What are the side effects of atomoxetine (Strattera)?

Side Effects of Atomoxetine

Atomoxetine causes common gastrointestinal and neuropsychiatric side effects that are generally mild to moderate, but carries serious risks including suicidal ideation in children/adolescents, cardiovascular effects, and rare hepatotoxicity that require close monitoring. 1

Common Side Effects (≥5% incidence)

In Children and Adolescents

The most frequently reported adverse effects include: 1

• Gastrointestinal effects: Nausea (10%), vomiting (11%), abdominal pain (18%), decreased appetite (16%)
• Neurological effects: Headache (19%), somnolence (11%), dizziness (5%)
• General effects: Fatigue (8%), irritability (6%)
• Weight loss: Occurs in approximately 3% of patients 1

In Adults

Adult patients experience a somewhat different profile: 1

• Gastrointestinal: Dry mouth (21%), nausea (21%), constipation (9%), abdominal pain (7%)
• Neuropsychiatric: Insomnia (15%), dizziness (8%), somnolence (8%)
• Metabolic: Decreased appetite (16%)
• Sexual dysfunction: Erectile dysfunction (8% of males), ejaculation delay/disorder (4% of males) 1
• Autonomic: Urinary hesitation (6%), hyperhidrosis (4%) 1

Serious Adverse Effects Requiring Monitoring

Suicidal Ideation (FDA Black Box Warning)

Meta-analysis of 12 placebo-controlled trials demonstrated increased risk of suicidal ideation in children and adolescents (but not adults) treated with atomoxetine. 2, 1 Children should be monitored closely for suicidality, clinical worsening, and unusual behavior changes, especially during the first few months of treatment or at dose changes. 2

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 3
• Clinically significant changes: Approximately 5-10% of patients experience potentially important changes (≥20 bpm heart rate or ≥15-20 mm Hg blood pressure) 1
• Hypertensive crisis: Rare but documented cases exist, including in pediatric patients 4
• Monitoring requirement: Obtain cardiac history (personal and family) before initiation; monitor heart rate and blood pressure regularly 3

Hepatotoxicity (Rare but Serious)

Atomoxetine has been associated with severe liver injury, including hepatic failure presenting as: 3

• Abdominal pain
• Hepatomegaly
• Elevated transaminases
• Cholestatic jaundice

Discontinue atomoxetine immediately and do not restart if jaundice or clinically significant liver dysfunction develops. 3

Psychiatric Effects

• Behavioral activation/agitation: Can occur, particularly early in treatment 3
• Mood changes: Depression (7% in poor metabolizers vs 4% in extensive metabolizers), mood swings (2-6%) 1
• Psychotic or manic symptoms: Emergent symptoms warrant special monitoring 2

Metabolizer Status Impact

Poor CYP2D6 metabolizers (approximately 7% of population) experience significantly higher rates of adverse effects due to elevated plasma levels and prolonged half-life. 2 In this population: 1

• Insomnia: 11% (vs 6% in extensive metabolizers)
• Weight decrease: 7% (vs 4%)
• Constipation: 7% (vs 4%)
• Depression: 7% (vs 4%)
• Tremor: 5% (vs 1%)
• Syncope: 3% (vs 1%)

In adults who are poor metabolizers: 1

• Dry mouth: 35% (vs 17%)
• Erectile dysfunction: 21% (vs 9%)
• Hyperhidrosis: 15% (vs 7%)

Discontinuation Rates

• Children/adolescents: 3% discontinued in acute trials (vs 1.4% placebo); 6.3% of extensive metabolizers and 11.2% of poor metabolizers discontinued in all studies 1
• Adults: 11.3% discontinued in acute trials (vs 3.0% placebo) 1
• Most common reasons: Irritability, somnolence, aggression, nausea, vomiting, abdominal pain 1

Critical Clinical Considerations

Seizure Risk

Seizures occurred in 0.2% of pediatric patients and 0.1% of adults in clinical trials. 1 Atomoxetine was not systematically studied in patients with seizure disorders as they were excluded from trials. 1

Drug Interactions

Concomitant use with MAOIs is contraindicated due to serotonin syndrome risk. 3 CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) significantly increase atomoxetine levels and adverse effects. 1

Discontinuation Syndrome

Unlike SNRIs used for anxiety/depression, atomoxetine has a relatively low incidence of discontinuation-emergent adverse events, though gradual tapering is still recommended. 5

Growth Effects

Initial decreases in expected height and weight trajectories occur in the first 1-2 years of treatment, with return to expected measurements after 2-3 years on average. 3 This effect is most pronounced in children who were taller or heavier than average before treatment. 3