What is Atomoxetine Used For?
Atomoxetine is FDA-approved for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children, adolescents, and adults. 1
Primary Indication
Atomoxetine is a selective norepinephrine reuptake inhibitor (not a stimulant) specifically indicated for treating ADHD across all age groups. 2, 1 It represents the first non-stimulant medication approved for ADHD and the first agent approved specifically for adult ADHD based on controlled trials in adults. 2, 3
How Atomoxetine Works
Mechanism: Atomoxetine selectively blocks presynaptic norepinephrine transporters, increasing synaptic noradrenaline levels throughout the brain. 2, 4
Dual neurotransmitter effect: In the prefrontal cortex specifically, where dopamine transporters are scarce, norepinephrine transporters also regulate dopamine reuptake—so atomoxetine increases both noradrenaline and dopamine in prefrontal cortex synapses. 2, 4
Clinical profile: Unlike stimulants, atomoxetine provides "around-the-clock" symptom control with slower onset of action (6-12 weeks to full effect), and carries no abuse potential or controlled substance restrictions. 4, 5
Specific Clinical Situations Where Atomoxetine is Particularly Useful
First-line consideration in certain comorbidities: 2
Substance use disorders: Atomoxetine may be regarded as the preferred first-line option when stimulants are unviable due to their dopaminergic activity in reward pathways and abuse potential. 2
Tic disorders and Tourette's syndrome: Clinical trials demonstrate that tics do not worsen under atomoxetine treatment, making it a safer choice than stimulants in these patients. 2
Comorbid anxiety disorders: Evidence supports atomoxetine's use in ADHD with comorbid anxiety, unlike stimulants which may exacerbate anxiety symptoms. 2
Autism spectrum disorder: Some evidence supports atomoxetine use in ADHD comorbid with autism spectrum disorder. 2
Disruptive behavior disorders: Atomoxetine may be considered as a first-line option in these conditions. 2
Dosing and Administration
Available as capsules (10,18,25,40,60,80, or 100 mg) and oral solution (4 mg/ml). 2, 4
Titration follows a weight-based approach with maximum recommended dosage of 1.4 mg/kg/day or 100 mg/day, whichever is lower. 2, 4
Can be administered once daily (morning or evening) or split into two divided doses. 2, 5
Evening-only dosing is an option if needed to minimize daytime side effects. 2
Critical Safety Monitoring Requirements
Black box warning for suicidal ideation: Analysis of twelve placebo-controlled trials showed increased risk of suicidal ideation in children and adolescents receiving atomoxetine. 2, 4 All children must be monitored closely for suicidality, clinical worsening, and unusual behavior changes, especially during the first few months or at dose changes. 2, 4
Cardiovascular monitoring: 2, 4
- Obtain personal and family cardiac history before initiating treatment (sudden death, cardiovascular symptoms, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, long QT syndrome). 2
- Monitor heart rate and blood pressure regularly, as atomoxetine causes mild increases (average 1-2 beats per minute for HR, 1-4 mm Hg for BP). 2, 4
- Perform ECG if risk factors are present before starting treatment. 2
Hepatotoxicity monitoring: Discontinue immediately if jaundice or clinically significant liver dysfunction develops, as rare cases of severe liver injury including hepatic failure have occurred. 4
CYP2D6 considerations: Atomoxetine is metabolized through CYP2D6; approximately 7% of the population are poor metabolizers who experience higher plasma levels and significantly increased adverse effects. 4 Some SSRIs can elevate atomoxetine levels through CYP2D6 inhibition. 2, 4
Common Adverse Effects
- Gastrointestinal: nausea (10%), vomiting (11%), abdominal pain (18%), decreased appetite (16%). 4
- Initial somnolence, particularly if dose escalated too rapidly. 2
- Growth delays in first 1-2 years with return to expected measurements after 2-3 years on average. 2, 4
- Compared to stimulants: atomoxetine shows fewer appetite and growth problems, with less frequent and less pronounced adverse effects overall than alpha-2 agonists (clonidine/guanfacine). 2