 3

Onset of Action

• Full therapeutic effects require 6–12 weeks, so patients and families must be counseled about this delayed timeline to prevent premature discontinuation. 1, 3
• Assess response only after an adequate trial period of 6–12 weeks at the target dose. 1

---

Discontinuation

• Atomoxetine can be stopped abruptly without tapering, unlike alpha-2 agonists (clonidine, guanfacine), which require gradual discontinuation to avoid rebound hypertension. 1
• Common adverse effects such as decreased appetite, nausea, and somnolence will resolve after stopping. 1

---

Clinical Pearls

When to Use Atomoxetine as First-Line

• Atomoxetine is preferred over stimulants in patients with comorbid substance use disorders, tic disorders, Tourette's syndrome, anxiety disorders, or autism spectrum disorder with ADHD. 1
• In patients with prominent anxiety, agitation, or racing thoughts, atomoxetine should be used first-line because stimulants may exacerbate these symptoms and lose their usual 70–80% response advantage. 1

Combination Strategies

• If ADHD symptoms improve but anxiety persists, adding an SSRI (e.g., fluoxetine or sertraline) is safe and effective, though caution is required with CYP2D6-inhibiting SSRIs. 1
• For residual hyperactivity, aggression, or sleep disturbances, add clonidine 0.05 mg at bedtime, titrating slowly and never exceeding 0.3 mg/day. 1

Abuse Potential

• Atomoxetine has negligible abuse potential and is not a controlled substance, making it ideal for patients at risk of substance misuse or diversion. 3, 2, 4