Side Effects of Strattera (Atomoxetine)
The most common side effects of Strattera in children and adolescents are nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence, while adults most frequently experience constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction, and urinary hesitation. 1
Common Side Effects by Age Group
Children and Adolescents (≥5% incidence and twice placebo rate):
- Gastrointestinal: Nausea (10%), vomiting (11%), abdominal pain (18%)
- General: Fatigue (8%), decreased appetite (16%)
- Neurological: Somnolence (11%), headache (19%), dizziness (5%)
- Weight: Weight decrease (3%) 1
Adults (≥5% incidence and twice placebo rate):
- Gastrointestinal: Constipation, dry mouth, nausea
- Genitourinary: Erectile dysfunction (in males), urinary hesitation
- Neurological: Dizziness
- Metabolic: Decreased appetite 1
Critical Safety Warnings
Black Box Warning - Suicidal Ideation
All children and adolescents treated with atomoxetine must be monitored closely for suicidal ideation, clinical worsening, and unusual behavioral changes, especially during the first few months of treatment or during dose changes. Analysis of 12 placebo-controlled trials showed increased risk of suicidal ideation in pediatric patients. Notably, this risk was not observed in adult trials. 2
Cardiovascular Effects
- 5-10% of patients experience clinically significant changes in heart rate (≥20 bpm) or blood pressure (≥15-20 mmHg)
- Contraindicated in patients with preexisting cardiovascular disease or significant cardiac abnormalities
- Blood pressure and heart rate increases reverse upon discontinuation 1, 3
Psychiatric Effects
Monitor for:
- Emergent psychotic or manic symptoms
- Aggressive behavior or hostility (12.8% in young children with ASD)
- Mood swings
- Increased hyperactivity (9% in young children) 2, 4
Genitourinary Side Effects (Particularly in Males)
Male patients require explicit counseling about potential sexual and urinary side effects, as these are often underreported. 1, 5
- Urinary hesitation/retention: More common in men than women
- Erectile dysfunction: 21% in poor metabolizers vs 9% in extensive metabolizers
- Ejaculation disorders: 6% in poor metabolizers
- Priapism: Rare but documented
- Resolution: Typically occurs within 2 days of discontinuation 1, 5
CYP2D6 Poor Metabolizers - Higher Risk Profile
Approximately 7% of the population are CYP2D6 poor metabolizers who experience significantly higher plasma levels and increased adverse effects. These patients require dose adjustment and closer monitoring. 2
Increased side effects in poor metabolizers include:
- Insomnia (11% vs 6%)
- Dry mouth (35% vs 17%)
- Constipation (11% vs 7%)
- Erectile dysfunction (21% vs 9%)
- Hyperhidrosis (15% vs 7%)
- Tremor (5% vs 1%)
- Depression (7% vs 4%) 1
Time Course of Side Effects
Most adverse events appear within the first week of treatment, with median resolution times ranging from 3-53 days after discontinuation. 3
- Gastrointestinal effects: Typically resolve relatively rapidly
- Sexual side effects: More lingering course of resolution (up to 53 days median)
- Cardiovascular changes: Return to baseline upon discontinuation 3
Discontinuation Rates
- Pediatric trials: 3% discontinued due to adverse events in acute trials; 6.3% of extensive metabolizers and 11.2% of poor metabolizers in all studies
- Adult trials: 11.3% discontinued due to adverse events
- Most common reasons: Irritability, somnolence, aggression, nausea, vomiting, abdominal pain (pediatric); insomnia, nausea, chest pain, fatigue (adult) 1
Drug Interactions
Concomitant use with potent CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) significantly elevates atomoxetine levels and increases adverse effects. Dose adjustment is mandatory in these situations. 1
Clinical Pitfalls to Avoid
- Failing to screen for suicidality: Establish baseline and monitor systematically, especially in first 3 months
- Not checking cardiovascular status: Obtain baseline blood pressure and heart rate; monitor regularly
- Inadequate patient education about sexual/urinary effects: Patients rarely volunteer this information
- Ignoring CYP2D6 status: Consider genetic testing or empiric dose reduction if excessive side effects occur
- Missing drug interactions: Always review for CYP2D6 inhibitors before prescribing
Tolerability Profile
Atomoxetine is generally well-tolerated with mild to moderate, transient adverse effects in most cases. 6, 7 In autism spectrum disorder populations, atomoxetine demonstrates similar response rates to methylphenidate while inducing fewer adverse events and better tolerability. 7