What are the potential side effects of Strattera (atomoxetine)?

Side Effects of Strattera (Atomoxetine)

Strattera causes gastrointestinal side effects (nausea, vomiting, abdominal pain, decreased appetite) in 10-18% of patients, along with cardiovascular effects (mild increases in heart rate and blood pressure), and carries a black-box warning for suicidal ideation in children and adolescents. 1, 2

Common Side Effects by Age Group

Children and Adolescents

The most frequently reported adverse effects include 1, 2:

• Gastrointestinal effects: Nausea (10%), vomiting (11%), abdominal pain (18%), decreased appetite (16%)
• Mood and behavioral changes: Mood swings (occurring in approximately 20% on BID dosing, 11% on QD dosing)
• Fatigue: Reported in 6-9% of patients
• Somnolence/sedation: Occurs more commonly with atomoxetine than with stimulants 3

Adults

Common adverse effects differ somewhat from pediatric patients 2:

• Dry mouth: 35% in poor CYP2D6 metabolizers vs 17% in extensive metabolizers
• Constipation: 11% in poor metabolizers vs 7% in extensive metabolizers
• Nausea and decreased appetite: 16% and 3% respectively
• Dizziness: 8% of patients
• Sexual dysfunction: Erectile dysfunction (21% in poor metabolizers vs 9% in extensive metabolizers), ejaculation delay/disorder (4%), decreased libido (3%) 2
• Urinary hesitation: 6% of patients 2

Serious Adverse Effects Requiring Monitoring

Cardiovascular Effects

• Mild increases in vital signs: Average increases of 1-2 beats per minute for heart rate and 1-4 mm Hg for blood pressure 1
• Clinically significant changes: 5-10% of adult patients experience heart rate changes ≥20 bpm or blood pressure changes ≥15-20 mm Hg 2
• Special warnings exist for patients with preexisting cardiovascular disease or significant cardiac abnormalities 1

Hepatotoxicity

• Risk of severe liver injury including hepatic failure 1
• Discontinue atomoxetine immediately if jaundice or clinically significant liver dysfunction develops 1
• Postmarketing data show three patients with liver-related adverse events probably related to atomoxetine 3

Psychiatric Effects

• Black-box warning for suicidal ideation in children and adolescents (but not adults) based on meta-analysis of 12 placebo-controlled trials 1, 3
• Children should be monitored closely for suicidality, clinical worsening, and unusual behavior changes, especially during the first few months of treatment or at times of dose change 1
• Risk of emergent psychotic or manic symptoms 1
• Special warnings for patients with bipolar disorder 1

Growth Effects

• Initial decreases in expected height and weight trajectories occur in the first 1-2 years of treatment 1
• Growth typically returns to expected measurements after 2-3 years on average 1
• Height and weight should be monitored regularly during treatment 2

Rare but Serious Effects

• Priapism: Erections lasting more than 4 hours require immediate medical attention due to potential for lasting damage 2
• Syncope: 3% in poor CYP2D6 metabolizers vs 1% in extensive metabolizers 1
• Severe allergic reactions: Including trouble breathing, swelling, or hives 2

CYP2D6 Metabolizer Status Impact

Approximately 7% of the population are poor CYP2D6 metabolizers, resulting in significantly higher rates of adverse effects 1:

Poor Metabolizers Experience Higher Rates Of:

• Depression: 7% vs 4% in extensive metabolizers 1
• Dry mouth: 35% vs 17% 1
• Constipation: 11% vs 7% 2
• Erectile dysfunction: 21% vs 9% 1, 2
• Insomnia: 19% vs 11% 2
• Tremor: 5% vs 1% 1, 2
• Urinary retention: 6% vs 1% 2

SSRIs can elevate serum atomoxetine levels through CYP2D6 inhibition, mimicking poor metabolizer status 1

Discontinuation Rates

• 11.3% of adults discontinued due to adverse reactions vs 3.0% on placebo 2
• Most common reasons for discontinuation in adults: Insomnia (0.9%), nausea (0.9%), chest pain (0.6%), fatigue (0.6%) 2
• Discontinuation appears well tolerated with low incidence of discontinuation-emergent adverse events 3

Critical Drug Interactions and Contraindications

• Concomitant use with MAOIs is contraindicated due to risk of serotonin syndrome 1
• Avoid combining with other serotonergic medications 4
• Use caution with medications that affect blood pressure 2

Common Pitfalls to Avoid

• Do not open, crush, or chew capsules—swallow whole; if powder contacts eyes, rinse immediately and call physician 2
• Recognize that adverse effects are dose-dependent, with higher rates at dosages >1.5 mg/kg/day 5
• Be aware that atomoxetine has slower onset (6-12 weeks) compared to stimulants, so early side effects may discourage continuation before therapeutic benefits emerge 1
• Monitor for urinary retention, particularly in adult males and poor metabolizers 2