What are the common side effects of atomoxetine (Attention Deficit Hyperactivity Disorder medication)?

Common Side Effects of Atomoxetine

The most common side effects of atomoxetine in children and adolescents are gastrointestinal symptoms (decreased appetite 16%, abdominal pain 18%, nausea 10%, vomiting 11%), along with somnolence (11%), fatigue (8%), and headache (19%). 1, 2

Gastrointestinal Effects

• Decreased appetite occurs in 16% of pediatric patients, representing one of the most frequent adverse effects 2
• Abdominal pain affects 18% of children and adolescents, making it the single most common side effect 2
• Nausea occurs in 10% and vomiting in 11% of pediatric patients treated with atomoxetine 2
• These gastrointestinal symptoms are particularly prominent if the dosage is increased too rapidly 1
• Splitting the daily dose into morning and evening administration, or administering atomoxetine in the evening only, can help reduce these adverse effects 1

Neuropsychiatric Effects

• Somnolence (including sedation) occurs in 11% of pediatric patients, which is notably higher than with stimulant medications 2
• Initial somnolence is common when starting atomoxetine, particularly in the early treatment phase 1
• Fatigue affects 8% of children and adolescents treated with atomoxetine 2
• Headache occurs in 19% of patients, though this is only modestly higher than placebo (15%) 2
• Irritability is reported in 6% of pediatric patients 2

Cardiovascular Effects

• Atomoxetine causes mild increases in heart rate (1-2 beats per minute) and blood pressure (1-4 mm Hg), which are generally clinically insignificant 1
• However, 5-10% of pediatric patients experience potentially clinically important changes in heart rate (≥20 beats per minute) or blood pressure (≥15-20 mm Hg) 2
• Regular monitoring of vital signs is recommended during treatment 1

Weight and Growth Effects

• Weight decrease occurs in 3% of atomoxetine-treated children, representing a common concern 2
• Atomoxetine is linked to growth delays in the first 1-2 years of treatment, with return to expected measurements after 2-3 years on average 1
• These effects are less pronounced compared to stimulant medications 1

Metabolizer Status Impact

Poor CYP2D6 metabolizers (approximately 7% of the population) experience significantly higher rates of adverse effects due to elevated plasma levels and longer half-lives 3:

• Depression occurs in 7% of poor metabolizers versus 4% in extensive metabolizers 2
• Insomnia affects 11% of poor metabolizers versus 6% of extensive metabolizers 2
• Constipation occurs in 7% of poor metabolizers versus 4% of extensive metabolizers 2
• Tremor affects 5% of poor metabolizers versus 1% of extensive metabolizers 2
• Syncope occurs in 3% of poor metabolizers versus 1% of extensive metabolizers 2

Discontinuation Rates

• Only 3% of children and adolescents discontinue atomoxetine due to adverse reactions in acute trials, compared to 1.4% with placebo 2
• Over all studies, 6.3% of extensive metabolizers and 11.2% of poor metabolizers discontinued due to adverse reactions 2
• The most common reasons for discontinuation include irritability, somnolence, aggression, nausea, vomiting, and abdominal pain (each occurring in 0.1-0.3% of patients) 2

Important Clinical Caveats

• Atomoxetine carries an FDA black box warning for increased suicidal ideation in children and adolescents (though not in adults), requiring close monitoring especially during the first few months of treatment 1, 3
• Extremely rarely, hepatitis has been associated with atomoxetine, and treatment should be discontinued immediately if jaundice or clinically significant liver dysfunction develops 1, 3
• The majority of adverse events are mild to moderate and tend to appear early in treatment, then decline over time 4, 5
• Atomoxetine shows fewer appetite and growth problems compared to stimulants, making it advantageous in certain clinical situations 1